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BACKGROUND: The influence of Helicobacter-pylori (H. pylori) infection and the characteristics of gastric cancer (GC) on tumor-infiltrating lymphocyte (TIL) levels has not been extensively studied. Analysis of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive information. AIM: To determine the rates of deficient mismatch-repair (dMMR), HER2-status and H. pylori infection and their association with TIL levels in GC. METHODS: Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral (IT), stromal (ST) and invasive-border (IB) compartments. The density of CD3, CD8 and CD163 immune cells, and dMMR and HER2-status were determined by immunohistochemistry (IHC). H. pylori infection was evaluated by routine histology and quantitative PCR (qPCR) in a subset of samples. RESULTS: dMMR was found in 34.4%, HER2+ in 5% and H. pylori-positive in 55.7% of samples. High IT-TIL was associated with grade-3 (P = 0.038), while ST-TIL with grade-1 (P < 0.001), intestinal-histology (P < 0.001) and no-recurrence (P = 0.003). dMMR was associated with high TIL levels in the ST (P = 0.019) and IB (P = 0.01) compartments, and ST-CD3 (P = 0.049) and ST-CD8 (P = 0.05) densities. HER2- was associated with high IT-CD8 (P = 0.009). H. pylori-negative was associated with high IT-TIL levels (P = 0.009) when assessed by routine-histology, and with high TIL levels in the 3 compartments (P = 0.002-0.047) and CD8 density in the IT and ST compartments (P = 0.001) when assessed by qPCR. A longer overall survival was associated with low IT-CD163 (P = 0.003) and CD8/CD3 (P = 0.001 in IT and P = 0.002 in ST) and high IT-CD3 (P = 0.021), ST-CD3 (P = 0.003) and CD3/CD163 (P = 0.002). CONCLUSION: TIL levels were related to dMMR and H. pylori-negativity. Low CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.
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Introduction: Breast cancer is a heterogeneous disease, and the distribution of the different subtypes varies by race/ethnic category in the United States and by country. Established breast cancer-associated factors impact subtype-specific risk; however, these included limited or no representation of Latin American diversity. To address this gap in knowledge, we report a description of demographic, reproductive, and lifestyle breast cancer-associated factors by age at diagnosis and disease subtype for The Peruvian Genetics and Genomics of Breast Cancer (PEGEN-BC) study. Methods: The PEGEN-BC study is a hospital-based breast cancer cohort that includes 1943 patients diagnosed at the Instituto Nacional de Enfermedades Neoplásicas in Lima, Peru. Demographic and reproductive information, as well as lifestyle exposures, were collected with a questionnaire. Clinical data, including tumor Hormone Receptor (HR) status and Human Epidermal Growth Factor Receptor 2 (HER2) status, were abstracted from electronic medical records. Differences in proportions and mean values were tested using Chi-squared and one-way ANOVA tests, respectively. Multinomial logistic regression models were used for multivariate association analyses. Results: The distribution of subtypes was 52% HR+HER2-, 19% HR+HER2+, 16% HR-HER2-, and 13% HR-HER2+. Indigenous American (IA) genetic ancestry was higher, and height was lower among individuals with the HR-HER2+ subtype (80% IA vs. 76% overall, p=0.007; 152 cm vs. 153 cm overall, p=0.032, respectively). In multivariate models, IA ancestry was associated with HR-HER2+ subtype (OR=1.38,95%CI=1.06-1.79, p=0.017) and parous women showed increased risk for HR-HER2+ (OR=2.7,95%CI=1.5-4.8, p<0.001) and HR-HER2- tumors (OR=2.4,95%CI=1.5-4.0, p<0.001) compared to nulliparous women. Multiple patient and tumor characteristics differed by age at diagnosis (<50 vs. >=50), including ancestry, region of residence, family history, height, BMI, breastfeeding, parity, and stage at diagnosis (p<0.02 for all variables). Discussion: The characteristics of the PEGEN-BC study participants do not suggest heterogeneity by tumor subtype except for IA genetic ancestry proportion, which has been previously reported. Differences by age at diagnosis were apparent and concordant with what is known about pre- and post-menopausal-specific disease risk factors. Additional studies in Peru should be developed to further understand the main contributors to the specific age of onset and molecular disease subtypes in this population and develop population-appropriate predictive models for prevention.
