Prognostic value of galectin-1 and galectin-3 expression in local urothelial bladder cancer.

Abstract

e16520 Background: Galectin-1 (Gal-1) and Galectin-3 (Gal-3) are carbohydrate binding proteins which regulate cellular adhesion, proliferation, and apoptosis in solid tumors . Prior studies have reported that Gal-3 expression is associated with non-muscle invasive UC progression to muscle invasive disease. Therefore, we assessed whether UC Gal-1 and Gal-3 protein expression in cystectomy specimens was prognostic for overall survival (OS) or recurrence free survival (RFS). Methods: Tissue microarrays (TMA) were generated from chemotherapy naïve cystectomy specimens. Biopsies included benign urothelium, noninvasive papillary UC (Ta), UC in situ (Tis), and invasive UC (p1-pT4: INV). Gal-1 and Gal-3 IHC expression was scored by intensity (0-3) and % of cells staining positive (0-100). An H-score (product of % and intensity) was utilized for analysis. Clinical data including pathologic T stage, N stage, surgical margins, tumor size, and Charlson Comorbidity Index (CCI) were included in multivariable analysis. Results: 656 biopsies were evaluated from 301 patients. 198 (30%) were from benign urothelium, 28 (4%) Ta, 178 (27%) Tis, and 252 (38%) were INV. With a median follow up of 64 months, median OS was 47.5 mo and median RFS was 38.4 mo. Gal-1 H-score was significantly higher in INV specimens than non-INV specimens, and the inverse relationship was found with Gal-3 (median Gal-1 H-score was 0 across non-invasive tissue types and 200 in invasive, p < 0.01 and median Gal-3 score was 270 across non-invasive tissue types and 70 in invasive, p < 0.01). In multivariable analysis, T stage, N stage, margins, tumor size, PCV pre-op and CCI score were prognostic of OS and RFS. Gal-1 and Gal-3 H-scores were not predictive of RFS (Gal-1: HR 1.0, p = 0.67, Gal-3: HR 1.0, p = 0.25) or OS (Gal-1: HR 1.0, p = 0.71, Gal-3: HR 1.0, p = 0.37). Intra-tumoral Gal-1 and Gal-3 expression heterogeneity was observed. 203 (67%) patients had 2 or more tissue specimens and of these, 99 (49%) had discordant H-scores at the same level of invasion. Conclusions: In this cohort, both Gal-1 and Gal-3 expression correlated with biopsy T stage; however, the highest intra-tumor H-score per specimen did not independently predict for RFS or OS. This result differs from prior observations from smaller cohorts that showed an association between Gal-3 expression and RFS, suggesting that intra-tumoral Gal-1/Gal-3 heterogeneity may confound the study of Gal-1 and Gal-3 as a potential biomarker in UC. The biological significance of intra-tumoral Gal heterogeneity in UC merits further investigation.