Presentation Authors: Tetsutaro Hayashi*, Kazuhiro Sentani, Hiroshima, Japan, Kenichiro Ikeda, Vancouver, Canada, Keisuke Goto, Hawaii, HI, Htoo Zarni Oo, Vancouver, Canada, Hamidreza Abdi, Ottawa, Canada, Shunsuke Shinmei, Shogo Inoue, Jun Teishima, Wataru Yasui, Hiroshima, Japan, Peter C Black, Vancouver, Canada, Akio Matsubara, Hiroshima, Japan
Introduction: Despite a similar histologic appearance, upper tract urothelial carcinoma (UTUC) and bladder cancer (BC) have some clinico-pathologic differences. Here we compared the immunohistochemical classification of UTUC and BC using the urothelial differentiation markers Uroplakin3 (UPK3), GATA3 and Cytokeratin5/6 (CK5/6).
Methods: The study population consisted of 120 patients with pTa-4 UTUC treated with radical nephroureterectomy without neoadjuvant chemotherapy. Tissue sections from nephroureterectomy were stained for UPK3, GATA3 and CK5/6. Positive staining for these markers was defined by any cancer cell staining for UPK3, >20% of cancer cells staining for GATA3, or all layers staining for CK5/6. We compared these results to a cohort of 115 patients with muscle invasive BC.
Results: In normal urothelium of upper urinary tract, UPK3 expression was observed only in umbrella cells, while CK5/6 expression was detected only in the basal layer. GATA3 expression was detected in almost all layers but its expression was highest in intermediate cells. These staining patterns were the same as those in BC. UPK3, GATA3, and CK5/6 were positive in 36 (30%), 105 (88%) and 27 (22%) of all UTUC cases, respectively. Almost all UPK3+ cases (94%) and CK5/6- cases (98%) were GATA3+. We therefore classified three groups: differentiated (DG: UPK3+; n=33), intermediate (IG: UPK3- and GATA3+; n=58) and undifferentiated (UG: GATA3- or CK5/6+; n=29). The rates of DG/IG/UG were 70/57/52% in papillary morphology (P=0.32), 3/5/17% in histological variants (P=0.07), 24/33/48% in histological grade 3 (P=0.13), and 33/59/62% in pT3-4 tumors (P=0.03), respectively. Similar correlations were observed for BC. Cancer specific survival (CSS) at 10 years in DG/IG/UG was 84/75/59% (P=0.14), with prognosis in DG better than UG (P=0.034). In multivariable analysis, histological grade 3(P < 0.01), but not IHC classification (P=0.25), was an independent predictor of poor prognosis. The rates of FGFR3, HER2 and EGFR expression, which are potential therapeutic targets, were 39/40/10%, 15/26/3% and 9/10/21% in DG, IG and UG, respectively. FGFR3 and HER2 expression were higher in DG and IG (P=0.0046 and 0.022) than in UG, which demonstrated the same tendency in BC.
Conclusions: The expression of urothelial differentiation markers was similar in both UTUC and BC. A simple IHC classification of UTUC may enhance patient risk stratification, which could be useful in clinical practice.