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PURPOSE: To investigate the application value of support vector machine (SVM) model based on diffusion-weighted imaging (DWI), dynamic contrast-enhanced (DCE) and amide proton transfer- weighted (APTW) imaging in predicting isocitrate dehydrogenase 1(IDH-1) mutation and Ki-67 expression in glioma. METHODS: The DWI, DCE and APTW images of 309 patients with glioma confirmed by pathology were retrospectively analyzed and divided into the IDH-1 group (IDH-1(+) group and IDH-1(-) group) and Ki-67 group (low expression group (Ki-67 ≤ 10%) and high expression group (Ki-67 > 10%)). All cases were divided into the training set, and validation set according to the ratio of 7:3. The training set was used to select features and establish machine learning models. The SVM model was established with the data after feature selection. Four single sequence models and one combined model were established in IDH-1 group and Ki-67 group. The receiver operator characteristic (ROC) curve was used to evaluate the diagnostic performance of the model. Validation set data was used for further validation. RESULTS: Both in the IDH-1 group and Ki-67 group, the combined model had better predictive efficiency than single sequence model, although the single sequence model had a better predictive efficiency. In the Ki-67 group, the combined model was built from six selected radiomics features, and the AUC were 0.965 and 0.931 in the training and validation sets, respectively. In the IDH-1 group, the combined model was built from four selected radiomics features, and the AUC were 0.997 and 0.967 in the training and validation sets, respectively. CONCLUSION: The radiomics model established by DWI, DCE and APTW images could be used to detect IDH-1 mutation and Ki-67 expression in glioma patients before surgery. The prediction performance of the radiomics model based on the combination sequence was better than that of the single sequence model.
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Neoplasias Encefálicas , Glioma , Isocitrato Deshidrogenasa , Antígeno Ki-67 , Mutación , Máquina de Vectores de Soporte , Humanos , Isocitrato Deshidrogenasa/genética , Glioma/diagnóstico por imagen , Glioma/genética , Glioma/metabolismo , Antígeno Ki-67/metabolismo , Antígeno Ki-67/genética , Persona de Mediana Edad , Femenino , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Masculino , Estudios Retrospectivos , Adulto , Anciano , Imagen de Difusión por Resonancia Magnética/métodos , Imagen Multimodal , Adulto Joven , Imagen por Resonancia Magnética/métodos , Curva ROC , Medios de ContrasteRESUMEN
Apocrine sweat gland adenocarcinoma (ASGAC) is a rare skin carcinoma in cats. In some cases, this tumor occurs in anatomical sites of challenging wide surgical resection, which increases the need for adjuvant therapies for residual disease. These include radiotherapy or electrochemotherapy (ECT), local treatments for invasive tumors in companion animals often associated with surgery. However, the current literature for ASGAC treatment is limited and there are no reports of ECT as an adjuvant therapy. In this case report, we account for the case of an 11-year-old cat with a history of a non-ulcerated recurrent ASGAC, measuring 1.3 × 1.0 cm, located by the rostral mandibular region. Surgical resection included the angularis oris axial flap for facial reconstruction associated with electroporation of the surgical bed and, post-operatively, in the surgical scar. Histopathological results confirmed the presence of a recurrent ASGAC. Immunostaining revealed cyclooxygenase 2 (COX-2) expression with a score of 6, 50 % positivity in Ki-67, and positive for pan-cytokeratin (PCK AE-1/ AE-3). A selective COX-2 inhibitor was initiated along with systemic chemotherapy with chlorambucil. The local approach including surgery and ECT was chosen due to the unfavorable anatomical site for extensive resection and the unavailability of radiotherapy. Subsequently, carboplatin chemotherapy was required due to metastasis in the mandibular lymph node. This case report supports the effectiveness of a multimodal treatment including surgery, ECT, and chemotherapy in a cat with recurrent ASGAC.
