Combined tumor epithelial and stromal histopathology with keratin 81 expression predicts prognosis for pancreatic ductal adenocarcinoma

Background: Development of a pragmatic pathologic classifier of pancreatic ductal adenocarcinoma (PDAC) that reflects biological behavior is needed. Methods: The tumor epithelial and stromal features of PDAC and molecular subtype-related markers were evaluated in three independent cohorts. Results: In the non-neoadjuvant therapy cohort (n = 108), regarding tumor-epithelial feature, non-gland-forming type showed worse prognosis compared to gland-forming type (P < .001). For tumor-stromal feature, in gland-forming type, the prognosis was good in order of inactivated stroma-rich, stroma-poor, and activated stroma-rich (P = .027). Whereas, non-gland-forming type revealed no difference of prognosis according to tumor stroma. Of molecular subtype-related markers, keratin 81 expression was correlated with non-gland-forming type and poor prognosis (P = .005 and P = .021, respectively). Other markers (HNF1A, c-MET, and p53) showed no significant differences in prognosis. In the neoadjuvant therapy cohort (n = 68), non-gland-forming type was correlated with high residual tumor volume (>= 20%) (P < .001) and gland-forming/stroma-poor type was not present. In the next-generation sequencing cohort (n = 55), non-gland-forming type was correlated with a higher number of the KRAS, TP53, CDKN2A, and SMAD4 mutations (P = .038). Conclusion: Combined tumor epithelial and stromal histopathology with keratin 81 expression is suggested to be useful for predicting prognosis of PDAC.

Automated summary

The study identified factors related to prognosis in pancreatic ductal adenocarcinoma (PDAC), such as keratin 81 expression and stromal features. Combining tumor histopathology with keratin 81 expression may be useful for predicting the prognosis of PDAC.