Molecular profiling of aggressive variant urothelial carcinoma.

• DOI: 10.1200/jco.2019.37.7_suppl.378
• Publication Date: 2019-03-07T21:27:12Z
• Authors: Chethan Ramamurthy; David Arguello; Fern Anari; Pooja Ghatalia; Matthew R. Zibelman; Elizabeth R. Plimack; Earle Frederick B...; Thomas F. Hogan; Nancy Ann Dawson; Ralph J. Hauke; Jeanny B. Aragon-...; Daniel A. Vaena; Elisabeth I. Heath; Daniel M. Geynisman
• Keywords: ARID1A; CISH

378 Background: The WHO recognizes multiple variant histologies of urothelial carcinoma (vUC), many which have been associated with poor outcomes compared (UC). We aimed to explore molecular differences between aggressive vUC and UC. Methods: 23 micropapillary (MP), 16 plasmacytoid (P), sarcomatoid (S), 7 nested (N), 6 clear cell (CC), 2 giant (GC) specimens were tested 2012 2018 via a multiplatform profiling service (Caris Life Sciences, Phoenix, AZ) consisting gene sequencing (next generation [NGS]), amplification (CISH or NGS), protein expression (immunohistochemistry [IHC]). Findings 435 control UC using the Chi-square test. Results: 84% samples from primary tumor. Alterations identified are summarized in Table 1, notable for high rates TP53 mutations across histologic subtypes, varying RB1, ERBB2 FGFR mutations, overall low DNA damage repair (DDR) (29 genes reported) except S. There more ARID1A detected MP than (100% [3 specimens] v. 41.3%, p=0.044), CDH1 P (50% [4 2%, p<0.001). CISH (HER2) was seen 27.3% only 10.4% (p=0.005). Compared UC, PD-L1 IHC (SP142 assay) positive (>5%) proportion S (55.6%, p=0.002) but lower other (e.g. absent P). Tumor mutational burden (TMB) vUC: 18.4% vs. 14.3% MP, 0% P, 16.7% Conclusions: Aggressive histology UCs differential profile aberrations potential targets such as HER2 DDR well immunotherapy biomarkers. Further studies needed confirm these findings, may support therapy development rare, subtypes. Aberrations (%) Variant Histology [Table: see text]