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OBJECTIVE: To evaluate the relationship between circulating tumor DNA (ctDNA) presence and tumor features including tumor-infiltrating lymphocyte (TIL) levels in Peruvian breast cancer patients. MATERIALS AND METHODS: This was a prospective study conducted at the Instituto Nacional de Enfemedades Neoplasicas, Peru. We evaluated level of TIL and PIK3CA mutations in ctDNA. Clinical characteristics, including outcome data, were collected from the patient file. Survival was calculated from the date of blood sample drawn to the event time. Data collected were analyzed using SPSS software version 25. RESULTS: We analyzed plasma samples from 183 breast cancer patients. most cases were of Luminal-B (44.8%) phenotype and stage II (41.5%), and median stromal TIL was 30%. PIK3CA mutation in ctDNA was detected in 35% cases (most with E545K) and was associated with lower TIL level (p=0.04). PIK3CA in ctDNA tended to be associated with advanced stages (p=0.09) in the whole series and with higher recurrence rates (p=0.053) in the non-metastatic setting. Patients with presence of PIK3CA in ctDNA tended to have shorter survival (p=0.083). CONCLUSION: Presence of PIK3CA mutation in ctDNA was frequently found in our Peruvian breast cancer series, was associated with lower TIL levels and tended to predict poor outcomes.
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DNA Tumoral Circulante , Neoplasias , Linfócitos do Interstício Tumoral/patologia , Peru , Estudos Prospectivos , Classe I de Fosfatidilinositol 3-Quinases/genética , DNA Tumoral Circulante/genética , Mutação , Biomarcadores Tumorais/genética , Neoplasias/patologiaRESUMO
BACKGROUND: Breast cancer incidence in the United States is lower in Hispanic/Latina (H/L) compared with African American/Black or Non-Hispanic White women. An Indigenous American breast cancer-protective germline variant (rs140068132) has been reported near the estrogen receptor 1 gene. This study tests the association of rs140068132 and other polymorphisms in the 6q25 region with subtype-specific breast cancer risk in H/Ls of high Indigenous American ancestry. METHODS: Genotypes were obtained for 5,094 Peruvian women with (1,755) and without (3,337) breast cancer. Associations between genotype and overall and subtype-specific risk for the protective variant were tested using logistic regression models and conditional analyses, including other risk-associated polymorphisms in the region. RESULTS: We replicated the reported association between rs140068132 and breast cancer risk overall [odds ratio (OR), 0.53; 95% confidence interval (CI), 0.47-0.59], as well as the lower odds of developing hormone receptor negative (HR-) versus HR+ disease (OR, 0.77; 95% CI, 0.61-0.97). Models, including HER2, showed further heterogeneity with reduced odds for HR+HER2+ (OR, 0.68; 95% CI, 0.51-0.92), HR-HER2+ (OR, 0.63; 95% CI, 0.44-0.90) and HR-HER2- (OR, 0.77; 95% CI, 0.56-1.05) compared with HR+HER2-. Inclusion of other risk-associated variants did not change these observations. CONCLUSIONS: The rs140068132 polymorphism is associated with decreased risk of breast cancer in Peruvians and is more protective against HR- and HER2+ diseases independently of other breast cancer-associated variants in the 6q25 region. IMPACT: These results could inform functional analyses to understand the mechanism by which rs140068132-G reduces risk of breast cancer development in a subtype-specific manner. They also illustrate the importance of including diverse individuals in genetic studies.
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Neoplasias da Mama , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etnologia , Neoplasias da Mama/genética , Cromossomos Humanos Par 6 , Feminino , Hispânico ou Latino , Humanos , Modelos Logísticos , Peru/epidemiologia , Receptor ErbB-2/genética , Receptores de Estrogênio/genética , Receptores de Progesterona/genéticaRESUMO
OBJECTIVE: To evaluate the frequency distribution of viral infections in Peruvian Breast Cancer (BC) lesions and its association with clinicopathological features. Additionally, a prospective evaluation of p16 and Tumor-infiltrating lymphocytes (TIL) levels were performed for developing a comprehensive analysis. METHODS: Detection of high risk- human papillomavirus (HR- HPV) through qPCR was performed in 447 BC and 79 non-cancer frozen samples. Paired paraffin samples from 238 BC were stained with Human cytomegalovirus (HCMV) and p16 immunohistochemistry. TIL was calculated in 397 BC cases. RESULTS: HCMV was positive in 72.5%. HR- HPV was detected in 2.9% of BC and 1.3% of non-malignant samples. P16+ was found in 28.15% and median TIL percentage was 30. HR- HPV infection was associated with non-ductal histology (p=0.003) and p16+ (p=0.017). Positive P16+ was associated with higher T stage (p=0.022), grade (p=0.009), TIL level (p=0.002), and triple-negative phenotype (p=0.021). CONCLUSION: HCMV is frequent, but HR- HPV infection is unusual in Peruvian BC. P16+ is associated with HR- PVH infection, high TIL and aggressive features.
