Squamous Cell/Adenosquamous Carcinomas and Adenocarcinomas of the Gallbladder: An Immunohistochemistry Study of Prognostic Markers

Abstract

Gallbladder cancers (GBCs) are highly aggressive and lethal diseases. However, the key molecular mechanisms responsible for the progression and prognosis of GBCs have not been identified. No biological markers for effectively identifying GBC subtypes have been reported. In this study the expression of keratin 19 (KRT19) and human achaete-scute homolog 1 (hASH1) proteins in 46 squamous cell/adenosquamous carcinomas (SC/ASC) and 80 adenocarcinomas (AC) were examined using immunohistochemistry. Negative KRT19 or positive hASH1 expression were significantly associated with lymph node metastasis, invasion and TNM stage of SC/ASC patients. In contrast, positive KRT19 and hASH1 expression were significantly associated with large tumor size, lymph metastasis, invasion, and TNM stage in AC patients. Univariate Kaplan-Meier analysis showed that loss of KRT19 or elevated hASH1 expression significantly correlated with decreased survival in SC/ASC patients. In contrast, positive KRT19 and hASH1 expression correlated with a shorter survival time in AC patients. Multivariate Cox regression analysis showed that negative KRT19 expression or positive hASH1 expression was an independent poor-prognostic predictor in SC/ASC, but positive KRT19 and hASH1 expression were poor-prognostic factors in AC patients. Our study suggested that hASH1 can be used to determine the malignancy of SC/ASC and AC tumors and is associated with poor prognosis. In contrast, KRT19 is a protective factor in AC patients but a sign of malignancy in SC/ASC patients.