Cytoplasmic expression of B7-H3 is associated with higher grade and worse disease-specific survival in patients with clear cell renal cell carcinoma

Introduction: B7 homolog 3 (B7-H3) (CD276) is a member of the B7 family of immune proteins that provide signals for regulating immune responses. Recently, it has been shown that B7-H3 is highly overexpressed on a wide range of human solid cancers and often correlates with both negative prognosis and poor clinical outcome in patients. In this study, for the first time, we have mapped the membranous, cytoplasmic and nuclear expression levels of B7-H3 biomarker in three major subtypes of renal cell carcinoma (RCC), related to disease stage, aggressiveness and patient survival outcomes. The results provide a basis for future diagnosis, prognosis and clinical choice of targeted therapy in RCC and may help to define subgroups of patients requiring different follow-up strategy. Materials and methods: Expression of B7-H3 was evaluated using immunohistochemistry in RCC samples on tissue microarrays including clear cell RCCs (ccRCCs), type I and II papillary (pRCC), and chromophobe RCCs (chRCC). The association between B7-H3 expression and clinicopathological features as well as survival outcomes was determined.Results: There was a statistically significant difference between B7-H3 expression among the different RCC subtypes. In ccRCC, higher cytoplasmic expression of B7-H3 was significantly associated with increase in nucleolar grade (P = 0.045) , lymph node invasion (LNI) (P = 0.037), invasion of the Gerota’s fascia (P = 0.048), and histological tumor necrosis (P = 0.014), while no association was found with the membranous and nuclear expression. In addition, the median expression of B7-H3 was seen more in the high grade of RCC compared with the low grade of RCC. Moreover tumors with cytoplasmic expression of B7-H3 tended to have a worse prognosis for disease-specific survival (DSS) than those with membranous expression (Log-rank test: P = 0.015). In chRCC, we found a significant association between cytoplasmic B7-H3 expression and distant metastasis (P = 0.047) and membranous B7-H3 expression and microvascular invasion (MVI) (P = 0.047), however, we did not observe a significant association between B7-H3 expression and survival data in these cases. Further, we found no significant association between membranous, cytoplasmic, and nuclear B7-H3 expression and important clinicopathological parameters and patients outcomes in type I and II pRCC.Conclusions: Our results demonstrated that higher cytoplasmic B7-H3 expression is associated with more aggressiveness tumor behavior and poor DSS in ccRCC, therefore, evaluation of the pattern of B7H3 expression in cytoplasm is useful for predicting cancer prognostication and therapeutic marker for targeted therapy in ccRCC.

کلیدواژه ها:

B7-H3 ، Renal cell carcinoma (RCC) ، Tissue microarray (TMA)