Prevalence of biological types of breast cancer and their influence on disease staging and therapeutic management - a single-center study.

According to the St. Gallen 2011 consensus, proper qualification of breast cancer patients for treatment requires taking into consideration the division into biological types of neoplasms. The goal of this work was to assess the prevalence of all biological types of breast cancer in the population of Kuyavian-Pomeranian province. We determined the influence of particular types of neoplasms on the degree of disease progression and the choice of therapeutic management. The study was conducted on a group of 2653 patients treated surgically due to malignant breast tumors in the Oncology Centre in Bydgoszcz. In the analyzed clinical material we determined the biological type of cancer as well as other prognostic factors. The most commonly identified types of cancer were luminal B1 type (38.4%) and luminal A type (27.4% of cases), followed by a triple-negative type, luminal B2 type and HER2-positive type (respectively: 11.4%, 10.2%, and 6.9% of patients). Estrogen receptors were present in 81.1% and progesterone receptors in 71.4% of subjects. HER2 overexpression was identified in 17.3% of patients. Routine use of a biology-based division into cancer types influences the choice of anti-cancer treatment. Diagnosis of luminal A type of tumor more commonly than other biological types of cancer coexists with lower clinical and pathological disease staging. It allows for more frequent use of sparing surgical techniques in patients. It also makes systemic neoadjuvant chemotherapy unnecessary in the majority of patients (differences in such cases exhibit statistical significance of p < 0.0001).

High MAL2 expression predicts shorter survival in women with triple-negative breast cancer.

INTRODUCTION: Due to its lack of conventional surface receptors, triple-negative breast cancer (TNBC) is inherently resistant to most targeted therapies. MAL2 overexpression prompts endocytosis, conferring resistance to novel therapeutics. This study explores the role of MAL2 and PD-L1 in TNBC patients' prognosis. METHODS: We performed immunohistochemical analysis on 111 TNBC samples collected from 76 patients and evaluated the expression of MAL2 and PD-1. We expanded the study by including The Cancer Genome Atlas (TCGA) cohort. RESULTS: MAL2 expression did not correlate with stage, grade, tumor size, lymph node invasion, metastasis, and PD-1 expression. Patients with high MAL2 had significantly lower 5-year survival rates (71.33% vs. 89.59%, p = 0.0224). In the tissue microarray cohort (TMA), node invasions, size, recurrence, and low MAL2 (HR 0.29 [CI 95% 0.087-0.95]; p < 0.05) predicted longer patients' survival. In the TCGA cohort, patients with low MAL2 had significantly longer overall survival and disease-specific survival than patients with high MAL2. Older age and high MAL2 expression were the only independent predictors of shorter patient survival in the BRCA TCGA cohort. CONCLUSION: High MAL2 predicts unfavorable prognosis in triple-negative breast cancer, and its expression is independent of PD-1 levels and clinicopathological features of TNBC.

Diagnostic biopsy does not accurately reflect the PD-L1 expression in triple-negative breast cancer.

PD-L1 expression is known to predict the benefits of immune checkpoint inhibitor therapy for triple-negative breast cancer (TNBC). We examined whether the PD-L1 expression evaluated in biopsy specimens accurately reflects its expression in the whole tumor. Immunohistochemistry was performed on 81 biopsy and resection specimens from patients with TNBC to determine their PD-L1 status. We found PD-L1-positive tumors in 23 (28%) biopsy specimens and primarily PD-L1-negative tumors in 58 (72%). The PD-L1 status was reevaluated in matching postoperative specimens of primarily PD-L1-negative tumors. Of them, 31% (18/58) were positive, whereas 69% (40/58) were negative. Considering the pre- and postoperative analyses, 41 (51%) patients had PD-L1-positive tumors, while 40 had PD-L1-negative tumors. We found 18 (22%) more PD-L1-positive tumors while examining the resection specimens compared to biopsies, and the difference was statistically significant (p = 0.0038). Diagnostic biopsies do not fully reflect the PD-L1 expression in TNBC. Our results suggest that a significant subset of TNBC patients may be misclassified as PD-L1-negative and disqualified from anti-PD-L1 therapy.

The prognostic role of p53 and its correlation with CDK9 in urothelial carcinoma.

PURPOSE: The mutation of p53 is considered a pivotal step in bladder cancer pathogenesis. Recently, distinct interactions between p53 and CDK9, a transcription regulator, have been described. In this work, we explored the prognostic role of p53 expression and evaluated its associations with CDK9 in urothelial carcinoma. MATERIALS AND METHODS: The research group consisted of 67 bladder cancer samples and 32 normal urothelial mucosa samples. All specimens were analyzed using ImageJ and the IHC profiler plugin. To validate the results, 406 cases from The Cancer Genome Atlas database were analyzed. RESULTS: P53 and CDK9 are overexpressed in urothelial cancer tissues when compared to normal urothelial tissues (p < 0.05). High p53 expression was observed in metastatic tumors and tumors with high CDK9 expression (p < 0,05). High p53 expression was predictive for shorter survival in patients with non-muscle-invasive bladder cancer (HR = 0.107 [0.012-0.96]; p = 0.046) but did not correlate with prognosis in the muscle-invasive group. In high CDK9 cancers, high p53 expression correlated with the occurrence of high-grade and muscle-invasive tumors (p < 0.05). CONCLUSION: High expression of p53 correlates with unfavorable clinical features of bladder cancer. CDK9 is associated with the expression of p53, possibly through interactions with p53 inhibitors. Since the blockade of CDK9 in other malignancies reactivates wild-p53 activity, confirming the crosstalk between p53 and CDK9 in bladder cancer may be another step to explain the mechanism of tumor progression in its early stages.