Discrete immunohistochemical and clinicopathological features of serrated adenocarcinoma between the proximal and distal colon

Introduction: 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. Methods: Thirty-three specimens, pathologically diagnosed as SAC in our hospital between 2013–2022, were collected for immunohistochemistry of MLH1/MUC2/MUC5AC/p53, and sequencing of BRAF/KRAS mutations. Results: 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, three patients (two proximal SAC cases; one distal SAC case) died (mean 6.7 months after surgery) because of their disease. Conclusion: Proximal SACs exhibit distinct clinicopathological and molecular features compared to distal SACs, largely aligning with the sessile serrated and traditional serrated pathways, respectively.