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Alphapapillomavirus , Neoplasias da Mama , Infecções por Citomegalovirus , Infecções por Papillomavirus , Alphapapillomavirus/genética , Biomarcadores Tumorais/análise , Neoplasias da Mama/complicações , Neoplasias da Mama/epidemiologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/epidemiologia , Feminino , Humanos , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Peru/epidemiologia , Coloração e RotulagemRESUMO
Triple-negative breast cancer (TNBC) is a highly complex, heterogeneous disease and historically has limited treatment options. It has a high probability of disease recurrence and rapid disease progression despite adequate systemic treatment. Immunotherapy has emerged as an important alternative in the management of this malignancy, showing an impact on progression-free survival and overall survival in selected populations. In this review we focused on immunotherapy and its current relevance in the management of TNBC, including various scenarios (metastatic and early -neoadjuvant, adjuvant-), new advances in this subtype and the research of potential predictive biomarkers of response to treatment.
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BACKGROUND: Breast cancer (BC) frequency in males is extremely low and tumor features vary from its female counterpart. Breast cancer clinical and pathological features differ by race in women. Tumor infiltrating lymphocyte (TIL) levels, mismatch repair (MMR) protein loss, androgen receptor (AR) expression, and PIK3CA gene mutations are predictive biomarkers of response to biological therapy in female BC. There is limited information about clinical and pathological features as well as predictive biomarkers in males of non-Caucasian races with BC. AIM: To investigate clinicopathological features and biomarkers of BC tumors in males and their prognostic value in Peruvian population. METHODS: This study looked at a single-institution series of 54 Peruvian males with invasive BC who were diagnosed from Jan 2004 to June 2018. Standard pathological features, TIL levels, MMR proteins, AR immunohistochemistry staining, and PIK3CA gene mutations were prospectively evaluated in cases with available paraffin material. Percentage of AR and estrogen receptor (ER) positive cells was additionally calculated by software after slide scanning. Statistical analyses included association tests, intraclass correlation test and Kaplan Meier overall survival curves. RESULTS: The median age was 63 years and most cases were ER-positive (85.7%), HER2 negative (87.2%), Luminal-A phenotype (60%) and clinical stage II (41.5%) among our male breast tumors. Median TIL was 10% and higher levels tended to be associated with Luminal-B phenotype and higher grade. AR-positive was found in 85.3% and was correlated with ER (intraclass index of 0.835, P < 0.001). Loss of MMR proteins was found in 15.4% and PIK3CA mutation (H1047R) in 14.3% (belonged to the Luminal-A phenotype). Loss of MMR proteins was associated with AR-negative (P = 0.018) but not with ER (P = 0.43) or TIL (P = 0.84). Early stages (P < 0.001) and lower grade (P = 0.006) were associated with longer overall survival. ER status, phenotype, AR status, TIL level, MMR protein loss nor PIK3CA mutation was not associated with survival (P > 0.05). CONCLUSION: Male BC is usually ER and AR positive, and Luminal-A. MMR loss and PIK3CA mutations are infrequent. Stage and grade predicted overall survival in our South American country population.
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RESUMEN Objetivo: El desarrollo de cuadros severos y la muerte por COVID-19 son más frecuentes en poblaciones con comorbilidades. Algunos estudios describen mayor frecuencia de cuadros severos en pacientes con cáncer. Esta revisión sistemática tiene por objetivo describir el riesgo de infección y de presentar un cuadro severo por COVID-19 en pacientes oncológicos. Materiales y métodos: Se realizó una revisión sistemática mediante una búsqueda de la literatura en PubMed y Scopus hasta mayo de 2020. Se amplió la inclusión de estudios con una búsqueda secundaria. Resultados: La búsqueda inicial identificó 2192 registros, de los que se incluyeron 17 publicaciones con al menos 10 pacientes oncológicos infectados. Además, se incluyeron cinco artículos de la búsqueda adicional de las referencias citadas en los 17 artículos. Diez publicaciones provenían de autores chinos. El análisis de la información indicó que la infección es más frecuente en pacientes con cáncer, y las frecuentes visitas terapéuticas al establecimiento de salud serían las causantes. La COVID-19 severa es más frecuente en pacientes con cáncer, y factores como la edad avanzada, comorbilidades asociadas, estadio avanzado y marcadores séricos de inflamación incrementan la severidad del cuadro. Estudios iniciales realizados en China encuentran que el uso de tratamiento antineoplásico sistémico podría también ser un factor predisponente. Conclusiones: El riesgo de infección y de desarrollar cuadro severo por COVID-19 es mayor en la población oncológica.
