Prognostic Significance of Cyclin D1 Expression in Small Intestinal Adenocarcinoma

SIMPLE SUMMARY: Small intestinal adenocarcinoma (SIAC) is a rare tumor, with a rising incidence in recent decades. Although the National Comprehensive Cancer Network (NCCN) established the treatment guidelines for SIAC in 2020, there continues to be urgency to search for reliable prognostic factors and therapeutic regimens. Cyclin D1, a critical cyclin-dependent kinase (CDK) 4/6-dependent regulator of G1/S transition, has attracted much interest as a therapeutic target. The cyclin D1 expression in SIACs has not yet been comprehensively studied, owing to the rarity of this tumor. We investigated the clinicopathological and prognostic significance of the cyclin D1 expression in 232 primary SIACs through a multi-institutional study. Cyclin D1 was commonly overexpressed in SIACs, and a high expression of cyclin D1 was identified as a favorable prognostic indicator in SIAC patients. These findings in SIACs may be important to further the understanding of the mechanism of cyclin D1 in carcinogenesis and for applying appropriate patient therapies. ABSTRACT: Cyclin D1, a critical cyclin-dependent kinase (CDK) 4/6-dependent regulator of G1/S transition, has attracted much interest as a therapeutic target. The cyclin D1 expression in small intestinal adenocarcinomas (SIACs) has not yet been comprehensively studied, owing to the rarity of this tumor. We investigated the clinicopathological and prognostic significance of the cyclin D1 expression in 232 surgically resected primary SIACs through a multi-institutional study. A high expression of cyclin D1 (cyclin D1(High)) was detected in 145 SIAC cases (63%), which was significantly higher than that in normal small intestinal mucosa (11%). Cyclin D1(High) was more commonly found in SIACs with a lower T-category and disease stage and KRAS mutation and predicted better patient survival. Multivariate analysis revealed that cyclin D1(High), the absence of retroperitoneal seeding and lymphovascular invasion, and the lower N-category were identified as independent prognostic indicators for patients with SIACs. Specifically, cyclin D1(High) affected patient survival in the lower stage group (stages I and II). In conclusion, cyclin D1 was commonly overexpressed in SIACs, and cyclin D1(High) acted as a favorable prognostic indicator in patients with SIACs. These findings in SIACs may, thus, be important to further comprehend the mechanism of cyclin D1 in carcinogenesis and to strategize appropriate patient therapies.