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Statins, inhibitors of HMG-CoA reductase, have been shown to have potential anti-carcinogenic effects through the inhibition of the mevalonate pathway and their impact on Ras and RhoGTAases. Prior studies have demonstrated a reduction in breast tumor proliferation, as well as increased apoptosis, among women with early-stage breast cancer who received statins between the time of diagnosis and the time of surgery. The aim of this study was to evaluate the impact of short-term oral high-potency statin therapy on the expression of markers of breast tumor proliferation, apoptosis, and cell cycle arrest in a window-of-opportunity trial. This single-arm study enrolled 24 women with stage 0-II invasive breast cancer who were administered daily simvastatin (20 mg) for 2-4 weeks between diagnosis and surgical resection. Pre- and post-treatment tumor samples were analyzed for fold changes in Ki-67, cyclin D1, p27, and cleaved caspase-3 (CC3) expression. Out of 24 enrolled participants, 18 received statin treatment and 17 were evaluable for changes in marker expression. There was no significant change in Ki-67 expression (fold change = 1.4, p = 0.597). There were, however, significant increases in the expression of cyclin D1 (fold change = 2.8, p = 0.0003), p27 cytoplasmic (fold change = 3.2, p = 0.025), and CC3 (fold change = 2.1, p = 0.016). Statin treatment was well tolerated, with two reported grade-1 adverse events. These results align with previous window-of-opportunity studies suggesting a pro-apoptotic role of statins in breast cancer. The increased expression of markers of cell cycle arrest and apoptosis seen in this window-of-opportunity study supports further investigation into the anti-cancer properties of statins in larger-scale clinical trials.
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Apoptosis , Biomarcadores de Tumor , Neoplasias de la Mama , Proliferación Celular , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Apoptosis/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Persona de Mediana Edad , Proliferación Celular/efectos de los fármacos , Biomarcadores de Tumor/metabolismo , Anciano , Adulto , Estadificación de Neoplasias , Simvastatina/farmacología , Simvastatina/uso terapéutico , Antígeno Ki-67/metabolismo , Ciclina D1/metabolismo , Caspasa 3/metabolismoRESUMEN
Background: Triple-negative breast cancer (TNBC) displays high heterogeneity. The majority of TNBC cases are characterized by high Ki-67 expression. TNBC with low Ki-67 expression accounts for only a small fraction of cases and has been relatively less studied. Methods: This study analyzed a large single-center multiomics TNBC data set, combined with a single-cell data set. The clinical, genomic, and metabolic characteristics of patients with low Ki-67 TNBC were analyzed. Results: The clinical and pathological characteristics were analyzed in 2217 TNBC patients. Low Ki-67 TNBC was associated with a higher patient age at diagnosis, a lower proportion of invasive ductal carcinoma, increased alterations in the PI3K-AKT-mTOR pathway, upregulated lipid metabolism pathways, and enhanced infiltration of M2 macrophages. High Ki-67 TNBC exhibited a higher prevalence of TP53 gene mutations, elevated nucleotide metabolism, and increased infiltration of M1 macrophages. Conclusions: We identified specific genomic and metabolic characteristics unique to low Ki-67 TNBC, which have implications for the development of precision therapies and patient stratification strategies.
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This study examined to evaluate the predictive value of a nomogram with Ki-67 in overall and disease-free survival in glioma patients, a total of 76 patients diagnosed with glioma by pathology in Tengzhou Central People's Hospital were enrolled. The baseline data and follow ups were retrospectively collected from medical records. The associations between Ki-67 and survival status were examined using log-rank test, univariate and multivariate Cox proportional hazard regression models. Calibrations were performed to validate the established nomograms. Ki-67 negative group showed of a longer OS survival time and a longer PFS survival time with log-rank test (x2 = 16.101, P < 0.001 and x2 = 16.961, P < 0.001). Age older than 50 years (HR = 2.074, 95% CI 1.097-3.923), abnormal treatment (HR = 2.932, 95% CI 1.343-6.403) and Ki-67 positive (HR = 2.722, 95% CI 1.097-6.755) were the independent predictive factors of death. High grade pathology (HR = 2.453, 95% CI 1.010-5.956) and Ki-67 positive (HR = 2.200, 95% CI 1.043-4.639) were the independent predictive factors of recurrence. The C-index for the nomogram of OS and PFS were 0.745 and 0.723, respectively. The calibration results showed that the nomogram could predict the overall and disease-free 1-year survival of glioma patients. In conclusion, the nomograms with Ki-67 as independent risk factor for OS and PFS could provide clinical consultation in the treatment and follow-up of malignant glioma.
