Exploration of different EGFR scores and their relationship with prognosis in patients with urothelial carcinoma with squamous differentiation.

Abstract

e16565 Background: EGFR-targeted ADCs have demonstrated preliminary efficacy in Urothelial carcinoma (UC). UC with squamous differentiation (UCSC) is typically classified as basal type, which is associated with increased expression of EGFR. This study explores the differences in EGFR expression between UCSC and pure UC by IHC and the correlation of different EGFR scores with prognosis. Methods: Patients diagnosed with UCSC from our center were collected and matched with patients with pure UC. Use IHC to compare the expression levels of HER-2 and EGFR between the 2 groups, and evaluate the differences in survival rates between these patient cohorts. The relationship between EGFR IHC and prognosis was explored using 3 methods. In method I, EGFR H-scores = (3×%IHC3+) +(2×%IHC2+) +(1×%IHC1+). In method II, EGFR high expression was defined with 3+ or 2+ staining greater than 50%, and in method III which was defined with solely 3+ staining greater than 50%. Results: A total of 67 UCSC and 12 pure UC patients were included in this study. In the 2 groups, the number of male patients were 52 (77.6%) and 9 (75.0%), patients older than 60 years were 47 (70.1%) and 10 (83.3%), the proportion of patients with initial staging as I/II/III/IV was 6/17/27/17 and 3/4/3/2, 47(70.1%) and 6 (50.0%) patients eventually developed metastasis, the mOS were 33.5 mos and not reached, respectively. None of the above characteristics showed statistical differences. Among UCSC, for HER-2 IHC, 10 patients were 3+, 17 were 2+, 15 were 1+, and 20 were negative. The H-scores range was 0-290, with the median of 7.5 and the average of 43.0. For EGFR IHC, 62 patients were 3+, 4 were 2+, and 1 was 1+. The H-scores range was 50-290, with the median of 250, and the average of 236. Among pure UC, EGFR H-scores range was 130-290, the median was 195, and the average was 196.7. The difference between the two groups was statistically significant (P = 0.026). Among UCSC, there were 43 patients with EGFR H-scores greater than 236, the mOS was 23.8 mos (95% CI 15.9-42.6 mos), for patients with H-scores less than 236, the mOS was 60.4 mos (95% CI 16.0-95.9 mos). The difference in OS between the 2 groups was statistically significant (P = 0.033). In Method II, patients with EGFR high expression were 44, the mOS was 22.1 mos (95% CI 13.6–33.5 mos), and 23 patients with low expression, the mOS was not reached (95% CI 47.1-not reached, P = 0.293). In method III, patients with EGFR high expression were 38, the mOS was 22.1 mos (95% CI 12.7–33.5 mos), and 29 patients with low expression, the mOS was 60.4 mos (95% CI 29.9–95.9mos, P = 0.119). Conclusions: Compared with pure UC, UCSC tends to have a later initial stage and is more likely to develop metastasis. UCSC has higher expression of EGFR and lower expression of HER2. In UCSC, the EGFR H-scores method is a more prognostic predictor compared to the other two methods.