EGFR EXPRESSION IN PRIMARY EPITHELIAL URINARY BLADDER TUMORS AND ITS CORRELATION WITH CLINICOPATHOLOGICAL PARAMETERS

Introduction: EGFR is over expressed in many epithelial tumors including urothelial carcinomas. Over expression of EGFR is considered as a poor prognostic marker in various studies. Thus, the present study was done to evaluate the EGFR expression in primary urothelial carcinomas and its correlation with clinicopathological parameters. Methods: This was a cross-sectional, observational study carried out between June 1, 2019 to May 31, 2020 in the Department of Pathology and Urology, Indira Gandhi Medical College, Shimla. One hundred and ninety seven patients with primary epithelial urinary bladder cancer were included. Patients with inammatory and metastatic lesions of urinary bladder and post chemoradiotherapy were excluded. The correlation between EGFR expression and the various factors like age (<60 years or ≥60 years), sex (male/female), size of tumor (< 3cm or ≥ 3cm), number of tumors (solitary/multiple) and grade (high/low) were evaluated using EpiInfoV.7 software version and chi-square test. Results: The age of patients ranged from 36 to 89 years. Male preponderance was observed. Most common clinical presentation was painless hematuria. EGFR positivity was observed in majority, 190 cases, irrespective of histological type and grade of tumor. No statistical signicant correlation was found between EGFR expression and age of patient, size of tumor, number of tumor and histological grades of urothelial tumors. Conclusion: Majority of urothelial carcinomas over expressed EGFR irrespective of their histological grade. So, targeted EGFR therapy in urothelial carcinomas can emerge as a novel therapy improving overall survival and prognosis of the patients with urothelial carcinomas.

A New Kid on the Block: Sacituzumab Govitecan for the Treatment of Breast Cancer and Other Solid Tumors

Human trophoblast cell-surface antigen-2 (Trop-2) is a membrane glycoprotein involved in cell proliferation and motility, frequently overexpressed in epithelial tumors. Thus, it represents an attractive target for anticancer therapies. Sacituzumab govitecan (SG) is a third-generation antibody-drug conjugate, consisting of an anti-Trop-2 monoclonal antibody (hRS7), a hydrolyzable linker, and a cytotoxin (SN38), which inhibits topoisomerase 1. Specific pharmacological features, such as the high antibody to payload ratio, the ultra-toxic nature of SN38, and the capacity to kill surrounding tumor cells (the bystander effect), make SG a very promising drug for cancer treatment. Indeed, unprecedented results have been observed with SG in patients with heavily pretreated advanced triple-negative breast cancer and urothelial carcinomas, and the drug has already received approval for these indications. These results are coupled with a manageable toxicity profile, with neutropenia and diarrhea as the most frequent adverse events, mainly of grades 1–2. While several trials are exploring SG activity in different tumor types and settings, potential biomarkers of response are under investigation. Among these, Trop-2 overexpression and the presence of BRCA1/2 mutations seem to be the most promising. We review the available literature concerning SG, with a focus on its toxicity spectrum and possible biomarkers of its response.

Urothelial carcinoma of the fossa navicularis successfully treated with laser ablation and distal urethrectomy: A case report

Primary urothelial carcinomas very rarely arise from the fossa navicularis of the penis. They are rarely reported in the literature, with only 13 cases reported thus far. Herein, we present the case of a 34-year-old man with bloody urethral discharge due to a mass detected by cystourethroscopy in the fossa navicularis. Biopsy confirmed the diagnosis of noninvasive urothelial carcinoma. The patient was managed successfully with two sessions of holmium laser ablation, followed by distal urethrectomy. After the treatment, the patient's erectile function and continence were preserved, and no tumor recurrence was observed after 1 year of follow-up.