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Neoplasias Encefálicas , Glioma , Antígeno Ki-67 , Recurrencia Local de Neoplasia , Nomogramas , Humanos , Glioma/mortalidad , Glioma/cirugía , Glioma/metabolismo , Glioma/patología , Antígeno Ki-67/metabolismo , Femenino , Masculino , Persona de Mediana Edad , Adulto , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Estudios Retrospectivos , Anciano , Pronóstico , Supervivencia sin Enfermedad , Modelos de Riesgos ProporcionalesRESUMEN
BACKGROUND: Papillary thyroid carcinoma (PTC) occasionally invades the trachea and requires airway resection. Tracheal excision site recurrence (ESR) is a serious problem. We investigated predictors of ESR in patients with PTC who underwent airway resection for locally curative surgery. METHODS: We enrolled 149 patients with PTC who underwent airway resection (median age at the initial surgery: 67 years), including partial-thickness resection (n = 73) or full-thickness resection (n = 76), for grossly curative surgery. The median postoperative follow-up period was 93 months. RESULTS: To date, 11 patients (6.7%) underwent ESR: 6 underwent full-thickness resection and 5 underwent partial-thickness resection. The time to ESR ranged from 14 to 113 months (median: 57 months) after the initial surgery. None of the 11 ESR patients underwent adjuvant external beam radiotherapy (EBRT) and none of the 4 airway resection patients who underwent EBRT developed ESR. The 5- and 10-year ESR rates were 4.3% and 11.3%, respectively. In the multivariate analysis (forward-backward stepwise selection method), a Ki-67 labeling index (LI) ≥5% (p = 0.048) and the thyroglobulin doubling rate (Tg-DR) >0.33/year (p = 0.009) (for Tg-antibody negative cases) were independent predictors of ESR. Nine of the 11 patients underwent ESR resection and only one developed a second recurrence. CONCLUSIONS: A high Ki-67 LI was a static predictor, and high Tg-DR was a dynamic predictor, of ESR in patients with PTC following airway resection. In such patients, careful postoperative monitoring for ESR is necessary and adjuvant therapies, such as EBRT, may be considered.
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To formulate a predictive model for assessing Ki-67 expression in breast cancer by integrating pre-treatment ultrasound features with non-morphological magnetic resonance imaging (MRI) parameters, encompassing functional and hemodynamic indicators. A retrospective study was conducted on 167 patients. All patients underwent a breast mass biopsy for histopathological and Ki-67 analysis prior to neoadjuvant chemotherapy (NAC) treatment. Additionally, all patients underwent ultrasonography and MRI examinations prior to the biopsy. The recorded variables were Ki-67, apparent diffusion coefficient (ADC) values, Max Slope, time to peak (TTP), signal enhancement ratio (SER), early enhancement rate (EER), time-signal intensity curve (TIC), tumor maximum diameter, tumor margins and boundaries, aspect ratio, microcalcification, color Doppler flow imaging grading, resistance index (RI), and axillary lymph node metastasis. Statistical analysis was performed using the R software package. Normally distributed continuous data are presented as mean ± standard deviation (SD), skewed continuous data as median, and categorical variables as frequency or percentage. The dataset was randomly divided into a modeling group and a validation group following a 7:3 ratio, employing a predetermined random seed. The selection of variables was conducted using the random forest algorithm. Specifically, in the initial analysis, we trained a random forest model using all available variables. By evaluating the Gini importance scores of each variable, we identified those that contributed the most to predicting Ki-67 expression. The predictive model for Ki-67 expression was constructed using selected variables: Maximum Diameter, ADC value, SER value, Max Slope value, TTP value, and EER value. Within the validation group, the evaluation metrics demonstrated an Area under the curve of 0.961 with a 95% confidence interval ranging from 0.865 to 0.995. The model achieved a kappa score of 1.00, precision of 0.949, recall of 1, an F1 score of 0.974, sensitivity of 100%, specificity of 85.71%, a positive predictive value of 94.87%, and a negative predictive value of 100%. The combination of non-morphological MRI parameters and pre-treatment ultrasound features in a breast cancer prediction model powered by RF machine learning demonstrated favorable clinical outcomes and improved diagnostic performance.
