Prognostic Value of Retinoblastoma in Small Intestinal Adenocarcinoma: A Multicenter Retrospective Study

The retinoblastoma (RB) protein which is encoded by RB gene selectively provides a cell type-specific function in malignancies. In colorectal carcinoma, RB has been highly expressed and related cyclin/cyclin-dependent kinase 4/6 inhibitors have shown improved therapeutic effects in some patients. However, little is known about RB in small intestinal adenocarcinoma (SIAC).

Here, we conducted a multi-institutional study of RB expression in 229 surgically resected SIACs to explore the clinicopathologic and prognostic implications and the relationship with microsatellite instability (MSI) status and KRAS mutations.

High RB expression (RB^High) was more commonly observed in SIACs (76/229, 33%) than in normal small intestinal mucosa (27/188, 14%; P < 0.001). RB^High was associated with nodular growth patterns (P = 0.028), the absence of lymphovascular (P = 0.001) and perineural invasion (P = 0.048), and a lower T category (P = 0.042) and indicated better overall survival (P = 0.003). In multivariate analysis, RB^High (P = 0.049) was an independent prognostic predictor of better prognosis, along with younger patient age (P = 0.049), the absence of retroperitoneal seeding (P = 0.004), lower tumor stage (P < 0.001), and MSI (P = 0.005). The prognostic impact of RB expression was consistently observed regardless of MSI status and specifically persistent in SIACs with lower stages (stages I and II).

RB^High was related to favorable clinicopathologic SIAC characteristics and indicated better patient prognosis. The prognostic predictability of RB was found in SIACs with lower stages, independent of MSI status. RB expression is a reliable and potent prognostic indicator for SIAC and may aid in selecting chemotherapy for patients.