Probes for PTEN

Primary female urethral carcinoma (PUC-F) accounts for less than 1% of all genitourinary malignancies and comprises a histologically diverse group of tumors that are usually associated with poor prognosis. The carcinomas documented at this site include adenocarcinoma (clear cell adenocarcinoma, columnar cell carcinoma, and Skene gland adenocarcinoma), urothelial carcinoma (UCa), and squamous cell carcinoma (SCC). Recent studies have shown adenocarcinomas to be the most common type of primary urethral carcinoma in females. As most of the urethral carcinomas morphologically resemble carcinomas arising from surrounding pelvic organs or metastases, these should be ruled out before making the diagnosis of PUC-F. These tumors are currently staged according to the 8th edition of the American Joint Committee on Cancer (AJCC) staging system. However, the AJCC system has limitations, including the staging of tumors involving the anterior wall of the urethra. Staging systems like the recently proposed histology-based female urethral carcinoma staging system (UCS) takes into account the unique histological landmarks of the female urethra to better stratify pT2 and pT3 tumors into prognostic groups, that correlate with clinical outcomes including recurrence rates, disease-specific survival and overall survival. Further larger multi-institutional cohorts are however required to validate the results of this staging system. There is very limited information regarding the molecular profiling of PUC-F. Thirty-one percent of clear cell adenocarcinomas have been reported to show PIK3CA alterations, whereas 15% of adenocarcinomas show PTEN mutations. Higher tumor mutational burden and PD-L1 staining have been reported in UCa and SCC. Although multimodality treatment is usually recommended in locally advanced and metastatic disease, the role of immunotherapy and targeted therapy is promising in select PUC-F cases.