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Colorectal cancer (CRC) is a major cause of cancer-related deaths globally. While treatment advancements have improved survival rates, primarily through targeted therapies based on KRAS, NRAS, and BRAF mutations, personalized treatment strategies for CRC remain limited. Immunotherapy, mainly immune checkpoint blockade, has shown efficacy in various cancers but is effective in only a small subset of patients with CRC with deficient mismatch repair (dMMR) proteins or high microsatellite instability (MSI). Recent research has challenged the notion that CRC is immunologically inert, revealing subsets with high immunogenicity and diverse lymphocytic infiltration. Identifying precise biomarkers beyond dMMR and MSI is crucial to expanding immunotherapy benefits. Hence, exploration has extended to various biomarker sources, such as the tumor microenvironment, genomic markers, and gut microbiota. Recent studies have introduced a novel classification system, consensus molecular subtypes, that aids in identifying patients with CRC with an immunogenic profile. These findings underscore the necessity of moving beyond single biomarkers and toward a comprehensive understanding of the immunological landscape in CRC, facilitating the development of more effective, personalized therapies.

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Breast cancer encompasses a diverse array of subtypes, each exhibiting distinct clinical characteristics and treatment responses. Unraveling the underlying regulatory mechanisms that govern gene expression patterns in these subtypes is essential for advancing our understanding of breast cancer biology. Gene co-expression networks (GCNs) help us identify groups of genes that work in coordination. Previous research has revealed a marked reduction in the interaction of genes located on different chromosomes within GCNs for breast cancer, as well as for lung, kidney, and hematopoietic cancers. However, the reasons behind why genes on the same chromosome often co-express remain unclear. In this study, we investigate the role of transcription factors in shaping gene co-expression networks within the four main breast cancer subtypes: Luminal A, Luminal B, HER2+, and Basal, along with normal breast tissue. We identify communities within each GCN and calculate the transcription factors that may regulate these communities, comparing the results across different phenotypes. Our findings indicate that, in general, regulatory behavior is to a large extent similar among breast cancer molecular subtypes and even in healthy networks. This suggests that transcription factor motif usage does not fully determine long-range co-expression patterns. Specific transcription factor motifs, such as CCGGAAG, appear frequently across all phenotypes, even involving multiple highly connected transcription factors. Additionally, certain transcription factors exhibit unique actions in specific subtypes but with limited influence. Our research demonstrates that the loss of inter-chromosomal co-expression is not solely attributable to transcription factor regulation. Although the exact mechanism responsible for this phenomenon remains elusive, this work contributes to a better understanding of gene expression regulatory programs in breast cancer.

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BACKGROUND: Colorectal cancer is a complex disease with high mortality rates. Over time, the treatment of metastatic colorectal cancer (mCRC) has gradually improved due to the development of modern chemotherapy and targeted therapy regimens. However, due to the inherent heterogeneity of this condition, identifying reliable predictive biomarkers for targeted therapies remains challenging. A recent promising classification system-the consensus molecular subtype (CMS) system-offers the potential to categorize mCRC patients based on their unique biological and molecular characteristics. Four distinct CMS categories have been defined: immune (CMS1), canonical (CMS2), metabolic (CMS3), and mesenchymal (CMS4). Nevertheless, there is currently no standardized protocol for accurately classifying patients into CMS categories. To address this challenge, reverse transcription polymerase chain reaction (RT-qPCR) and next-generation genomic sequencing (NGS) techniques may hold promise for precisely classifying mCRC patients into their CMSs. AIM: To investigate if mCRC patients can be classified into CMS categories using a standardized molecular biology workflow. METHODS: This observational study was conducted at the University of Chile Clinical Hospital and included patients with unresectable mCRC who were undergoing systemic treatment with chemotherapy and/or targeted therapy. Molecular biology techniques were employed to analyse primary tumour samples from these patients. RT-qPCR was utilized to assess the expression of genes associated with fibrosis (TGF-ß and ß-catenin) and cell growth pathways (c-MYC). NGS using a 25-gene panel (TumorSec) was performed to identify specific genomic mutations. The patients were then classified into one of the four CMS categories according to the clinical consensus of a Tumour Board. Informed consent was obtained from all the patients prior to their participation in this study. All techniques were conducted at University of Chile. RESULTS: Twenty-six patients were studied with the techniques and then evaluated by the Tumour Board to determine the specific CMS. Among them, 23% (n = 6), 19% (n = 5), 31% (n = 8), and 19% (n = 5) were classified as CMS1, CMS2, CMS3, and CMS4, respectively. Additionally, 8% of patients (n = 2) could not be classified into any of the four CMS categories. The median overall survival of the total sample was 28 mo, and for CMS1, CMS2, CMS3 and CMS4 it was 11, 20, 30 and 45 mo respectively, with no statistically significant differences between groups. CONCLUSION: A molecular biology workflow and clinical consensus analysis can be used to accurately classify mCRC patients. This classification process, which divides patients into the four CMS categories, holds significant potential for improving research strategies and targeted therapies tailored to the specific characteristics of mCRC.

