Discrete Immunohistochemical and Clinicopathological Features of Serrated Adenocarcinoma between the Proximal and...

Colorectal serrated adenocarcinoma (SAC), a subtype of colorectal adenocarcinoma determined histologically, has characteristics of epithelial serrations. Here, we examined the immunohistochemical and clinicopathological characteristics of colorectal SAC.

Thirty-three specimens, pathologically diagnosed as SAC in our hospital between 2013 and 2022, were collected for immunohistochemistry of MLH1/MUC2/MUC5AC/p53 and sequencing of BRAF/KRAS mutations.

The proximal colon contained 25 lesions and the distal colon had 8. Patients with proximal SACs were predominantly female, whereas those exhibiting distal SACs were predominantly male (p = 0.003). Overall, lymph node and distant metastasis were present in 17 (52%) and 11 (33%) cases, respectively, with no significant differences between the proximal and distal groups. MLH1 expression loss was more frequent in proximal cases (40%) than distal SACs (13%). Most cases (97%) were MUC2+. MUC5AC+ was significantly more frequent in proximal cases (92%) than distal SACs (37%, p = 0.004). Significantly less p53 overexpression was present in proximal cases (40%) vs. distal SACs (75%). Genetically, the 12 cases of SAC harboring BRAF mutations were all located in the proximal colon, with a significantly greater frequency (p = 0.030), whereas more frequent KRAS mutations were noted in distal SACs. Throughout 5 years of follow-up, 3 patients (2 proximal SAC cases; 1 distal SAC case) died (mean 6.7 months after surgery) because of their disease.

Proximal SACs exhibit distinct clinicopathological and molecular features compared to distal SACs, largely aligning with the sessile serrated and traditional serrated pathways, respectively.