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RATIONALE AND OBJECTIVES: Current radiomics research primarily focuses on intratumoral regions and fixed peritumoral areas, lacking optimization for accurate Ki-67 prediction. This study aimed to develop machine learning (ML) models to analyze radiomic features from Automated Breast Volume Scanning (ABVS) images of different peritumoral region sizes to identify the optimal size for accurate preoperative Ki-67 prediction. MATERIALS AND METHODS: A total of 668 breast cancer patients were enrolled and divided into training (486) and testing (182) cohorts. In the training cohort, ML models were developed for intratumoral and peritumoral regions (2, 4, 6, 8, and 10 mm). Relevant Ki-67 features for each ROI were identified, and different models were compared to determine the optimal one. These models were validated using a testing cohort to find the most accurate peritumoral region for Ki-67 prediction. SHAP (Shapley Additive Explanations) analysis was performed to identify key radiomic features from the optimal model. RESULTS: The Extreme Gradient Boosting (XGBoost) model for the intratumoral region combined with the 6 mm peritumoral region achieved the highest predictive accuracy, with an AUC of 0.957 in the training cohort and 0.920 in the testing cohort. Calibration curves confirmed reliability, and decision curve analysis demonstrated the highest net benefit. SHAP indicated that 6 mm peritumoral radiomic features are more significant than intratumoral features. CONCLUSION: The XGBoost model using ABVS-derived radiomic features from both the intratumoral and 6 mm peritumoral regions provides the most accurate preoperative Ki-67 prediction.
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OBJECTIVE: Neoadjuvant chemotherapy (NAC) in breast cancer (BC) is being considered for a broader range of cases, including locally advanced tumors and situations where downstaging could reduce extensive surgery. Several trials have explored predictive markers of pathological complete response (pCR). The role of Ki-67 as a predictor of pCR has been demonstrated in studies. However, the cut-off remains vague, given the lack of standardization of measurement methods. The aim of our study was to evaluate the predictive value of Ki-67 in response to NAC and to identify the cut-off values that exhibit the strongest correlation with best response. MATERIALS AND METHODS: This retrospective study included 187 patients who had undergone surgery following NAC for BC at the CHU Souss Massa of Agadir between January 2020 and January 2023. Logistic regression was used to assess the correlation between Ki-67 and patients' characteristics. Optimal Ki-67 cutoff was identified by receiver operating characteristic curve. Kaplan-Meier curves were used to assess disease-free survival (DFS), and survival comparisons were assessed with the log-rank test. RESULTS: The median age was 51.8±10.7 years and 51.4% of tumors were smaller than 5 cm. Node invasion was found in 55.4%. Luminal B subtype was found in 49.7%, followed by human epidermal growth factor receptor-2 (HER-2)-positive in 27.4%, triple-negative in 14.3% and Luminal A in 8.6%. pCR occurred in 40% of patients overall. Subgroup analysis revealed a significant association between pCR and tumor size (p<0.001), lymph node involvement (p<0.001), grade 2 (p<0.001), vascular invasion (p<0.001), and positive HER-2 status (p = 0.022). In statistical analysis, pathological responses were improved in patients with Ki-67 >35% (p<0.001). DFS was 98.8% at 12 months. No statistical difference was found in DFS according to Ki-67 values and pCR status. CONCLUSION: Our results indicate that Ki-67 is a predictive marker for response in the neoadjuvant setting in BC patients. Our study showed that a Ki-67 cut-off >35% predicts a better pCR rate in response to NAC. However, this cutoff value remains controversial due to the absence of a standard method of measurement, with inter- and intra-observer variability. It would be necessary to validate this cutoff in other studies.
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BACKGROUND: Lung cancer's high prevalence and invasiveness make it a major global health concern. The Ki-67 index, which indicates cellular proliferation, is crucial for assessing lung cancer aggressiveness. Radiomics, which extracts quantifiable features from medical images using algorithms, may provide insights into tumor behavior. This systematic review and meta-analysis evaluate the effectiveness of radiomics in predicting Ki-67 status in Non-Small Cell Lung Cancer (NSCLC) using CT scans. METHODS AND MATERIALS: A comprehensive search was conducted in PubMed/MEDLINE, Embase, Scopus, and Web of Science databases from inception until April 19, 2024. Original studies discussing the performance of CT-based radiomics for predicting Ki-67 status in NSCLC cohorts were included. The quality assessment involved quality assessment of diagnostic accuracy studies (QUADAS-2), radiomics quality score (RQS) and METhodological RadiomICs Score (METRICS). Quantitative meta-analysis, using R, assessed pooled diagnostic odds ratio, sensitivity, and specificity in NSCLC cohorts. RESULTS: We identified 10 studies that met the inclusion criteria, involving 2279 participants, with 9 of these studies included in quantitative meta-analysis. The pooled sensitivity and specificity of radiomics-based models for predicting Ki-67 status in NSCLC were 0.783 (95 % CI: 0.732 - 0.827) and 0.796 (95 % CI: 0.707 - 0.864) in training cohorts, and 0.803 (95 % CI: 0.744 - 0.851) and 0.696 (95 % CI: 0.613 - 0.768) in validation cohorts. It was identified in subgroup analysis that utilizing ITK-SNAP as a segmentation software contributed to a significantly higher pooled sensitivity. CONCLUSION: This meta-analysis indicates promising diagnostic accuracy of radiomics in predicting Ki-67 in NSCLC.