Morphological predictors for microsatellite instability in urothelial carcinoma

Introduction Microsatellite instability occurs due to a series of mutations in the DNA pairing error repair (Mismatch repair; MMR) genes, which can affect germ cells as occurs in Lynch syndrome, whose patients are at high risk of developing multiple cancers. The loss of MMR protein is commonly determined by immunohistochemical studies. Although the relation between microsatellite instability and urothelial carcinomas has been widely studied, its evaluation is not currently performed in the analysis of urothelial carcinomas. Methods In this study, the microsatellite status of 139 urothelial carcinomas was analyzed and their clinicopathological characteristics were evaluated. We identified that 10.3% (13 patients) of urothelial carcinomas had loss of MMR protein expression (9 MLH1; 5 MSH2; 2 PMS2; 2 PSH6; n = 139). Results Results suggest that these tumors occur more frequently in males, are more frequently located in the bladder or ureters, and present a high tumor grade with a papillary histological pattern that does not infiltrate the lamina propria or, in the case of infiltrating tumors, that grows into perivesical tissues. Conclusions We identified patients with the aforementioned tumor characteristics as patients with a high probability of presenting loss of MMR protein expression, and consider that only these patients should undergo further immunohistochemical and molecular techniques for proper diagnosis. Therefore, we propose that the clinicopathological characteristics found in the present study could become possible markers to determine which cases should undergo additional tests.

Immunoexpression of PD-L1 and PD-1 and Its Clinicopathological Correlation in Urothelial Carcinomas

Introduction Urothelial carcinomas are the most common types of bladder tumors that have recently shown a changing trend in treatment protocols with the introduction and approval of immune checkpoint inhibitors. The most important immune checkpoint lies with the PD-1–PD-L1 axis. Although multiple drugs have been approved, there is uncertainty about patient selection criteria and diagnostic assays. Recent studies related to the laboratory-developed tests have opened up the horizon of PD-1 and PD-L1 immunohistochemistry even at resource-constrained laboratories. We propose to study these immunohistochemistry markers in our laboratory using newer clones. Materials and Methods We selected 116 consecutive cases of transurethral bladder tumor resection from our laboratory archive and applied PD-1 and PD-L1 immunohistochemistry. The study was approved by the institution's ethics committee. Results We found high expression of PD-1 and PD-L1 in urothelial carcinoma even with different cut-offs of PD-L1. Muscle invasion, lamina invasion, and grade of carcinoma had a statistically significant effect on the expression; however, age and sex did not affect the expression. Conclusion Based on our current study, we can conclude that the clones used in our study show high expression in urothelial carcinoma and can aid in patient selection and treatment protocol, irrespective of age and sex.

Utility of GATA-3 and Cytokeratin 5/6 Immunostains in Separating Condyloma Acuminatum Arising in the Urinary Tract From Non-Invasive Papillary Urothelial Carcinoma

Background Condyloma acuminatum is a squamous epithelial lesion which uncommonly involves the urinary tract. In this location, non-invasive papillary urothelial carcinoma constitutes one of the main differential diagnoses with significant prognostic and therapeutic implications. To date, no ancillary immunohistochemical stain has been described to differentiate these two entities. We assess the utility of cytokeratin 5/6 (CK5/6) and GATA-3 immunohistochemistry in distinguishing condyloma acuminatum from non-invasive papillary urothelial carcinoma. Design We reviewed 9 condylomata acuminata involving the urinary tract, 12 low-grade and 8 high-grade non-invasive papillary urothelial carcinomas. CK5/6 immunostaining was performed in all cases. GATA-3 immunostaining and low-risk human papilloma virus (HPV) chromogenic in situ hybridization was performed in all condyloma cases and 2 urothelial carcinomas with squamous differentiation. Results 8/9 condylomata acuminata were positive for low-risk HPV. All condylomata acuminata exhibited strong full-thickness cytoplasmic staining for CK5/6. In 10 of 12 low-grade non-invasive papillary urothelial carcinomas, CK5/6 expression was continuous and limited to the basal cell layer, while it was patchy and limited to the basal cell layer in all 8 high-grade non-invasive papillary urothelial carcinomas. Two low-grade non-invasive papillary urothelial carcinomas showed focal full-thickness CK5/6 expression in the areas of squamous differentiation. These 2 cases were negative for low-risk HPV. GATA-3 immunostaining was positive in all condylomata acuminata. Conclusions CK5/6 immunostaining is a useful and simple tool that can help separate low-grade and high-grade non-invasive papillary urothelial carcinomas from condyloma acuminatum involving the urothelium-lined organs. GATA-3 has no discriminatory role between condyloma acuminatum and papillary urothelial carcinomas.