ABSTRACT Objective: Development of severe disease and death from COVID-19 is more frequent in patients with comorbidities. Some studies report an increased frequency of severe COVID-19 in cancer patients. This review aims to describe the risk of infection and developing severe COVID-19 in cancer patients. Materials and methods: A systematic review was carried out through an exhaustive search of literature in PubMed and Scopus until May 2020. A secondary search was performed to include more studies. Results: The initial search identified 2,192 records, which included 17 publications with at least 10 infected cancer patients. Also, 5 articles were added from the additional search of the references cited by those 17 publications. Ten publications were from Chinese authors. Data analysis showed that COVID-19 infection is more frequent in cancer patients, and frequent therapeutic visits to the healthcare facility may be the cause. The presence of neoplasia predisposed patients to develop severe disease. Advanced age, associated comorbidities, advanced malignancy, and the presence of serum inflammatory markers increased the risk of developing severe disease. Initial studies indicate that the use of systemic treatment may also be a predisposing factor. Conclusions: The risk of becoming infected by COVID-19 and developing severe disease is higher in the oncological population.
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Publicações , COVID-19 , Neoplasias , Pacientes , Comorbidade , Fatores de Risco , Coronavirus , LiteraturaRESUMO
RESUMEN Introducción. En Perú, el cáncer de mama representa el tipo de cáncer más frecuente en mujeres y el sexto tipo de cáncer más letal en la población general. La sobreexpresión del receptor del factor de crecimiento epidérmico (HER2+) ocurre en 20% a 30% de los cánceres de mama, y se asocia con tumores más agresivos, con mayor recurrencia y mayor mortalidad. Objetivo. Elaborar un conjunto de recomendaciones basadas en evidencias para el diagnóstico y tratamiento del cáncer de mama HER2+, con la finalidad de contribuir a reducir la mortalidad, progresión de la enfermedad y mejorar la calidad de vida. Métodos. Se conformó un panel de especialistas clínicos y metodólogos, quienes identificaron preguntas clínicas relevantes sobre el diagnóstico y tratamiento del cáncer de mama HER2+. Se desarrolló una búsqueda sistemática de GPC en Medline (PubMed), y en organismos elaboradores y recopiladores. Para la formulación de recomendaciones, el panel de especialistas discutió la evidencia y elementos del contexto de implementación de la recomendación, siguiendo la metodología propuesta por el Ministerio de Salud del Perú. Resultados. Se priorizó nueve preguntas clínicas. Se formuló un total de 25 recomendaciones clínicas. Conclusiones. Se elaboró una GPC basada en evidencias, a través de un proceso sistemático, riguroso y transparente desarrollado por un equipo multidisciplinario.
ABSTRACT Introduction. In Peru, breast cancer represents the most common type of cancer in women and the sixth most lethal type of cancer in the general population. Overexpression of the epidermal growth factor receptor (HER2 +) occurs in 20% to 30% of breast cancers, and is associated with more aggressive tumors, with greater recurrence and greater mortality. Objective. Prepare a set of evidence-based recommendations for the diagnosis and treatment of HER2 + breast cancer, in order to help reduce mortality, disease progression and improve quality of life. Methods. A panel of clinical specialists and methodologists was formed, who identified relevant clinical questions about the diagnosis and treatment of HER2 + breast cancer. A systematic search for CPGs was carried out in Medline (PubMed), and in developing and compiling agencies. For the formulation of recommendations, the panel of specialists discussed the evidence and elements of the context of implementation of the recommendation, following the methodology proposed by the Ministry of Health of Peru. Results. Nine clinical questions were prioritized. A total of 25 clinical recommendations were made. Conclusions. An evidence-based CPG was developed through a systematic, rigorous and transparent process developed by a multidisciplinary team.
