Background : This study aims to propose a classification for histological subtyping of AoV cancer based on only immunohistochemical (IHC) staining, excluding relatively subjective morphological features, and its prognostic significance.

Methods : 75 AoV cancers were analyzed CK7, CK20, and CDX2 expression using IHC staining. Based on IHC results, we differentiated subtypes (INT, intestinal; PB, pancreatobiliary; MIX, mixed; NOS, not otherwise specified) using 3 classification criteria and examined their associations with clinicopathological factors.

Results : Classification I, II and III differentiated subtypes; INT (7, 10 and 10 cases, respectively), PB (43, 38 and 37 cases, respectively), MIX (13, 18, and 19 cases, respectively), and NOS subtype (12, 9, and 9 cases, respectively). Significant differences of disease-free survival among subtypes were observed in classifications II and III using CDX2, with the INT subtype exhibiting the longest survival (P=0.032 and P=0.039, respectively). In classification II, the PB and NOS subtypes had higher recurrence risks (HR = 7.749 and 8.965, respectively) compared to INT subtype. The association of advanced T/N stage, poor differentiation, and lymphovascular invasion (LVI) with recurrence risk was also revealed. But multivariate analysis didn't confirm their prognostic significance. In classification II, subtypes differed significantly in T/N stage and LVI. PB subtype patients showed advanced T and N stages and a higher LVI incidence.

Conclusions : The classifications using CDX2 revealed distinct subtypes with prognostic significance. Therefore, the combination of CK7 and CDX2 or the addition of CDX2 to CK7/CK20 can be useful for distinguishing subtypes, predicting disease outcomes and further impacting clinical management of AoV cancer patients.