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

Autor:	Zhu J; Levine Cancer Institute, Atrium Health, Charlotte, NC, USA., Livasy C; Carolinas Pathology Group, Charlotte, NC, USA., Donahue EE; Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, NC, USA., Symanowski JT; Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, NC, USA., Grigg CM; Levine Cancer Institute, Atrium Health, Charlotte, NC, USA., Brown LC; Levine Cancer Institute, Atrium Health, Charlotte, NC, USA., Matulay JT; Levine Cancer Institute, Atrium Health, Charlotte, NC, USA., Kearns JT; Levine Cancer Institute, Atrium Health, Charlotte, NC, USA., Raghavan D; Levine Cancer Institute, Atrium Health, Charlotte, NC, USA., Burgess EF; Levine Cancer Institute, Atrium Health, Charlotte, NC, USA., Clark PE; Levine Cancer Institute, Atrium Health, Charlotte, NC, USA.
Jazyk:	angličtina
Zdroj:	Translational andrology and urology [Transl Androl Urol] 2023 Feb 28; Vol. 12 (2), pp. 228-240. Date of Electronic Publication: 2023 Feb 07.
DOI:	10.21037/tau-22-494
Abstrakt:	Background: Galectin-1 (Gal-1) and Galectin-3 (Gal-3) are carbohydrate binding proteins with a wide range of biological activity, including regulation of cellular adhesion, proliferation, and apoptosis in solid tumors. Prior small studies have reported that Gal-3 expression is associated with progression of disease in urothelial carcinoma (UC), from non-muscle invasive UC progression to muscle invasive UC. We assessed Gal-1 and Gal-3 protein expression H-score utilizing a tissue microarray (TMA) created from 301 cystectomy specimens. Methods: Immunohistochemistry for Gal-1 and Gal-3 was performed on TMA generated from tumor blocks from chemotherapy naïve cystectomy specimens. The variable of interest, H-score, was defined as the product of the percentage of cells staining positive (0-100) and intensity score (0-3) scored by a single pathologist. Survival end points were analyzed using Kaplan-Meier and Cox Proportional Hazards methods. Clinical data including Charlson Comorbidity Index (CCI), pathologic tumor (T) stage, tumor size, node stage, and surgical margins, were included in multivariable analysis. Results: We found that Gal-1 and Gal-3 expression correlated with intratumoral T stage (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). However, the highest intratumoral H-score per cystectomy core did not independently predict for recurrence-free survival (RFS) (Gal-1: HR =1.02, P=0.44, Gal-3: HR =1.01, P=0.65) or OS (Gal-1: HR =1.02, P=0.44, Gal-3: HR =1.01, P=0.72) in this cohort. Significant intratumoral heterogeneity was present for both Gal-1 and Gal-3, with an average difference between the highest and lowest H score was 95 for Gal-1 and 109 for Gal-3 for cystectomy specimens with more than one biopsy. Conclusions: Gal-1 and Gal-3 H-score per bladder did not independently predict for RFS or OS. Intra-tumoral Gal-1/Gal-3 heterogeneity complicates the use of Gal-1 and Gal-3 expression as a prognostic biomarker. Future studies should consider the evaluation of serum and urinary galectins as an approach to mitigate tumor heterogeneity. Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-22-494/coif). EFB reports honorarium fees from Exelixis and AstraZeneca, consulting relationship with Johnson and Johnson, and grants from Pfizer and Astellas, and owns stock in Exelixis, Becton Dickinson, Calithera Biosciences, Medtronic, Macrogenics, Arvinas, Autolus. The other authors have no conflicts of interest to declare. (2023 Translational Andrology and Urology. All rights reserved.)
Databáze:	MEDLINE
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