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Women of Latin American origin in the United States are more likely to be diagnosed with advanced breast cancer and have a higher risk of mortality than non-Hispanic White women. Studies in U.S. Latinas and Latin American women have reported a high incidence of HER2 positive (+) tumors; however, the factors contributing to this observation are unknown. Genome-wide genotype data for 1,312 patients from the Peruvian Genetics and Genomics of Breast Cancer Study (PEGEN-BC) were used to estimate genetic ancestry. We tested the association between HER2 status and genetic ancestry using logistic and multinomial logistic regression models. Findings were replicated in 616 samples from Mexico and Colombia. Average Indigenous American (IA) ancestry differed by subtype. In multivariate models, the odds of having an HER2+ tumor increased by a factor of 1.20 with every 10% increase in IA ancestry proportion (95% CI, 1.07-1.35; P = 0.001). The association between HER2 status and IA ancestry was independently replicated in samples from Mexico and Colombia. Results suggest that the high prevalence of HER2+ tumors in Latinas could be due in part to the presence of population-specific genetic variant(s) affecting HER2 expression in breast cancer. SIGNIFICANCE: The positive association between Indigenous American genetic ancestry and HER2+ breast cancer suggests that the high incidence of HER2+ subtypes in Latinas might be due to population and subtype-specific genetic risk variants.
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Neoplasias da Mama/química , Neoplasias da Mama/etnologia , Hispânico ou Latino/genética , Receptor ErbB-2/análise , Adulto , Idoso , Povo Asiático/etnologia , Povo Asiático/estatística & dados numéricos , População Negra/etnologia , População Negra/estatística & dados numéricos , Neoplasias da Mama/genética , Colômbia/etnologia , Feminino , Humanos , Indígenas Norte-Americanos , Indígenas Sul-Americanos , América Latina/etnologia , Modelos Lineares , Modelos Logísticos , México/etnologia , Pessoa de Meia-Idade , Peru/etnologia , Receptor ErbB-2/genética , Receptores de Estrogênio/sangue , Receptores de Progesterona/sangue , Estados Unidos , População Branca/etnologia , População Branca/estatística & dados numéricos , Adulto JovemRESUMO
OBJECTIVE: Development of severe disease and death from COVID-19 is more frequent in patients with comorbidities. Some studies report an increased frequency of severe COVID-19 in cancer patients. This review aims to describe the risk of infection and developing severe COVID-19 in cancer patients. MATERIALS AND METHODS: A systematic review was carried out through an exhaustive search of literature in PubMed and Scopus until May 2020. A secondary search was performed to include more studies. RESULTS: The initial search identified 2,192 records, which included 17 publications with at least 10 infected cancer patients. Also, 5 articles were added from the additional search of the references cited by those 17 publications. Ten publications were from Chinese authors. Data analysis showed that COVID-19 infection is more frequent in cancer patients, and frequent therapeutic visits to the healthcare facility may be the cause. The presence of neoplasia predisposed patients to develop severe disease. Advanced age, associated comorbidities, advanced malignancy, and the presence of serum inflammatory markers increased the risk of developing severe disease. Initial studies indicate that the use of systemic treatment may also be a predisposing factor. CONCLUSIONS: The risk of becoming infected by COVID-19 and developing severe disease is higher in the oncological population.
OBJETIVO: El desarrollo de cuadros severos y la muerte por COVID-19 son más frecuentes en poblaciones con comorbilidades. Algunos estudios describen mayor frecuencia de cuadros severos en pacientes con cáncer. Esta revisión sistemática tiene por objetivo describir el riesgo de infección y de presentar un cuadro severo por COVID-19 en pacientes oncológicos. MATERIALES Y MÉTODOS: Se realizó una revisión sistemática mediante una búsqueda de la literatura en PubMed y Scopus hasta mayo de 2020. Se amplió la inclusión de estudios con una búsqueda secundaria. RESULTADOS: La búsqueda inicial identificó 2192 registros, de los que se incluyeron 17 publicaciones con al menos 10 pacientes oncológicos infectados. Además, se incluyeron cinco artículos de la búsqueda adicional de las referencias citadas en los 17 artículos. Diez publicaciones provenían de autores chinos. El análisis de la información indicó que la infección es más frecuente en pacientes con cáncer, y las frecuentes visitas terapéuticas al establecimiento de salud serían las causantes. La COVID-19 severa es más frecuente en pacientes con cáncer, y factores como la edad avanzada, comorbilidades asociadas, estadio avanzado y marcadores séricos de inflamación incrementan la severidad del cuadro. Estudios iniciales realizados en China encuentran que el uso de tratamiento antineoplásico sistémico podría también ser un factor predisponente. CONCLUSIONES: El riesgo de infección y de desarrollar cuadro severo por COVID-19 es mayor en la población oncológica.
