Investigation of MTAP and BAP1 staining loss and P16/CDKN2A deletion in pleural cytology specimens and its role in the diagnosis of mesothelioma.

BACKGROUND: Mesothelioma is a malignant neoplasm with a poor survival rate. We aimed to investigate the importance of BAP1, MTAP (IHC), and p16/CDKN2A homozygous deletion (FISH) in cytologic material obtained from pleural effusion sampling, which is a less invasive procedure in the diagnosis of mesothelioma. METHODS: Our study discussed pleural cytology samples of cases with histopathologically proven mesothelioma diagnoses between 2017 and 2022. As the control group, materials that had pleural effusion sampling for other reasons and reactive mesothelial hyperplasia were included in the study. Cell blocks prepared from these materials were subjected to fluorescent in situ hybridization for p16/CDKN2A homozygous deletion and immunohistochemistry for BAP1 and MTAP. RESULTS: The specificity of the P16/CDKN2A homozygous deletion in diagnosing mesothelioma is 100%. Its sensitivity is 68.75%. The specificity of BAP1 immunohistochemical nuclear expression loss is 95%, while the sensitivity is 60%. Loss of nuclear expression of MTAP alone has the lowest specificity and sensitivity, with a specificity of 86% and a sensitivity of 43%. The highest sensitivity is reached when BAP1 loss and p16/CDKN2A homozygous deletion are evaluated together, increasing to 81%. The specificity is 95%. CONCLUSION: It has been determined that any marker alone cannot be used for a definitive mesothelioma diagnosis in pleural effusion cytological specimens; however, sensitivity increases in some combinations. The combination of BAP1 immunohistochemistry and p16/CDKN2A homozygous deletion detected by FISH, which has a higher specificity and sensitivity, can be routinely used in the diagnosis of mesothelioma under the guidance of clinical and radiologic information.

Prognostic significance of tumor budding in muscle invasive urothelial carcinomas of the urinary bladder.

OBJECTIVE: The aim of the present study was to analyze the prognostic significance of tumor budding in muscle-invasive urothelial carcinomas of the urinary bladder, and also to determine an optimal threshold value in evaluation. PATIENTS AND METHODS: The study included 108 patients diagnosed with muscleinvasive conventional urothelial carcinoma between 2010 and 2020. Tumor budding was evaluated on H&E-stained slides. The critical tumor budding number was determined with the "receiver operating characteristics (ROC)" curve. Cases with a tumor budding number of ≤6 were categorized as low, and cases with >6 as high tumor budding. RESULTS: The univariate Cox proportional hazards regression model for recurrence-free survival showed that lymphovascular invasion (P = 0.001), tumor budding (P = 0.012), pT stage (T4 vs. T2) (P = 0.005), and lymph node metastasis (P = 0.009) were significantly associated with recurrence-free survival. The multivariate Cox proportional hazards regression model utilizing backward stepwise (wald) method revealed that only LVI (P = 0.001) was independent risk factor for recurrence-free survival. The univariate Cox analysis showed that lymphovascular invasion (P = 0.001), tumor budding (P = 0.004), pT stage (T4 vs. T2) (P = 0.003), and lymph node metastasis (P = 0.001) were significantly associated with overall survival. The multivariate Cox analysis (backward stepwise (wald) method) revealed that tumor focality (P = 0.018), pT stage (T4 vs. T2) (P = 0.015), and lymphovascular invasion (P = 0.002) were independent factors for overall survival. CONCLUSIONS: Our findings suggested that the evaluation of tumor budding may be a useful parameter for predicting outcome in patients with muscle-invasive bladder cancer.

Prognostic Importance of Tumor Deposits in the Ipsilateral Axillary Region of Breast Cancer Patients.

Tumor deposits (TD) are irregular discrete tumor masses in adipose tissue, discontinuous from the primary tumor, that are described in various cancers. The incidence and/or prognostic value of TD in breast carcinomas have not been studied so far. We reevaluated 145 breast cancer patients, diagnosed and treated between 2001 and 2006 at our institution for the presence and incidence of TD. Histologic type, grade, size of the primary tumor, estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 status of the tumor, and presence of peritumoral lymphovascular invasion were included in the data. TD were detected in 42 cases (29.0%). The mean age of the patients was 52.2 years (27-82). Most patients (79.3%) had either invasive carcinoma of no special type (NST) or invasive lobular carcinoma, and most tumors (86.9%) were either grade 2 or 3. After excluding TD from the number of metastatic lymph nodes, the pN status of 9 patients changed. Univariate analysis of 110 patients with follow-up information revealed that the new pN status (p = 0.036), presence of local recurrence (p = 0.016) and TD (p = 0.003) were significantly correlated with distant metastases. The median follow-up of the patients was 84 months (5-161), 10-year disease-free survival and overall survival were 67.2% and 73.7%, respectively. In multivariate analysis, presence of TD remained independently associated with distant metastasis (p = 0.002). The probability of distant metastasis was 3.3 times higher in patients with TD. These results emphasize that TD are present in breast cancer patients, and that their presence should warn the clinician in terms of possible distant metastasis. Therefore, presence of TD, the evaluation of which is neither time consuming nor require sophisticated methods, should be included in pathology reports.