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BACKGROUND: Oral verrucous lesions (OVLs) present a diagnostic challenge due to their diverse and often confusing histopathological features. Accurate differentiation is essential for improving diagnosis and predicting prognosis. In addition to assessing overall survival (OS) and disease-free survival (DFS) in verrucous squamous cell carcinoma (VSCC) and conventional OSCC, this study seeks to evaluate the expression of Mcm-2 and Ki-67 in verrucous lesions and oral squamous cell carcinoma (OSCC). These findings will be correlated with the nuclear expression of Mcm-2 and Ki-67. METHODOLOGY: Ninety tissue samples that were paraffin embedded and formalin-fixed were examined using immunohistochemistry to determine the expression of Mcm-2 and Ki-67. Data on survival and clinico-pathologic characteristics were taken from patient records. Statistical analyses were conducted using Independent T-tests, Cox regression models, and Kaplan-Meier survival analysis. RESULTS: Mcm-2 was identified as a more sensitive and prognostic marker compared to Ki-67 across the study groups. Mcm-2 overexpression was observed in all cases of verrucous hyperplasia with dysplasia, verrucous carcinoma (VC), VSCC, and conventional OSCC. The 3-year OS and DFS rates were lower in conventional OSCC (75 % and 64.3 %, respectively) compared to VSCC (90 % and 70 %). CONCLUSION: This study represents the first initiative to employ both Mcm-2 and Ki-67 as proliferative markers for distinguishing between various oral verrucous lesions. Mcm-2 proves to be a valuable marker for differentiating between potentially malignant and malignant verrucous lesions. However, further validation with larger sample sizes and longer follow-up periods is necessary to confirm its role in predicting OS and DFS.
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Background: The aim of this study was to determine whether mammographic and sonographic features of malignant breast lesions are correlated with tumor histologic grade, hormonal receptor, human epidermal growth factor receptor 2 (HER2), and Ki-67 status. Materials and Methods: In this retrospective study, imaging and histopathological findings of 187 biopsy-proven breast cancer cases from November 2019 to February 2021 were reviewed. The Chi-square test was used to examine the potential correlation between mammographic and sonographic characteristics with histopathological features such as hormonal receptor, HER2 status, Ki-67 labeling index, and histological grade. Results: We observed that microlobulated margin as well as oval/round morphology in mammograms correlate with triple-negative intrinsic subtype (P = 0.006 and P = 0.004). The presence of calcification in sonography was significantly higher in the luminal-B subtype (P = 0.002). Furthermore, ill-defined margins in mammography were significantly higher in amplified HER2 expression (P = 0.004) in the same manner as an oval/round shape in higher levels of Ki-67 (P = 0.030). Conclusion: Mammography and sonography features may reflect the biological behavior of various subtypes of breast cancer and can detect more aggressive breast cancers that can mimic benign or less malignant appearing lesions. These findings may be an excellent predictor for some subtypes like triple-negative breast cancer. Studying the range of these imaging characteristics may help in better understanding the prognosis, choosing a treatment strategy, and predicting response to treatment.