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COVID-19/epidemiologia , Mediadores da Inflamação/sangue , Neoplasias/complicações , Fatores Etários , COVID-19/mortalidade , COVID-19/fisiopatologia , Comorbidade , Humanos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: To evaluate the correlation between the presence of H. pylori in paired samples of tap water and gastric cancer (GC) lesion in Lima city (Peru). MATERIAL AND METHODS: Gastric tissue and tap-water samples were prospectively collected from 82 Gastric Cancer who lived in Lima. HspA and ureA genes were evaluated by qPCR in the samples. Results: The median age of patients with GC was 63 years, 52.4% were men and stage-II in 36.6%. A home-living time> 10 years was reported in 84.1% of patients. Boiling water treatment was indicated in 85.4% of cases. H. pylori was detected in 69.5% of gastric tissues and in 12.2% of analyzed tap-water. There was no differences in gastric infection rates among those with or without water contamination (70% vs. 69.4%, p=0.971). Conclusion & Impact: H. pylori was found in tap-water samples, however, detection rates were lower than in gastric cancer samples. Other sources of infection transmission should be investigated.
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Adenocarcinoma/epidemiologia , Infecções por Helicobacter/complicações , Helicobacter pylori/isolamento & purificação , Neoplasias Gástricas/epidemiologia , Microbiologia da Água/normas , Abastecimento de Água/normas , Adenocarcinoma/microbiologia , Adenocarcinoma/patologia , Feminino , Seguimentos , Infecções por Helicobacter/microbiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Peru/epidemiologia , Prognóstico , Estudos Prospectivos , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologiaRESUMO
Aim: To correlate levels of tumor-infiltrating lymphocytes (TIL) evaluated using the International Immuno-Oncology Biomarker Working Group methodology, and both density of tumor-infiltrating immune cell and clinicopathological features in different malignancies. Methods: 209 pathological samples from gastric cancer, cervical cancer (CC), non-small-lung cancer, cutaneous melanoma (CM) and glioblastoma were tested for TIL in hematoxylin eosin, and density of CD3+, CD4+, CD8+, CD20+, CD68+ and CD163+ cells by digital analysis. Results: TIL levels were higher in invasive margin compartments (IMC). TIL in IMC, intratumoral and stromal compartments predicted survival. CC and gastric cancer had higher TIL in intratumoral; CC and CM had higher TIL in stromal compartment and IMC. CM had the highest density of lymphocyte and macrophage populations. CD20 density was associated with survival in the whole series. Conclusion: Standardized evaluation of TIL levels may provide valuable prognostic information in a spectrum of different malignancies.
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Linfócitos do Interstício Tumoral/citologia , Neoplasias/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Contagem de Leucócitos , Macrófagos/citologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
PURPOSE: Helicobacter pylori (HP) and Epstein Barr virus (EBV) infections induce chronic gastritis (CG) and are accepted carcinogenics of gastric cancer (GC). Our objective for this study was to determine the prevalence of these agents and clinicopathological features of GC and CG associated with the infection. PATIENTS AND METHODS: A single-center cohort of 375 Peruvian patients with GC and 165 control subjects with CG were analyzed. Evaluation of HP and EBV genes was performed through quantitative polymerase chain reaction. RESULTS: Prevalence of HP was 62.9% in the whole population and 60.8% in the GC subset. The cagA gene was detected in 79.9%; vacAs1 and vacAm1 alleles in 41.6% and 60.7%, respectively; and concurrent expression of vacAs1 and vacAm1 in 30.4% of infected patients in the whole series. The prevalence of EBV was 14.1% in the whole population and was higher in GC (P < .001). Coinfection of HP and EBV was found in 7.8% and was also higher in GC in univariate (P < .001) and multivariate (P = .011) analyses. Infection rates of HP and EBV were not associated with a geographic location in the whole series. Few clinicopathological features have been associated with infectious status. CONCLUSION: Prevalence of HP infection and virulent strains are high in the Peruvian population. Infection by EBV was more frequent in patients with GC.