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AIM: This study aimed to examine the prognostic significance of the KI-67 proliferation index, especially in breast cancer (BC) patients without HER-2 expression and no nodal involvement. MATERIAL AND METHODS: The database of hormone-receptor-positive patients who underwent surgery for BC in our Surgical Oncology Clinic between 2008 and 2020 was retrospectively reviewed and recorded. Patients were categorized based on their KI-67 level, considering the cutoff value of 20%. RESULTS: Our study revealed that tumors with high KI-67 levels were more likely to have a more advanced histological grade (p = 0.00) and size (p = 0.038). In the univariant analysis, KI-67 level was effective on overall survival (p = 0.044) and disease-free survival (p = 0.048). However, we found that there was no independent prognostic factor in the multivariant analysis. CONCLUSION: Although the Ki-67 proliferation index does not yet have an agreed threshold value and scoring methodology, it can also be used to determine prognosis and evaluate treatment response in some patients.

OBJETIVO: Este estudio tuvo como objetivo examinar la importancia pronóstica del índice de proliferación KI-67, especialmente en pacientes con cáncer de mama sin expresión de HER-2 y sin compromiso ganglionar. MATERIAL Y MÉTODOS: Se revisó y registró retrospectivamente la base de datos de pacientes con receptores hormonales positivos intervenidas de cáncer de mama en nuestra Clínica de Oncología Quirúrgica entre 2008 y 2020. Las pacientes fueron categorizadas de acuerdo con su nivel de KI-67, considerando el valor de corte del 20%. RESULTADOS: Nuestro estudio reveló que los tumores con valores elevados de KI-67 eran más propensos a tener un grado histológico (p = 0.00) y un tamaño (p = 0.038) más avanzados. En el análisis univariado, el nivel de KI-67 fue efectivo sobre la supervivencia global (p = 0.044) y la supervivencia libre de enfermedad (p = 0.048). Sin embargo, encontramos que no había ningún factor pronóstico independiente en el análisis multivariante. CONCLUSIONES: Aunque el índice de proliferación Ki-67 aún no tiene un valor de umbral acordado ni una metodología de puntuación, también se puede utilizar para determinar el pronóstico y evaluar la respuesta al tratamiento en algunas pacientes.

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Prostate cancer (PCa) is one of cancer with of the highest incidence and mortality worldwide. Current disease prognostic markers do not differentiate aggressive from indolent PCa with sufficient certainty, and characterization by molecular subtypes has been sought to allow a better classification. TMPRSS2-ERG, SPOP, FOXA1, and IDH1 molecular subtypes have been described, but the association of these subtypes with prognosis in PCa is unclear; their frequency in Colombian patients is also unknown. Formalin-fixed and paraffin-embedded samples of radical prostatectomy from 112 patients with PCa were used. The TMPRSS2-ERG subtype was assessed with fluorescent in situ hybridization. The mutations in SPOP, FOXA1, and IDH1 in hot-spot regions were evaluated using Sanger sequencing. Fusion was detected in 71 patients (63.4%). No statistically significant differences were found between the state of fusion and the variables analyzed. In the 41 fusion-negative cases (36.6%), two patients (4.9%) had missense mutations in SPOP (p.F102C and p.F133L), representing a 1.8% of the overall cohort. The low frequency of this subtype in Colombians could be explained by the reported variability in the frequency of these mutations according to the population (5%-20%). No mutations were found in FOXA1 in the cases analyzed. The synonym SNP rs11554137 IDH1105GGT was found in tumor tissue but not in the normal tissue in one case. A larger cohort of Colombian PCa patients is needed for future studies to validate these findings and gain a better understanding of the molecular profile of this cancer in our population and if there are any differences by Colombian regions.