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BACKGROUND: Organized cervical cancer (CxCa) screening is the most effective secondary prevention method to decrease the disease incidence and mortality. Screening for infection with 14 high-risk HPV genotypes (hrHPV) is recommended as primary screening test. Since only ca. 6 % of HPV-positive (HPV+) women will develop a high-grade lesion in 5 years, triage is critical for risk stratification and management of colposcopy resources. Dual staining (DS) p16/Ki67 cytology is an alternative to Papanicolau cytology (PAP) for triage of HPV+women, with potential improvements in sensitivity and specificity, and optimization of colposcopy referrals. OBJECTIVES: To compare PAP vs DS cytology in terms of (i) optimization of referrals for colposcopy and (ii) risk stratification to better define the follow-up interval. STUDY DESIGN: Retrospective analysis of the CxCa screening database of Centro Hospitalar Universitário de Coimbra (CHUC), one of the centralized diagnostic laboratories for the CxCa screening program of the central region of Portugal, between July 2019 and May 2023. At CHUC, since July 2019, all samples from hrHPV+women have been triaged with liquid PAP and tested with DS cytology. RESULTS: At baseline (1032 HPV+women), 1028 women were tested with DS: 739 women were DS negative (DS-) [70.7 % with normal PAP cytology (NILM) and 29.3 % with abnormal PAP cytology (ASC-US+)], and 289 were DS positive (DS+) (1.1 % NILM and 98.6 % ASC-US+). DS positivity as referral criterion for colposcopy instead of ASC-US+would have reduced the number of colposcopies by 39.4 % overall and by 48.3 % for other 12 hrHPV, while improving the number of colposcopies per HSIL (3.9 vs. 2.4 overall and 4.9 vs. 2.9 for other 12 hrHPV). In this cohort, if the follow-up interval for women positive for other 12 hrHPV+and DS- would have been extended from 1 to 3 years, 799 follow-up consultations, 799 HPV re-tests, and 277 colposcopies (-64.7 %) would have been avoided, with an overall risk of missed HSIL lesions of 2.2 %. CONCLUSIONS: Triage with DS allows the optimization of colposcopy referrals and a safe extension of the follow-up interval to 3 years for other 12 hrHPV+/DS- women, eliminating the need for annual re-testing for many women.
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BACKGROUND: Prostate cancer (PCa) remains a significant global health issue, exhibiting a spectrum of clinical behaviours from indolent to aggressive. Biomarkers are crucial for risk assessment, treatment selection and prognosis prediction. Despite their importance, accurately evaluating PCa aggressiveness and guiding personalised treatment strategies present challenges. This review aims to evaluate biomarkers for assessing recurrence risk following radical prostatectomy, with a focus on personalised follow-up and timely intervention for high-risk patients. This review assesses the clinical significance of immunohistochemical biomarkers, including LIM domain kinase 1 (LIMK1), Antigen Kiel 67 (Ki67), PTEN and ERG, in PCa management. A comprehensive literature review examined the correlation between these biomarkers and biochemical recurrence (BCR) in patients undergoing radical prostatectomy. Our search included articles published between 2019 and 2024, yielding 87 articles, with 7 focused on the correlation between LIMK1 and BCR, 46 on Ki67 and 34 on PTEN/ERG biomarkers. After applying the exclusion criteria, 36 articles were included for review. LIMK1, a serine/threonine kinase, is highly expressed in cancers like PCa. It influences cell survival and motility through actin cytoskeleton reorganisation, correlating with poor prognosis, aggressive tumour behaviour and BCR. Similarly, Ki67, a marker of cell proliferation, predicts high-risk PCa and worse prognosis, particularly in castration-resistant cases, although its association with recurrence risk remains debated. PTEN loss and ERG fusion are prevalent genetic alterations in PCa, with PTEN loss linked to poor prognosis and ERG fusion associated with increased disease progression and BCR post-prostatectomy. Integrating these biomarkers into clinical practice can enhance risk stratification and inform personalised treatment strategies for patients with PCa. Despite promising findings, further validation studies and standardisation of detection methods are needed to ensure the clinical utility of these biomarkers. Continued research is essential to validate and optimise the clinical utility of these biomarkers, paving the way for more effective PCa management strategies and improved patient outcomes and quality of life.
