Mcl-1 Expression May Be Associated With Favorable Clinical Outcome in BRAF V600E–Mutated MMR-Deficient Colorectal Cancers

Objectives The BRAF V600E mutation is associated with treatment resistance and is a poor prognostic indicator in colorectal adenocarcinomas (CRAs). Prior studies have shown that the BRAF V600E mutation confers resistance to apoptosis by Mcl-1 gene upregulation. We evaluated the clinical effect of Mcl-1 expression on BRAF-mutated (BM) MMR-deficient (dMMR) CRAs. Methods Thirty-one BM dMMR CRAs were included in a tissue microarray. The intensity and extent of Mcl-1 expression were evaluated by immunohistochemistry. Staining intensity (0-3+) and percentage of cells with positive staining (none, <10% = 1, 10%-50% = 2, and >50% = 3) were determined. Cases were considered positive when the intensity score multiplied by the percentage category score was >4. Mcl-1 expression was correlated with clinicopathologic features. Results Positive Mcl-1 staining was identified in 13 (42%), among which 9 (69.2%) were well to moderately differentiated with lymphovascular invasion present in 4 (30.8%), lymph nodes metastases in 3 (23.1%), and AJCC stage pT3 or greater in 8 (61.5%). In contrast, 18 (58%) were Mcl-1 negative, among which 10 (55.6%) were poorly differentiated with lymphovascular invasion present in 12 (66.7%), lymph node metastases in 9 (50%), and AJCC stage pT3 or greater in 14 (77.8%). Conclusion Among 31 examined BM dMMR CRAs, cases that demonstrated Mcl-1 expression were associated with a lower grade, lower rate of lymphovascular invasion and lymph node metastasis, and lower AJCC stage. While Mcl-1 expression confers resistance to apoptosis, this study suggests that Mcl-1–positive tumors demonstrate pathologic features associated with a favorable clinical outcome.