Breast cancer-specific survival by clinical subtype after 7 years follow-up of young and elderly women in a nationwide cohort.

Age and tumor subtype are prognostic factors for breast cancer survival, but it is unclear which matters the most. We used population-based data to address this question. We identified 21,384 women diagnosed with breast cancer at ages 20-89 between 2005 and 2015 in the Cancer Registry of Norway. Subtype was defined using estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 (HER2) status as luminal A-like (ER+PR+HER2-), luminal B-like HER2-negative (ER+PR-HER2-), luminal B-like HER2-positive (ER+PR+/-HER2+), HER2-positive (ER-PR-HER2+) and triple-negative (TNBC) (ER-PR-HER2-). Cox regression estimated hazard ratios (HR) for breast cancer-specific 7-year survival by age and subtype, while adjusting for year, grade, TNM stage and treatment. Young women more often had HER2-positive and TNBC tumors, while elderly women (70-89) more often had luminal A-like tumors. Compared to age 50-59, young women had doubled breast cancer-specific mortality rate (HR = 2.26, 95% CI 1.81-2.82), while elderly had two to five times higher mortality rate (70-79: HR = 2.25, 1.87-2.71; 80-89: HR = 5.19, 4.21-6.41). After adjustments, the association was non-significant among young women but remained high among elderly. Young age was associated with increased breast cancer-specific mortality among luminal A-like subtype, while old age was associated with increased mortality in all subtypes. Age and subtype were strong independent prognostic factors. The elderly always did worse, also after adjustment for subtype. Tumor-associated factors (subtype, grade and stage) largely explained the higher breast cancer-specific mortality among young. Future studies should address why luminal A-like subtype is associated with a higher mortality rate in young women.

Comparison of cell cycle progression score with two immunohistochemical markers (PTEN and Ki-67) for predicting outcome in prostate cancer after radical prostatectomy.

PURPOSE: Previous studies of the cell cycle progression (CCP) score in surgical specimens of prostate cancer (PCa) in patients treated by radical prostatectomy (RP) demonstrated significant association with time to biochemical recurrence (BCR). In this study, we compared the ability of the CCP score and the expression of PTEN or Ki-67 to predict BCR in a cohort of patients treated by RP. Finally, we constructed the best predictive model for BCR, incorporating biomarkers and relevant clinical variables. MATERIALS AND METHODS: The study population consisted of 652 PCa patients enrolled in a retrospective cohort and who had RP surgery in French urological centers from 2000 to 2007. RESULTS: Among the 652 patients with CCP scores and complete clinical data, BCR events occurred in 41%, and the median time from surgery to the last follow-up among BCR-free patients was 72 months. In univariate Cox analysis, the continuous CCP score and positive Ki-67 predicted recurrence with a HR of 1.44 (95% CI 1.17-1.75; p = 5.3 × 10-4) and 1.89 (95% CI 1.38-2.57; p = 1.6 × 10-4), respectively. In contrast, PTEN expression was not associated with BCR risk. Of the three biomarkers, only the CCP score remained significantly associated in a multivariable Cox model (p = 0.026). The best model incorporated CAPRA-S and CCP scores as predictors, with HRs of 1.32 and 1.24, respectively. CONCLUSION: The CCP score was superior to the two IHC markers (PTEN and Ki-67) for predicting outcome in PCa after RP.

Characterization of Breast Tumors from MR Images Using Radiomics and Machine Learning Approaches.

Determining histological subtypes, such as invasive ductal and invasive lobular carcinomas (IDCs and ILCs) and immunohistochemical markers, such as estrogen response (ER), progesterone response (PR), and the HER2 protein status is important in planning breast cancer treatment. MRI-based radiomic analysis is emerging as a non-invasive substitute for biopsy to determine these signatures. We explore the effectiveness of radiomics-based and CNN (convolutional neural network)-based classification models to this end. T1-weighted dynamic contrast-enhanced, contrast-subtracted T1, and T2-weighted MR images of 429 breast cancer tumors from 323 patients are used. Various combinations of input data and classification schemes are applied for ER+ vs. ER-, PR+ vs. PR-, HER2+ vs. HER2-, and IDC vs. ILC classification tasks. The best results were obtained for the ER+ vs. ER- and IDC vs. ILC classification tasks, with their respective AUCs reaching 0.78 and 0.73 on test data. The results with multi-contrast input data were generally better than the mono-contrast alone. The radiomics and CNN-based approaches generally exhibited comparable results. ER and IDC/ILC classification results were promising. PR and HER2 classifications need further investigation through a larger dataset. Better results by using multi-contrast data might indicate that multi-parametric quantitative MRI could be used to achieve more reliable classifiers.

Malignant mesothelioma: A clinicopathological study of 76 cases with emphasis on immunohistochemical evaluation along with review of the literature.