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Biomarcadores de Tumor , Inmunohistoquímica , Recurrencia Local de Neoplasia , Prostatectomía , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Medición de Riesgo , Valor Predictivo de las PruebasRESUMEN
Background: Cervical cancer, primarily driven by high-risk human papillomavirus (HR-HPV) infection, ranks as the second most common cancer globally. Understanding combined infections' role, including Cervical fungi, is crucial in cervical carcinogenesis. This study aims to explore the potential correlation between HR-HPV, cervical fungi, and cervical cancer, while adjusting for various factors. Methods: The study population comprised patients undergoing colposcopy and conization due to abnormal cervical screening results. Clinical data including age, gravidity, HPV (human papillomavirus) genotypes, cervical pathology, and p16/Ki67 expression were extracted. Cervical TCT (ThinPrep Pap Test) and HPV testing are utilized for screening cervical lesions, with fungal presence suggested by TCT results. 5,528 participants were included in this study. Statistical analyses investigated associations between HPV/fungi co-infection and cervical lesions, employing multinomial logistic regression and interaction analysis. Results: Co-infection with fungi and HPV may decrease the risk of cervical lesions compared to HPV infection alone. In the co-infection group, compared with HPV infection alone, the risk of low-grade squamous intraepithelial lesions (LSIL) was reduced by 27% (OR = 0.73, 95% CI: 0.59-0.90), the risk of high-grade squamous intraepithelial lesions (HSIL) was reduced by 35% (OR = 0.65, 95% CI: 0.51-0.82), and the risk of cervical cancer was reduced by 43% (OR = 0.57, 95% CI: 0.35-0.92). The interaction analysis revealed a negative interaction between fungal and HPV infections in the development of cervical cancer (RERI = -6.25, AP = -0.79, SI = 0.52), HSIL (RERI = -19.15, AP = -0.37, SI = 0.72) and LSIL (RERI = -1.87, AP = -0.33, SI = 0.71), suggesting a sub-additive effect, where the combined effect of the two infections was less than the sum of their individual effects. This indicates that fungal infection may attenuate the promoting effect of HPV on cervical lesions. In exploring the potential mechanism, we found that the co-infection group had significantly lower p16 positivity (54.6%) compared to the HPV-only group (60.2%) (p = 0.004), while there was no statistically significant difference in Ki67 positivity. Conclusion: This study unveils the intricate relationship between cervical fungi and HPV in cervical lesions. Co-infection with fungi and HPV against cervical lesions compared to HPV infection alone, indicating a novel clinical interaction. Lower p16 positivity in co-infection hints at a protective mechanism, urging further exploration.
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The association of clinical, pathological, and immunohistochemical characteristics of papillary thyroid cancer with cause-specific mortality was analyzed in a case-control study within a cohort of patients from the Altai Regional Oncology Center. According to multivariate analysis, the independent predictors of fatal outcome within 10 years after surgery in patients living in Altai region are nuclear pattern of Hsp70 expression, thyroid capsular invasion, Ki-67 expression index >7%, and patient's age >45 years for men and >50 years for women. The prognostic model based on these features contributes to a significant improvement in the individual prognostic performance for papillary thyroid cancer in the modeling sample. The model has high statistical significance (χ2=64.73; p<0.001) and discriminative power (AUC=0.950, prediction accuracy 88.5%).
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Antígeno Ki-67 , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Humanos , Femenino , Masculino , Persona de Mediana Edad , Cáncer Papilar Tiroideo/mortalidad , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/cirugía , Cáncer Papilar Tiroideo/metabolismo , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/cirugía , Estudios de Casos y Controles , Adulto , Antígeno Ki-67/metabolismo , Antígeno Ki-67/genética , Pronóstico , Análisis Multivariante , Proteínas HSP70 de Choque Térmico/metabolismo , Carcinoma Papilar/patología , Carcinoma Papilar/mortalidad , Carcinoma Papilar/cirugía , Carcinoma Papilar/metabolismo , Inmunohistoquímica , Anciano , Biomarcadores de Tumor/metabolismoRESUMEN
BACKGROUND: Pathologists commonly employ the Ki67 immunohistochemistry labelling index (LI) when deciding appropriate therapeutic strategies for patients with breast cancer. However, despite several attempts at standardizing the Ki67 LI, inter-observer and inter-laboratory bias remain problematic. We developed a flow cytometric assay that employed tissue dissociation, enzymatic treatment and a gating process to analyse Ki67 in formalin-fixed paraffin-embedded (FFPE) breast cancer tissue. RESULTS: We demonstrated that mechanical homogenizations combined with thrombin treatment can be used to recover efficiently intact single-cell nuclei from FFPE breast cancer tissue. Ki67 in the recovered cell nuclei retained reactivity against the MIB-1 antibody, which has been widely used in clinical settings. Additionally, since the method did not alter the nucleoskeletal structure of tissues, the nuclei of cancer cells can be enriched in data analysis based on differences in size and complexity of nuclei of lymphocytes and normal mammary cells. In a clinical study using the developed protocol, Ki67 positivity was correlated with the Ki67 LI obtained by hot spot analysis by a pathologist in Japan (rho = 0.756, P < 0.0001). The number of cancer cell nuclei subjected to the analysis in our assay was more than twice the number routinely checked by pathologists in clinical settings. CONCLUSIONS: The findings of this study showed the application of this new flow cytometry method could potentially be used to standardize Ki67 assessments in breast cancer.
