FOXM1 and MMR genes immunohistochemical expression in colorectal cancer: promising prognostic insights and candidate therapeutic targets

Abstract

Background and objectives Colorectal cancer (CRC) high mortality in developing countries necessitates the delineation of the underlying mechanisms compromising its prognosis despite of current advances. Mismatch repair (MMR) genes protein expression is established as a surrogate to categorize CRC MMR status with different prognostic and therapeutic considerations, variations are observed not only among different classes but also within the same class. FOXM1 is involved in multitask carcinogenesis and is recently targeted in some cancers. Our objective was to study FOXM1 expression in different CRC subclasses to exploit any potential inferences of its role. Material and methods This retrospective study encompassed 51 CRC specimens received in Ain Shams University Hospital, immunohistochemical studies for microsatellite stability genes to determine MMR status and FOXM1 expression were performed. Results were statistically compared and correlated to the clinicopathological prognostic indices. Results FOXM1 expression was statistically significant when correlated to lymphovascular invasion and nodal metastasis. Despite failing to establish a statistical correlation with FOXM1 expression level yet a suggestive tendency of overexpression with precursor tubulovillous adenoma, mucinous and signet ring CRC, grade 3, PT3 was noted. FOXM1 high expression concorded with MMR deficient status, mounting to a statistical significance in right CRCs, this association was disrupted when nodal status was tested. Conclusion FOXM1 shows varying expression in CRC subclasses, variations did not follow a consistent synergistic pattern thus the effect of FOXM1 on prognostic indicators likely involves molecular coded cross-talks with mismatch repair genes as well as others. We offer innovative insights for prognostic aptitudes of FOXM1 that might pave promising utility in future if further validated.