Abstract 768: Immunohistochemistry analysis of the molecular subtypes of muscle invasive bladder cancer in association with prognosis
Authors: Pham QuocThang , Do Anh Toan , Nguyen Ngoc Minh Tam , Nguyen Phuc Nguyen , Doan Thi Phuong Thao , Bui Thi Thanh Tam , Ngo Quoc Dat 
Published: April 2023

Background: Bladder cancer (BC) is one of the most common cancers worldwide. Muscle invasion BC (MIBC) has a poor prognosis and is usually in an advanced stage. Recently, whole genome sequencing research in BC has pointed out the molecular subtypes of BC which presented correlate with the patient outcome as well as clinical behavior. There are differences between the stratification’s subtypes determined by several research teams. However, the central of these stratifications are classified the BC into the basal BC type and the luminal BC type. We aim to use the immunohistochemical surrogated markers for basal and luminal BC subtypes to discriminate the molecular subtypes of BC and their association with the clinicopathologic features of BC. Method: We performed IHCs for surrogated basal makers (CK5/6 and CD44), and surrogated luminal makers (CK20 and Gata3) in 130 MIBC patients. IHCs classified the MICB into the fourth group including basal type (positive with CK5/6 and/or CD44 and negative both of CK20 and Gata3), luminal type (negative both of CK5/6 and CD44 and positive with CK20 and/or Gata3), null type (negative for all fourth markers) and mixed type (expressed both basal and luminal markers), respectively. We investigated the relationship between the molecular subtypes and the clinicopathological significance of MIBC patients. Furthermore, we analyzed the association of molecular subtypes with the overall survival of MIBC patients. We also analyzed the IMVigor210 cohort and the TCGA-BLCA cohort to validate our results. We investigated the chemo reagents (cisplatin, and 5-Fu) resistance of the BC cell lines which molecular subtypes classified by IHCs. Results: We figured out that the basal subtype and luminal subtype presented 35.28% and 29.23% of MIBC respectively. The null subtype accounted for 18.47% of MIBC. The basal subtype was associated with T stage (p=0.035), squamous differentiation (p=0.0002), stage (p=0.035), and tumor infiltrated lymphocytes (TILs) (p=0.047). There were no significantly different between the overall survival of the basal and mixed subtype of MIBC and the luminal and null subtype MIBC (Log-rank test, p=0.090). Interestingly, we explored that the MIBC without intensive TILs - basal subtype presented the worst prognosis in comparison with other molecular subtypes (Log-rank test, p=0.012). The mRNA basal subtype also presented poor prognosis in BC without immune activities in BLCA (p=0.037) or in IMVigor210 (p=0.0005). Furthermore, the basal cell lines presented lower IC50 than luminal cell lines when treated the cells with cisplatin. Conclusion: Our results pointed out that the molecular subtypes of MIBC were associated with the progression of MIBC. The MIBC patients without intensive TILs - basal subtype have the worst outcome. Suggesting that stratification of molecular subtypes of MIBC by IHCs are appealing option for clinical implementation.

Citation Format: QuocThang Pham, Anh Toan Do, Ngoc Minh Tam Nguyen, Phuc Nguyen Nguyen, Thi Phuong Thao Doan, Thi Thanh Tam Bui, Quoc Dat Ngo. Immunohistochemistry analysis of the molecular subtypes of muscle invasive bladder cancer in association with prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 768.