B7-H3 expression by immunohistochemistry as a negative prognostic biomarker in colorectal carcinoma (CRC) in a racially diverse population.

Abstract

e15127 Background: In CRC, utility of immunotherapy (IT) remains limited to persons with microsatellite instability–high (MSI-H) status. Immunotyping of CRC patients is critical towards further establishing IT's potential. Both incidence and survival rates for CRC in the United States vary between races due to multiple factors including genetic heterogeneity. In this study, we have profiled tumor samples in a racially diverse population for the expression of four different members of the B7 family of immune check point regulators. Methods: Tissue microarray (TMA) was generated from 208 CRC patients. Formalin fixed paraffin embedded (FFPE) tissues were utilized for immunohistochemistry (IHC) post- antigen retrieval. Antibodies specific for IHC staining were used for B7-H3 (D9M2L), PD-L1(E1L3N), B7-H4/B7x(D1M81) and HHLA2(566.1). Each specimen was scored for percent staining of tumor tissue (4 quartile groups) and for intensity (1-4x), and then an overall score (1-16) was calculated. The clinical outcome of interest was overall survival (OS), measured as time from diagnosis of metastatic cancer to death. Analysis for differences in OS was by log rank test, while differences between mean staining was by t test. Race was designated as non-Hispanic white (NHW, n = 41), non-Hispanic black (NHB, n = 84), Hispanic (n = 75), and others (8). Results: B7-H3 protein expression showed strong cytoplasmic distribution. NHB patients had a mean lower expression than NHW patients (0.19 vs 0.41, p = 0.02). Correspondingly, NHB patients had a worse OS than NHW patients (606 vs 759 days). No discernible differences were found in Hispanic patients. PD-L1 showed membranous distribution with 17% expression without significant difference among patients of different racial origin. HHLA2 was more widely expressed with about 35% staining but without statistical significance. B7-H4/B7x failed to show any expression. Conclusions: Expression of B7H3 varies among patients with differential racial backgrounds. It has the potential to be a prognostic biomarker and may be a reason for worse outcome among NHB patients in our population. Other B7 immune checkpoint markers failed to show clinical relevance.