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Infecções por Vírus Epstein-Barr/epidemiologia , Gastrite/complicações , Helicobacter pylori/patogenicidade , Neoplasias Gástricas/complicações , Doença Crônica , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Peru , PrevalênciaAssuntos
Antígenos CD/análise , Antígenos CD8/análise , Moléculas de Adesão Celular Neuronais/análise , Proteínas Fetais/análise , Linfócitos do Interstício Tumoral/imunologia , Receptores Androgênicos/análise , Neoplasias de Mama Triplo Negativas , Biomarcadores Tumorais/análise , Adesão Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Prognóstico , Ribonucleoproteínas Nucleolares Pequenas/análise , Análise de Sobrevida , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
AIM: Evaluation of features related to infiltrating immune cell level in glioblastoma. METHODS: Tumor-infiltrating lymphocytes (TILs) through H&E staining, and TILs (CD3, CD4, CD8 and CD20) and macrophage (CD68 and CD163) levels through immunohistochemistry were evaluated through digital analysis. RESULTS: CD68 (9.1%), CD163 (2.2%), CD3 (1.6%) and CD8 (1.6%) had the highest density. Higher CD4+ was associated with unmethylated MGMT (p = 0.016). Higher CD8+ was associated with larger tumoral size (p = 0.027). Higher CD163+ was associated with higher age (p = 0.044) and recursive partitioning analysis = 4. Women (p < 0.05), total resection (p < 0.05), MGMT-methylation (p < 0.001), radiotherapy (p < 0.001), chemotherapy (p < 0.001) and lower CD4+ (p < 0.05) were associated with longer overall survival. CONCLUSION: Macrophages are more frequent than TILs. Some subsets are associated with clinical features.
Assuntos
Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Linfócitos do Interstício Tumoral/patologia , Macrófagos/patologia , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/terapia , Criança , Estudos de Coortes , Metilação de DNA , Metilases de Modificação do DNA/genética , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/genética , Enzimas Reparadoras do DNA/metabolismo , Feminino , Glioblastoma/genética , Glioblastoma/imunologia , Glioblastoma/terapia , Humanos , Linfócitos do Interstício Tumoral/imunologia , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Adulto JovemRESUMO
Latina women in the U.S. have relatively low breast cancer incidence compared to Non-Latina White (NLW) or African American women but are more likely to be diagnosed with the more aggressive "triple negative" breast cancer (TNBC). Latinos in the U.S. are a heterogeneous group originating from different countries with different cultural and ancestral backgrounds. Little is known about the distribution of tumor subtypes in Latin American regions. Clinical records of 303 female Peruvian patients, from the Peruvian National Cancer Institute, were analyzed. Participants were diagnosed with invasive breast cancer between 2010 and 2015 and were identified as residing in either the Selva or Sierra region. We used Fisher's exact test for proportions and multivariable Cox Proportional Hazards Models to compare overall survival between regions. Women from the Selva region were more likely to be diagnosed with TNBC than women from the Sierra region (31% vs. 14%, p = 0.01). In the unadjusted Cox model, the hazard of mortality was 1.7 times higher in women from the Selva than the Sierra (p = 0.025); this survival difference appeared to be largely explained by differences in the prevalence of TNBC. Our results suggest that the distribution of breast cancer subtypes differs between highly Indigenous American women from two regions of Peru. Disentangling the factors that contribute to this difference will add valuable information to better target prevention and treatment efforts in Peru and improve our understanding of TNBC among all women. This study demonstrates the need for larger datasets of Latin American patients to address differences between Latino subpopulations and optimize targeted prevention and treatment.
Assuntos
Neoplasias de Mama Triplo Negativas/classificação , Neoplasias de Mama Triplo Negativas/mortalidade , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Peru/epidemiologia , Taxa de Sobrevida , Neoplasias de Mama Triplo Negativas/terapiaRESUMO
Tuberculosis (TB) is a major public health problem that, due to the clinical variability of its presentation, can be confused with cancer. The aim of this study was to identify the clinical-radiological characteristics and to describe the methodology that allowed to achieve a TB diagnosis in patients referred to the National Institute of Neoplastic Diseases (INEN) with a presumed diagnosis of cancer between 2014 and 2016. The study included 170 patients (52.4% men) with an average age of 41.1 years; 18% presented a history of contact with TB, and 5.9% had had the disease previously. The TB was pulmonary in 22.4% and extrapulmonary in 77.7% of patients. The most frequent symptoms were respiratory, tumor, weight loss, and neurological. The cancer diagnoses most frequently discarded were lymphoma, lung cancer, and brain cancer. The lesions that suggested a neoplasm indicated an advanced clinical stage in 63.5%. Therefore, it follows that the symptoms and images associated with TB can be confused with malignant neoplasms.
