CLIN I C AL
Netto Publishes
3 Articles
DR. GEORGE NETTO, Professor and Chair, Department of Pathology, had two papers published last spring in the journal Human Pathology, and one in Modern Pathology.
THE
1 ST , “Targeted Sequencing of Plasmacytoid Urothelial Carcinoma Reveals Frequent TERT Promoter Mutations,” was published in the March 2019 issue, Volume 85. The article’s summary follows: “Activating mutations in the promoter of the telomerase reverse transcriptase (TERT) gene are the most common genetic alterations in urothelial carcinoma (UC) of the bladder and upper urinary tract. Although the cadherin 1 (CDH1) gene is commonly mutated in the clinically aggressive plasmacytoid variant of urothelial carcinoma (PUC), little is known about their TERT promoter mutation status. A retrospective search of our archives for PUC and UC with plasmacytoid and/or signet ring cellfeatures (2007-2014) was performed. Ten specimens from 10 patients had archived material available for DNA analysis and were included in the study. Intratumoral areas of nonplasmacytoid histology were also evaluated when present. Samples were analyzed for TERT promoter mutations with Safe-SeqS, a sequencing error-reduction technology, and sequenced using a targeted panel of the 10 most commonly mutated genes in bladder cancer on the Illumina MiSeq platform. TERT promoter mutations were detected in specimens with pure and focal plasmacytoid features (6/10). Similar to conventional UC, the predominant mutation identified was g.1295228C>T. In heterogeneous tumors with focal variant histology, concordant mutations were found in plasmacytoid and corresponding conventional, glandular, or sarcomatoid areas. Co-occurring mutations in tumor protein p53 (TP53, 2 cases) and kirsten rat sarcoma (KRAS) viral proto-oncogene (1 case) were also detected. TERT promoter mutations are frequently present in PUC,
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which provides further evidence that TERT promoter mutations are common events in bladder cancer, regardless of histologic subtype, and supports their inclusion in any liquid biopsy assay for bladder cancer.” MARIA DEL CARMEN RODRIGUEZ PENA, M.D., postdoctoral fellow, UAB Pathology, is also an author on the article.
T HE 2 N D
article entitled, “Tumor Immune Microenvironment in Non-Muscle-Invasive Urothelial Carcinoma of the Bladder,” was published in the July 2019 issue of Human Pathology, Volume 89. The summary states, “Immunotherapy has gained significance in a variety of tumor types including advanced urothelial carcinoma. Noninvasive urothelial lesions have been treated with intravesical Bacillus-Calmette-Guerin (BCG) for decades. Given treatment failure in a subset of these tumors, ongoing clinical trials investigating the role of checkpoint inhibitors are actively pursued in this group of patients. The present study aims to delineate PD-L1, CD8, and FOXP3 expression in tumor microenvironment in non– muscle-invasive urothelial carcinoma samples obtained via sequential biopsies and to assess its potential role in predicting disease outcome.
Cases with >1% and> 5% PD-L1 expression in tumor cells showed lower relative risk (RR) to recur at any subsequent biopsy compared with those with lower PD-L1 expression (RRs, 0.83 [P = .009] and 0.81 [P = .03], respectively). Cases with higher expression of FOXP3 in peritumoral lymphocytes were at lower risk for tumor grade progression at any biopsy (RR, 0.2; P = .02). Tumors with FOXP3/ CD8 expression ratio of >1 in intratumoral lymphocytes had lower risk of grade progression (RR, 0.28; P = .04).