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Molecular profile of breast cancer in Latin-American women was studied in five countries: Argentina, Brazil, Chile, Mexico, and Uruguay. Data about socioeconomic characteristics, risk factors, prognostic factors, and molecular subtypes were described, and the 60-month overall cumulative survival probabilities (OS) were estimated. From 2011 to 2013, 1,300 eligible Latin-American women 18 years or older, with a diagnosis of breast cancer in clinical stage II or III, and performance status ≦̸1 were invited to participate in a prospective cohort study. Face-to-face interviews were conducted, and clinical and outcome data, including death, were extracted from medical records. Unadjusted associations were evaluated by Chi-squared and Fisher's exact tests and the OS by Kaplan-Meier method. Log-rank test was used to determine differences between cumulative probability curves. Multivariable adjustment was carried out by entering potential confounders in the Cox regression model. The OS at 60 months was 83.9%. Multivariable-adjusted death hazard differences were found for women living in Argentina (2.27), Chile (1.95), and Uruguay (2.42) compared with Mexican women, for older (≥60 years) (1.84) compared with younger (≤40 years) women, for basal-like subtype (5.8), luminal B (2.43), and HER2-enriched (2.52) compared with luminal A subtype, and for tumor clinical stages IIB (1.91), IIIA (3.54), and IIIB (3.94) compared with stage IIA women. OS was associated with country of residence, PAM50 intrinsic subtype, age, and tumor stage at diagnosis. While the latter is known to be influenced by access to care, including cancer screening, timely diagnosis and treatment, including access to more effective treatment protocols, it may also influence epigenetic changes that, potentially, impact molecular subtypes. Data derived from heretofore understudied populations with unique geographic ancestry and sociocultural experiences are critical to furthering our understanding of this complexity.

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Resumen ANTECEDENTES: El cáncer de mama es la principal neoplasia en incidencia y mortalidad en mujeres. Los subtipos moleculares: luminal A, luminal B, HER2 y triple negativo tienen un pronóstico y tasas de supervivencia diferentes. En la bibliografía está demostrada la estrecha asociación entre los factores estímulo estrogénicos y el cáncer de mama en general, aunque las diferencias no son claras debido a los subtipos moleculares. OBJETIVO: Revisar la bibliografía reciente y describir la relación entre los subtipos moleculares del cáncer de mama y los factores reproductivos. METODOLOGÍA: Búsqueda en las bases de datos PubMed y LILACS con los términos MeSH y DeCS: neoplasias de la mama, subtipos moleculares, factores de riesgo, factores reproductivos. Se buscó la asociación entre los antecedentes de paridad, edad al primer embarazo y el antecedente de lactancia materna con los subtipos moleculares de cáncer de mama: luminal A, luminal B y HER2. RESULTADOS: Se obtuvieron 366 artículos y se eliminaron 352 por: duplicidad en títulos y resúmenes, sin pertinencia para el tema, protocolos de investigación que no estudiaran la asociación entre factores estímulo estrogénicos con los subtipos moleculares de cáncer de mama. Al final, el análisis se hizo con 14 artículos. CONCLUSIONES: Los tumores con receptores hormonales positivos se asociaron con: edad mayor al primer embarazo, mayor tiempo entre la menarquia y el primer embarazo a término y edad avanzada en el último embarazo. Factores protectores para tumores luminales y HER2 puro: lactancia materna y multiparidad.

Abstract BACKGROUND: Breast cancer represents the main neoplasia in incidence and mortality in women, it can be divided into molecular subtypes (luminal A, luminal B, HER2 and triple negative) having a differential prognosis and survival rates. There is literature that demonstrates the strong association between estrogenic stimulating factors and breast cancer, but the existing differences by molecular subtypes are not clear. OBJECTIVE: To review the recent literature and describe the relationship found between molecular subtypes of breast cancer and estrogenic stimulating factors. METHODOLOGY: Search in the PubMed and LILACS databases with the MeSH and DeCS terms: breast neoplasms, molecular subtypes, risk factors, reproductive factors, looking for the association between the antecedents of parity, age at first pregnancy and history of breastfeeding with molecular subtypes of breast cancer (luminal A, luminal B and HER2). RESULTS: A total of 366 results were obtained, excluding 352 articles when evaluating duplicity, titles and abstracts, articles without relevance to the topic, research protocols and articles that did not study the association of estrogenic stimulating factors with molecular subtypes of breast cancer, resulting in 14 articles. CONCLUSIONS: Hormone receptor-positive tumors were found to be associated with older age at first pregnancy, longer time between menarche and first term pregnancy and older age at last pregnancy. Breastfeeding and multiparity were found as protective factors for luminal tumors and pure Her2.