INTRODUCTION: Malignant mesothelioma is an aggressive neoplasm arising from serosal lining and has a poor prognosis. Definite diagnosis requires confirmation through a biopsy; however, it is sometimes difficult on microscopic evaluation alone and requires the use of a wide panel of immunohistochemical markers. So, immunohistochemistry (IHC) is of paramount importance and must be routinely used for a definite diagnosis. Till date, very few studies on morphology and detailed IHC markers of mesothelioma have been reported from India. AIMS: To analyze the histomorphological findings of malignant mesothelioma, study the utility and role of the various immunohistochemical markers. MATERIAL AND METHODS: A total of 76 cases of mesotheliomas diagnosed at a tertiary cancer center in Udaipur were analyzed retrospectively from January 2015 to January 2020. Comprehensive data were analyzed including demographic, clinical, radiological, histopathological features along with a wide panel of IHC markers. RESULTS: Mesothelioma occurs over a wide age range from 40 to 70 years. It most commonly involved pleura in 68 cases (89.47%) with very few cases from the peritoneum. On computed tomography (CT) scan, nodular pleural or peritoneal thickening was present. On microscopy, the most common histopathological type was epithelioid mesothelioma (58 cases, 74.3%) followed by sarcomatous (9 cases, 12.8%), deciduoid (6 cases, 8.6%), and 3 cases of biphasic (4.3%). On IHC, WT1, mesothelin, and calretinin markers were positive in 85.91%, 80%, and 93.33% cases of mesothelioma, respectively. Other markers were helpful to rule out differential diagnosis in difficult scenarios. CONCLUSION: Therefore, the correlation of histopathology with clinico-radiological findings and judicious use of a panel of IHC markers is required for routine evaluation and definite diagnosis. IHC is also useful in situations with similar morphological spectrum in specific locations.

Role of MLC901 in increasing neurogenesis in rats with traumatic brain injury.

BACKGROUND: Traumatic brain injury is a dangerous life threatening condition. This study examines the role of MLC901 in increasing neurogenesis. The aim of this study was to demonstrate the role of MLC901 in increasing neuron cell (neurogenesis) in rat with traumatic brain injury using the synaptophysin marker. METHODS: The synaptophysin levels were measured as a marker for neuron cell (neurogenesis) of brain nerve cells in Sprague-Dawley rats aged 10-12 weeks, weighing 200-300 g. All rats (n = 10) were performed as traumatic brain injury using The Modified Marmourou Model, then they were divided into 2 group, one group was given MLC901 (n = 5) and the other group was not given MLC901 (n = 5). The synaptophysin levels in both groups were assessed after 6 weeks and also carried out an examination of immnuhistochemical from the brain tissue of both groups. RESULTS: There was an increase in the number of neuron cells as evidenced by synaptophysin ihc staining in the rats given MLC 901 (Neuroaid II) compared to those without MLC 901. Synaptophysin levels were lower in the control group than in the MLC 901 group (81.6, SD: 13.52 vs 118.4, SD: 12.198, p = 0.062). CONCLUSION: These research suggest that MLC901 can increase neurogenesis in traumatic brain injury and also appeared as synaptophysin antibody that binding to cytoplasm of neuronal cells in the rat brain.

Response to immunohistochemical markers' conversion after neoadjuvant chemotherapy in breast cancer patients: association between imaging and histopathologic analysis.

BACKGROUND: Breast ultrasound and mammography were used in the detection of residual tumor after neoadjuvant chemotherapy. The aim of this study was to evaluate the correlation between clinical and pathological responses with breast density and IHC marker conversion to understand how this information might be used in the future to direct treatment. METHODS: We included 119 patients who underwent CNB and followed NACT. The breast density assessment was based on the mammography examination performed at the time of diagnosis. We evaluated the clinical and pathological responses to NACT by the UICC and Miller-Payne grading systems, respectively. RESULTS: Of 119 patients who met the inclusion criteria, patients with high pre-treatment IHC markers levels showed higher expression of IHC markers regardless of the post-treatment IHC marker level at baseline. However, breast and node tumor sizes before and after NACT were negatively correlated with hormone receptor conversion and positively correlated with Ki-67 conversion (P < 0.05). Patients with low BD were more likely to have a cCR, pCR, TNBC, and postmenopausal status than those with a high BD (P < 0.05). BD was significantly associated with PR and Ki67 conversion but not ER conversion. CONCLUSION: Our prospective observational study demonstrated that IHC marker conversion could be used to identify lesion size changes and BD. We also found that a high BD was linked to clinical and pathological responses, molecular subtype, and menopausal status. In the future, additional studies are required to validate the predictive value identified by this research.

Conversion of immunohistochemical markers and breast density are associated with pathological response and prognosis in very young breast cancer patients who fail to achieve a pathological complete response after neoadjuvant chemotherapy.

PURPOSE: Patients younger than age 35 that fail to achieve a pathologic complete response (pCR) after Neoadjuvant chemotherapy (NACT) tend to have worse long term outcomes. The purpose of our study was to assess the correlation between the conversion of immunohistochemical (IHC) markers and breast density and investigate their association with pathological response and prognosis. METHODS: We included 119 patients younger than age 35 who failed to achieve a pCR after NACT in this analysis. We evaluated the clinical and pathological response to NACT by the Union for International Cancer control (UICC) and the Miller-Payne grading (MPG) systems, respectively. A breast density assessment was applied via mammography examination at the time of diagnosis. MPG and breast density (BD) have been combined to define a specific classification of three risk levels to evaluate the prognosis of these patients. RESULTS: The diameter changes of the tumors and lymph nodes were negatively associated with hormone receptor conversion and positively correlated with Ki67 conversion. A significantly large size change was observed in the groups demonstrating conversion from HER-2 (+) to (-). The variation level of IHC markers was related to MPG and BD and was associated with the survival rate of the patients. Patients with a high breast density and low Miller-Payne grading after NACT had a higher risk of distant metastases or local recurrences. CONCLUSION: ER, PR and Ki67 conversion are closely related to MPG, while PR and Ki67 conversion are closely related to BD. While ER and PR conversion are independent and significant predictors of disease free survival (DFS) and overall survival (OS), HER-2 and Ki67 conversion are only significant for DFS. This risk factor grouping provides a useful index to evaluate the risk of young women with breast cancer who fail to achieve a pCR.