La tuberculosis (TB) es un importante problema de salud pública que debido a la variabilidad clínica de su presentación, puede confundirse con una malignidad. El objetivo del estudio fue identificar las características clínico radiológicas y describir la metodología que permitió llegar al diagnóstico de TB en pacientes derivados con presunción diagnóstica de cáncer al Instituto Nacional de Enfermedades Neoplásicas (INEN) entre 2014 y 2016. Se incluyeron 170 pacientes (52,4 % hombres) con edad promedio de 41,1 años, 18 % presentaron antecedentes de contacto con TB y un 5,9 % tuvo previamente la enfermedad. La TB fue pulmonar en 22,4 % y extrapulmonar en 77,7 % de los pacientes. Los síntomas más frecuentes fueron respiratorios, tumoración, pérdida de peso y neurológicos. Los diagnósticos oncológicos descartados con mayor frecuencia fueron linfoma, cáncer pulmonar y cerebral. Las lesiones que sugerían una neoplasia indicaron un estadio clínico avanzado en el 63,5 %. Se concluye que los síntomas e imágenes asociados a TB pueden confundirse con neoplasias malignas.
Assuntos
Neoplasias/diagnóstico , Tuberculose/diagnóstico , Academias e Institutos , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Peru , Encaminhamento e Consulta , Estudos RetrospectivosRESUMO
AIM: To investigate the survival impact of clinicopathological factors, including pathological complete response (pCR) and tumor-infiltrating lymphocytes (sTIL) levels according to subtypes, in breast cancer (BC) patients who received neo-adjuvant chemotherapy (NAC). METHODS: We evaluated 435 BC patients who presented and received NAC at the Instituto Nacional de Enfermedades Neoplasicas from 2003 to 2014. sTIL was analyzed as the proportion of tumor stroma occupied by lymphocytes, and was prospectively evaluated on hematoxylin and eosin-stained sections of the preNAC core biopsy. pCR was considered in the absence of infiltrating cancer cells in primary tumor and axillary lymph nodes. Analysis of statistical association between clinical pathological features, sTIL, pCR and survival were carried out using SPSSvs19. RESULTS: Median age was 49 years (range 24-84 years) and the most frequent clinical stage was IIIB (58.3%). Luminal A, Luminal B, HER2-enriched and (triple-negative) TN phenotype was found in 24.6%, 37.9%, 17.7% and 19.8%, respectively. pCR was observed in 11% and median percentage of sTIL was 40% (2%-95%) in the whole population. pCR was associated to Ct1-2 (P = 0.045) and to high sTIL (P = 0.029) in the whole population. There was a slight trend towards significance for sTIL (P = 0.054) in Luminal A. sTIL was associated with grade III (P < 0.001), no-Luminal A subtype (P < 0.001), RE-negative (P < 0.001), PgR-negative (P < 0.001), HER2-positive (P = 0.002) and pCR (P = 0.029) in the whole population. Longer disease-free survival was associated with grade I-II (P = 0.006), cN0 (P < 0.001), clinical stage II (P = 0.004), ER-positive (P < 0.001), PgR-positive (P < 0.001), luminal A (P < 0.001) and pCR (P = 0.002). Longer disease-free survival was associated with grade I-II in Luminal A (P < 0.001), N0-1 in Luminal A (P = 0.045) and TNBC (P = 0.01), clinical stage II in Luminal A (P = 0.003) and TNBC (P = 0.038), and pCR in TNBC (P < 0.001). Longer overall survival was associated with grade I-II (P < 0.001), ER-positive (P < 0.001), PgR-positive (P < 0.001), Luminal A (P < 0.001), cN0 (P = 0.002) and pCR (P = 0.002) in the whole population. Overall survival was associated with clinical stage II (P = 0.017) in Luminal A, older age (P = 0.042) in Luminal B, and pCR in TNBC (P = 0.005). CONCLUSION: Predictive and prognostic values of clinicopathological features, like pCR and sTIL, differ depending on the evaluated molecular subtype.
RESUMO
AIM: To evaluate the prognostic value of tumor-infiltrating lymphocytes (TILs) and Ki67 in brain metastasis lesions, and the effect of adding them to variables of graded prognostic assessment score. PATIENTS & METHODS: Clinicopathological information from 111 medical charts of brain metastasis patients was obtained, and TIL distribution (n = 84), Ki67 index (n = 79) and CD3 TIL (n = 64) were prospectively evaluated. RESULTS: Most frequent TIL pattern was perivascular (67.8%), and median Ki67 and CD3 TIL percents were 30 and 4.8%, respectively. Ki67 ≥15 was associated with shorter survival (p = 0.018) but CD3 TIL was not (p = 0.870). The highest graded prognostic assessment score was not associated with survival (p = 0.648), however, those with low Ki67 and high score was associated with better outcome (p = 0.007). CONCLUSION: High Ki67 index in brain metastasis carries a worse prognosis.