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INTRODUCTION: Young women under 30 years with breast cancer (BC) are an emerging challenge. The purpose is to identify prognostic factors for survival in young women under 30 years of age with BC. MATERIAL AND METHODS: A retrospective cohort study was conducted among women younger than or equal to 40 years with BC and who were treated at the State Cancer Center during the period 2012-2017. Overall survival was assessed using the Kaplan-Meier method and the log-rank test. Univariate and multivariate analysis assessed survival predictors using Cox proportional hazards regression model. RESULTS: 282 young women were included. The >30-year-old subgroup showed a significant association with excess weight (P = .002) compared to the <30-year-old group. The <30-year-old subgroup showed a poor overall survival (56.7%), as well as highly significant values in advanced clinical stages, metastatic nodules, metastasis, and neoadjuvant therapy (P < .001). In Model 3 of the multivariate analysis, age <30 years (HR = 3.0; 95% CI 1.1 to 8.6), triple negative subtype (HR = 2.6; 95% CI 1.1 to 6.0), tumor size >5 cm HR = 2.3; 95% CI 1.03 to 5.1), and advanced clinical stages (HR = 6.6 95% CI 1.3 to 35.5) persisted as predictors. CONCLUSIONS: Being very young (<30 years) is a predictor for limited survival compared to the age of 30-40 years, as well as the tumor covariates for a worse prognosis: triple negative subtype, advanced stages, positive lymph nodes, and distant metastases in liver.

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Abstract Background: Whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) are two treatment modalities commonly utilized to treat brain metastases (BMs). Aim: The purpose of this study is to analyse retrospectively the local control and survival of patients with BMs of breast cancer (BC) treated via radiosurgery using Volumetric Modulated Arc Therapy (VMAT-RS). Methods: 18 patients with 41 BMs of BC and treated by VMAT-RS were studied. They were classified according to the molecular subtype of BC and the modified breast graded prognostic assessment -GPA- index. Patients presented 1-4 BMs, which were treated with 5 non-coplanar VMAT arcs. The spatial distribution of BMs, the influence of receptor status on the location of the lesions and survival assessed via the Kaplan-Meier model were analyzed. Results: The median survival time (MST) was 19.7 months. Statistically significant differences were determined in the MST according to the Karnofsky performance status (p= 0.02) and the HER2 status (p= 0.004), being more prolonged in the HER2+ patients. Finally, our results showed that the cerebellum is the predominant site of breast cancer BMs, and also suggested that HER2+BMs had a predilection for some structures of the posterior circulation, such as the cerebellum, brainstem and occipital lobes (p= 0.048). Conclusions: The VMAT-RS is a technique with an overall survival comparable to other radiosurgery techniques. The baseline situation at the time of treatment, the modified breast-GPA and the molecular subtypes, are factors that significantly influence patient survival.

Resumen Antecedentes: La radioterapia holocraneal (WBRT) y la radiocirugía estereotáctica (SRS) son dos modalidades de tratamiento comúnmente empleados para el tratamiento de las metástasis cerebrales (BMs). Objetivo: El propósito de este estudio es analizar de forma retrospectiva el control local y la supervivencia de los pacientes con BMs de cáncer de mama (BC) tratados mediante radiocirugía empleando arcoterapia volumétrica modulada (VMAT-RS). Métodos: Se analizaron 18 pacientes con 41 BMs de BC tratados mediante VMAT-RS. Se clasificaron según el subtipo molecular de BC y el GPA (Graded Prognostic Assessment) modificado de cáncer de mama. Los pacientes presentaron de 1-4 BMs, las cuales fueron tratadas con 5 arcos VMAT no coplanares. Se analizó la distribución espacial de las BMs, la influencia del status del receptor en la localización de las lesiones y la supervivencia evaluada mediante el modelo de Kaplan-Meier. Resultados: La mediana del tiempo de supervivencia (MST) fue de 19.7 meses. Se hallaron diferencias estadísticamente significativas en el MST según el índice de Karnofsky (p= 0.02) y el status de HER2 (p= 0.004), siendo más prolongado en las pacientes HER2+. Por último, nuestros resultados mostraron que el cerebelo es el lugar predominante de las BMs de cáncer de mama, y también sugirieron que las BMs HER2+ presentaban una predilección por algunas estructuras de la circulación posterior, como el cerebelo, el tronco cerebral y los lóbulos occipitales (p= 0.048). Conclusiones: VMAT-RS es una técnica con una supervivencia global comparable a otras técnicas de radiocirugía. La situación basal en el momento del tratamiento, el GPA modificado de cáncer de mama así como los subtipos moleculares de cáncer de mama, son factores que influyen de forma significativa en la supervivencia de los pacientes.