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Neoplasias de la Mama , Citometría de Flujo , Antígeno Ki-67 , Adhesión en Parafina , Antígeno Ki-67/metabolismo , Antígeno Ki-67/análisis , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Humanos , Citometría de Flujo/métodos , Femenino , Adhesión en Parafina/métodos , Formaldehído , Fijación del Tejido/métodosRESUMEN
Purpose: Endometrial cancer (EC) is one of the most common types of cancer affecting women. While the hematoxylin-and-eosin (H&E) staining remains the standard for histological analysis, the immunohistochemistry (IHC) method provides molecular-level visualizations. Our study proposes a digital staining method to generate the hematoxylin-3,3'-diaminobenzidine (H-DAB) IHC stain of Ki-67 for the whole slide image of the EC tumor from its H&E stain counterpart. Approach: We employed a color unmixing technique to yield stain density maps from the optical density (OD) of the stains and utilized the U-Net for end-to-end inference. The effectiveness of the proposed method was evaluated using the Pearson correlation between the digital and physical stain's labeling index (LI), a key metric indicating tumor proliferation. Two different cross-validation schemes were designed in our study: intraslide validation and cross-case validation (CCV). In the widely used intraslide scheme, the training and validation sets might include different regions from the same slide. The rigorous CCV validation scheme strictly prohibited any validation slide from contributing to training. Results: The proposed method yielded a high-resolution digital stain with preserved histological features, indicating a reliable correlation with the physical stain in terms of the Ki-67 LI. In the intraslide scheme, using intraslide patches resulted in a biased accuracy (e.g., R = 0.98 ) significantly higher than that of CCV. The CCV scheme retained a fair correlation (e.g., R = 0.66 ) between the LIs calculated from the digital stain and its physical IHC counterpart. Inferring the OD of the IHC stain from that of the H&E stain enhanced the correlation metric, outperforming that of the baseline model using the RGB space. Conclusions: Our study revealed that molecule-level insights could be obtained from H&E images using deep learning. Furthermore, the improvement brought via OD inference indicated a possible method for creating more generalizable models for digital staining via per-stain analysis.
RESUMEN
BACKGROUND: Myxofibrosarcoma is a myxoid soft tissue sarcoma showing T2 high intensity on magnetic resonance imaging. However, myxofibrosarcoma is a heterogeneous sarcoma with both myxoid and cellular portions. Magnetic resonance imaging findings were obtained MRI findings for comparison with histological and Ki-67 immunohistochemical features, in different portions of one myxofibrosarcoma. CASE PRESENTATION: Magnetic resonance imaging observations were compared with gross pathological and microscopic findings of a myxofibrosarcoma from a 50-year-old Japanese female. The Ki-67 labeling indices of different portions of the tumor, that is, the myxoid, cellular, and histologically confirmed infiltrative margin portions (pathological tail sign), were compared. The T2 low intensity area was more cellular than the T2 high intensity area, while the cellular portion had a significantly higher Ki-67 index than the myxoid portion (p = 0.0313). The portions with the pathological tail sign had a significantly higher Ki-67 labeling index than those without this sign (p = 0.0313). CONCLUSIONS: More cellular portions of a myxofibrosarcoma correspond to more areas of the tumor showing aggressive features. Furthermore, our data also support the hypothesis of high aggressiveness being associated with the pathological tail sign in myxofibrosarcoma. To our knowledge, this is the first case report to describe comparisons among the imaging findings, histological features, and Ki-67 immunohistochemistry results for different portions of one myxofibrosarcoma.