Poorly differentiated adenocarcinoma of the colon: subsite location and clinicopathologic features.

Purpose: Colorectal cancers of the proximal colon are characterized by good prognosis, microsatellite instability (MSI), and poor differentiation. MSI is associated with a favorable prognosis, but poorly differentiated adenocarcinomas (PDAs) have a poor prognosis. In this study, we aimed to investigate this inconsistency by analyzing the heterogeneity of PDAs.

Methods: A total of 156 surgically resected PDAs were analyzed according to tumor subsite by morphological and immunohistochemical analyses.

Results: Proximal PDAs (n = 86) were significantly associated with females, older age, cytokeratin (CK) 20 downregulation, aberrant MUC5AC expression, and MSI compared with distal PDAs (n = 70). Proximal PDAs tended to show a better overall survival rate than distal PDAs. PDAs with microsatellite stability (MSS) were suggested to progress from well- and moderately differentiated adenocarcinomas (WMDAs), but MSI PDAs typically not. MSI PDAs demonstrated a prognosis marginally better than MSS PDAs, but significantly worse than WMDAs (n = 170). Proximal MSS PDAs had a similar unfavorable prognosis but were significantly associated with females and aberrant MUC5AC expression compared with distal MSS PDAs. MSI may be predictive of prognosis only in proximal PDAs, because nearly all distal PDAs were MSS. In contrast, CK20 downregulation was significantly associated with better prognosis in both subsites.

Conclusions: Proximal PDAs had a better prognosis than distal PDAs due to a higher incidence of MSI PDAs, whose prognosis was significantly worse than WMDAs. Female and MUC5AC expression were characteristic of proximal PDAs independent of MSI. Subsite-specific features of PDAs may serve for subclassification and predicting prognosis.