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BACKGROUND: Ovarian cancer is one of the most common malignancies often resulting in a poor prognosis. 5-methylcytosine (m5C) is a common epigenetic modification with roles in eukaryotes. However, the expression and function of m5C regulatory factors in ovarian cancer remained unclear. RESULTS: Two molecular subtypes with different prognostic and clinicopathological features were identified based on m5C regulatory factors. Meanwhile, functional annotation showed that in the two subtypes, 452 differentially expressed genes were significantly related to the malignant progression of ovarian cancer. Subsequently, four m5C genes were screened to construct a risk marker predictive of overall survival and indicative of clinicopathological features of ovarian cancer, also the robustness of the risk marker was verified in external dataset and internal validation set. multifactorial cox regression analysis and nomogram demonstrated that risk score was an independent prognostic factor for ovarian cancer prognosis. CONCLUSION: In conclusion, our results revealed that m5C-related genes play a critical role in tumor progression in ovarian cancer. Further detection of m5C methylation could provide a novel targeted therapy for treating ovarian cancer.

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BACKGROUND: Colorectal cancer (CRC) is among the deadliest cancers, wherein early dissemination of tumor cells, and consequently, metastasis formation, are the main causes of mortality and poor prognosis. Cofilin-1 (CFL-1) and its modulators, LIMK1/SSH1, play key roles in mediating the invasiveness by driving actin cytoskeleton reorganization in various cancer types. However, their clinical significance and prognostic value in CRC has not been fully explored. Here, we evaluated the clinical contribution of these actin regulators according to TNM and consensus molecular subtypes (CMSs) classification. METHODS: CFL-1, LIMK1 and SSH1 mRNA/protein levels were assessed by real-time PCR and immunohistochemical analyses using normal adjacent and tumor tissues obtained from a clinical cohort of CRC patients. The expression levels of these proteins were associated with clinicopathological features by using the chi square test. In addition, using RNA-Seq data of CRC patients from The Cancer Genome Atlas (TCGA) database, we determine how these actin regulators are expressed and distributed according to TNM and CMSs classification. Based on gene expression profiling, Kaplan-Meier survival analysis was used to evaluated overall survival. RESULTS: Bioinformatic analysis revealed that LIMK1 expression was upregulated in all tumor stages. Patients with high levels of LIMK1 demonstrated significantly lower overall survival rates and exhibited greater lymph node metastatic potential in a clinical cohort. In contrast, CFL-1 and SSH1 have expression downregulated in all tumor stages. However, immunohistochemical analyses showed that patients with high protein levels of CFL-1 and SSH1 exhibited greater lymph node metastatic potential and greater depth of local invasion. In addition, using the CMSs classification to evaluate different biological phenotypes of CRC, we observed that LIMK1 and SSH1 genes are upregulated in immune (CMS1) and mesenchymal (CMS4) subtypes. However, patients with high levels of LIMK1 also demonstrated significantly lower overall survival rates in canonical (CMS2), and metabolic (CMS3) subtypes. CONCLUSIONS: We demonstrated that CFL-1 and its modulators, LIMK1/SSH1, are differentially expressed and associated with lymph node metastasis in CRC. Finally, this expression profile may be useful to predict patients with aggressive signatures, particularly, the immune and mesenchymal subtypes of CRC.

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The diagnosis of juvenile myelomonocytic leukaemia (JMML) is based on clinical, laboratory and molecular features but immunophenotyping [multiparametric flow cytometry (MFC)] has not been used routinely. In the present study, we describe the flow cytometric features at diagnosis with special attention to the distribution of monocytic subsets and the relation between MFC and molecular subgroups. MFC was performed with an eight-colour platform based on Euroflow. We studied 33 JMML cases. CD34+ /CD117+ /CD13+ cells >2% was found in 25 cases, and 51·5% presented an aberrant expression of CD7. A decrease of CD34+ /CD19+ /CD10+ cells was seen in eight cases and in four they were absent. The granulocytic population had a decreased side scatter in 29 cases. Bone marrow monocytic precursors were increased in 28 patients, with a decrease in classical monocytes (median 80·7%) and increase in CD16+ (intermediate and non-classical). A more pronounced increase in myeloid CD34+ cells was seen in patients with Neurofibromatosis type 1 (NF1) and tyrosine-protein phosphatase non-receptor type 11 (PTPN11), with aberrant CD7 expression in four of six and 10/12 patients respectively. Thus, JMML shows an immunophenotypic profile similar to myelodysplastic syndromes, and a different monocyte subset distribution when compared with chronic MML. MFC proved to be an important diagnostic tool that can help in differential diagnosis with other clonal diseases with monocytosis.

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Background: Whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) are two treatment modalities commonly utilized to treat brain metastases (BMs). Aim: The purpose of this study is to analyse retrospectively the local control and survival of patients with BMs of breast cancer (BC) treated via radiosurgery using Volumetric Modulated Arc Therapy (VMAT-RS). Methods: 18 patients with 41 BMs of BC and treated by VMAT-RS were studied. They were classified according to the molecular subtype of BC and the modified breast graded prognostic assessment -GPA- index. Patients presented 1-4 BMs, which were treated with 5 non-coplanar VMAT arcs. The spatial distribution of BMs, the influence of receptor status on the location of the lesions and survival assessed via the Kaplan-Meier model were analyzed. Results: The median survival time (MST) was 19.7 months. Statistically significant differences were determined in the MST according to the Karnofsky performance status (p= 0.02) and the HER2 status (p= 0.004), being more prolonged in the HER2+ patients. Finally, our results showed that the cerebellum is the predominant site of breast cancer BMs, and also suggested that HER2+BMs had a predilection for some structures of the posterior circulation, such as the cerebellum, brainstem and occipital lobes (p= 0.048). Conclusions: The VMAT-RS is a technique with an overall survival comparable to other radiosurgery techniques. The baseline situation at the time of treatment, the modified breast-GPA and the molecular subtypes, are factors that significantly influence patient survival.

Antecedentes: La radioterapia holocraneal (WBRT) y la radiocirugía estereotáctica (SRS) son dos modalidades de tratamiento comúnmente empleados para el tratamiento de las metástasis cerebrales (BMs). Objetivo: El propósito de este estudio es analizar de forma retrospectiva el control local y la supervivencia de los pacientes con BMs de cáncer de mama (BC) tratados mediante radiocirugía empleando arcoterapia volumétrica modulada (VMAT-RS). Métodos: Se analizaron 18 pacientes con 41 BMs de BC tratados mediante VMAT-RS. Se clasificaron según el subtipo molecular de BC y el GPA (Graded Prognostic Assessment) modificado de cáncer de mama. Los pacientes presentaron de 1-4 BMs, las cuales fueron tratadas con 5 arcos VMAT no coplanares. Se analizó la distribución espacial de las BMs, la influencia del status del receptor en la localización de las lesiones y la supervivencia evaluada mediante el modelo de Kaplan-Meier. Resultados: La mediana del tiempo de supervivencia (MST) fue de 19.7 meses. Se hallaron diferencias estadísticamente significativas en el MST según el índice de Karnofsky (p= 0.02) y el status de HER2 (p= 0.004), siendo más prolongado en las pacientes HER2+. Por último, nuestros resultados mostraron que el cerebelo es el lugar predominante de las BMs de cáncer de mama, y también sugirieron que las BMs HER2+ presentaban una predilección por algunas estructuras de la circulación posterior, como el cerebelo, el tronco cerebral y los lóbulos occipitales (p= 0.048). Conclusiones: VMAT-RS es una técnica con una supervivencia global comparable a otras técnicas de radiocirugía. La situación basal en el momento del tratamiento, el GPA modificado de cáncer de mama así como los subtipos moleculares de cáncer de mama, son factores que influyen de forma significativa en la supervivencia de los pacientes.

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OBJECTIVE: To compare the intratumoral T2 signal intensity on MRI and histopathological and molecular expression of biomarkers of aggressiveness (histological grade, hormonal status, HER2, and Ki-67). METHODS: This retrospective study included all women with invasive breast cancer undergoing MRI from January 2014 to October 2016. The intratumoral T2 signal as interpreted at consensus by two radiologists was compared to histopathological and molecular prognostic factors from the surgical specimen. Statistical analyses used Pearson χ 2 test with a confidence level of 95% (P ≤ 0.05). RESULTS: Fifty patients with 50 lesions met study criteria (mean age 65.8 ± 13.5 years). Mean lesion size was 28 mm ± 15.7 mm (range, 15 to 76 mm). Cancer types were invasive ductal (35/50, 70%), invasive lobular (10/50, 20%), and mixed (5/50, 10%). Most lesions were histological grade 1 or 2 (41/50, 82%) and luminal type (45/50, 90%). On T2 images, lesions were hypointense in 62% (31/50), isointense in 20% (10/50), and hyperintense in 18% (9/50) of cases. Among hypointense lesions, 94% (29/31) were low or intermediate grade tumors (P = 0.02), low HER2 overexpression (30/31, 97%) (P = 0.005), and high ER status (30/31, 97%) (P = 0.006), high PR (26/31, 84%) (P = 0.02), and low incidence of necrosis (2/31, 6%). The difference in Ki-67 tumoral expression between groups was not significant. CONCLUSION: Intratumoral T2 hypointensity in invasive breast cancer is associated with better prognostic tumors, such as histological low-grade high hormone receptor status.

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BACKGROUND: Ovarian cancer is one of the most common malignancies often resulting in a poor prognosis. 5-methylcytosine (m5C) is a common epigenetic modification with roles in eukaryotes. However, the expression and function of m5C regulatory factors in ovarian cancer remained unclear. RESULTS: Two molecular subtypes with different prognostic and clinicopathological features were identified based on m5C regulatory factors. Meanwhile, functional annotation showed that in the two subtypes, 452 differentially expressed genes were significantly related to the malignant progression of ovarian cancer. Subsequently, four m5C genes were screened to construct a risk marker predictive of overall survival and indicative of clinicopathological features of ovarian cancer, also the robustness of the risk marker was verified in external dataset and internal validation set. multifactorial cox regression analysis and nomogram demonstrated that risk score was an independent prognostic factor for ovarian cancer prognosis. CONCLUSIONS: In conclusion, our results revealed that m5C-related genes play a critical role in tumor progression in ovarian cancer. Further detection of m5C methylation could provide a novel targeted therapy for treating ovarian cancer.

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Studies have suggested a potential role of somatic mitochondrial mutations in cancer development. To analyze the landscape of somatic mitochondrial mutation in breast cancer and to determine whether mitochondrial DNA (mtDNA) mutational burden is correlated with overall survival (OS), we sequenced whole mtDNA from 92 matched-paired primary breast tumors and peripheral blood. A total of 324 germline variants and 173 somatic mutations were found in the tumors. The most common germline allele was 663G (12S), showing lower heteroplasmy levels in peripheral blood lymphocytes than in their matched tumors, even reaching homoplasmic status in several cases. The heteroplasmy load was higher in tumors than in their paired normal tissues. Somatic mtDNA mutations were found in 73.9% of breast tumors; 59% of these mutations were located in the coding region (66.7% non-synonymous and 33.3% synonymous). Although the CO1 gene presented the highest number of mutations, tRNA genes (T,C, and W), rRNA 12S, and CO1 and ATP6 exhibited the highest mutation rates. No specific mtDNA mutational profile was associated with molecular subtypes of breast cancer, and we found no correlation between mtDNA mutational burden and OS. Future investigations will provide insight into the molecular mechanisms through which mtDNA mutations and heteroplasmy shifting contribute to breast cancer development.

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RESUMENObjetivo: Determinar el tipo molecular más común de CM en el Hospital Metropolitano. Metodología: Se realizó un estudio descriptivo, retrospectivo, en el cual se revisaron los informes histopatológicos de todos los casos de cáncer de mama diagnosticados desde el 01 de enero del 2016 al 31 de diciembre del 2019, teniendo en cuenta los datos inmunohistoquímicos para su clasificación. En el periodo estudiado se evidenció un total de 276 casos correspondientes a cáncer de mama, posterior a la aplicación de los criterios de inclusión se analizaron los datos de 147 pacientes. Resultados: La media anual de casos nuevos fue de 40 ± 6. La media de edad al diagnóstico fue de 60.9 ± 13 años. La mayoría de pacientes están en el rango de edad de 40 a 69 años con 101 casos (69%). La mayoría de casos fue de tipo Luminal B con un total de 85 casos, lo cual corresponde al 54%, la minoría fueron de tipo triple negativo con 11 casos (7%). La mayor parte de casos (71%) tienen elevada profileración tumoral determinada por el valor de Ki-67. Conclusiones: El subtipo molecular de cáncer de mama más común es el Luminal B, y el menos frecuente es el triple negativo. La mayoría de casos tienen alta proliferación determinada por el valor de Ki-67

ABSTRACTObjective: To determine the most common molecular type of breast cancer in the Hospital Metropolitano. Methodology: This was a retrospective descriptive study, in which the histopathological reports of all breast cancer cases diagnosed from January 1, 2016 to December 31, 2019 were reviewed, taking into account immunohistochemical data for classification. In the period studied, a total of 276 cases corresponding to breast cancer were evidenced, after clas-sifying individual criterias, data from 147 patients were analyzed. Results: The annual average of new cases was 40 ± 6. The average age at diagnosis was 60.9 ± 13 years. A large number of patients are in the age range of 40 to 69 years with 101 cases (69%). More than a half were Luminal B type with a total of 85 cases which corresponds to 54%, the minority were triple negative type with 11 cases (7%). The predominant number of cases (71%) have high tumor profiling determined by Ki-67. Conclusions: In this retrospective study we found that the most common molecular subtype of breast cancer is Luminal B, and the least frequent is triple negative. The results also demonstrate that most of the cases have high proliferation determined the value of Ki-67

Assuntos

RESUMO

Breast carcinomas are characterized by anomalous gene regulatory programs. As is well-known, gene expression programs are able to shape phenotypes. Hence, the understanding of gene co-expression may shed light on the underlying mechanisms behind the transcriptional regulatory programs affecting tumor development and evolution. For instance, in breast cancer, there is a clear loss of inter-chromosomal (trans-) co-expression, compared with healthy tissue. At the same time cis- (intra-chromosomal) interactions are favored in breast tumors. In order to have a deeper understanding of regulatory phenomena in cancer, here, we constructed Gene Co-expression Networks by using TCGA-derived RNA-seq whole-genome samples corresponding to the four breast cancer molecular subtypes, as well as healthy tissue. We quantify the cis-/trans- co-expression imbalance in all phenotypes. Additionally, we measured the association between co-expression and physical distance between genes, and characterized the ratio of intra/inter-cytoband interactions per phenotype. We confirmed loss of trans- co-expression in all molecular subtypes. We also observed that gene cis- co-expression decays abruptly with distance in all tumors in contrast with healthy tissue. We observed co-expressed gene hotspots, that tend to be connected at cytoband regions, and coincide accurately with already known copy number altered regions, such as Chr17q12, or Chr8q24.3 for all subtypes. Our methodology recovered different alterations already reported for specific breast cancer subtypes, showing how co-expression network approaches might help to capture distinct events that modify the cell regulatory program.

RESUMO

Gastric cancer (GC) is a complex and heterogeneous disease. In recent decades, The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) defined GC molecular subtypes. Unfortunately, these systems require high-cost and complex techniques and consequently their impact in the clinic has remained limited. Additionally, most of these studies are based on European, Asian, or North American GC cohorts. Herein, we report a molecular classification of Chilean GC patients into five subtypes, based on immunohistochemical (IHC) and in situ hybridization (ISH) methods. These were Epstein-Barr virus positive (EBV+), mismatch repair-deficient (MMR-D), epithelial to mesenchymal transition (EMT)-like, and accumulated (p53+) or undetected p53 (p53-). Given its lower costs this system has the potential for clinical applicability. Our results confirm relevant molecular alterations previously reported by TCGA and ACRG. We confirm EBV+ and MMR-D patients had the best prognosis and could be candidates for immunotherapy. Conversely, EMT-like displayed the poorest prognosis; our data suggest FGFR2 or KRAS could serve as potential actionable targets for these patients. Finally, we propose a low-cost step-by-step stratification system for GC patients. To the best of our knowledge, this is the first Latin American report on a molecular classification for GC. Pending further validation, this stratification system could be implemented into the routine clinic.

RESUMO

Breast cancer (BC) is a health problem worldwide; there is evidence that inflammatory cytokines are increased in BC. Macrophage migration inhibitory factor (MIF) has multiple effects on immune cells, inflammation and cancer. Besides, in previous studies, contradictory and uncertain results have been presented on the implication of Th17 cytokine profile in BC. The aim of this study was to evaluate the plasma levels of MIF and the Th17 cytokine profile in BC and their association with their molecular subtypes and clinical stage. A total of 150 women with BC of Ella Binational Breast Cancer Study and 60 healthy women (HW) were evaluated in cross-sectional study. The molecular subtypes were identified by immunohistochemistry. The plasma levels of MIF were quantified by ELISA and Th17 cytokine profile by multiplex system. MIF and IL-17 were significantly increased in BC versus HW (11.1 vs. 5.2 ng/mL and 14.8 pg/mL vs. 2.5 pg/mL p < 0.001, respectively). Our analysis showed that both MIF and IL-17A were associated with increased risk of breast cancer (OR 3.85 CI 95% 1.98-7.50 and OR 4.51 95% 1.83-11.15, respectively), higher in aggressive subtypes Luminal B, HER2 and TN. Likewise, we observed positive correlation between MIF and IL-17A (p < 0.001). In addition, IL-17E was lower in BC versus HW (p <0.001). Likewise, we observed a positive correlation between MIF and IL-17A (p < 0.001). In conclusion, both MIF and IL-17A were associated with high risk for breast cancer and aggressive molecular subtypes.

Assuntos