ABSTRACT
The clinicopathological characteristics of squamous cell/adenosquamous carcinoma (SC/ASC) of the gallbladder have not been well documented, and no prognosis marker has been identified because of the rare occurrence of this gallbladder cancer subtype. In this study, we examined ACE2 and FZD1 expression in 46 SC/ASCs and 80 adenocarcinomas using immunohistochemistry and further analyzed their correlations with clinicopathological characteristics. We demonstrated that positive FZD1 and negative ACE2 expression were significantly associated with large tumor size, high TNM stage, lymph node metastasis and invasion of SC/ASC and AC. Univariate Kaplan-Meier analysis showed that positive FZD1 and negative ACE2 expression as well as differentiation, tumor size, TNM stage, lymph node metastasis, invasion, and surgical curability were closely associated with decreased overall survival in both SC/ASC (p < 0.001) and AC (p < 0.001) patients. The average survival time in SC/ASC and AC patients with FZD1(-)ACE2(+) expression was significantly longer than that in patients with FZD1(+)ACE2(-) or FZD1(+)ACE2(+) (p < 0.01). Multivariate Cox regression analysis showed that positive FZD1 and negative ACE2 expression are independent poor-prognostic factors for both SC/ASC and AC patients. In addition, FZD1 expression positively, but ACE2 expression negatively correlated with the expression of CA19-9 in SC/ASC and AC. Our study suggested that positive FZD1 and negative ACE2 expression are closely related to the expression of CA19-9; clinical, pathological, and biological behaviors; as well as poor-prognosis of gallbladder cancer.
Subject(s)
Adenocarcinoma/metabolism , Carcinoma, Squamous Cell/metabolism , Frizzled Receptors/metabolism , Gallbladder Neoplasms/metabolism , Peptidyl-Dipeptidase A/metabolism , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma/therapy , Adult , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2 , Biomarkers, Tumor , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Female , Gallbladder Neoplasms/mortality , Gallbladder Neoplasms/pathology , Gallbladder Neoplasms/therapy , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Staging , Prognosis , Tumor BurdenABSTRACT
Although the incidence of gallbladder cancers is low, they are highly aggressive tumors. Squamous cell/adenosquamous carcinoma (SC/ASC) is a rare subtype of gallbladder cancer. The clinical characteristics of SC/ASC have not been well documented, and no prognosis marker has been identified. In this study, we examined integrin-linked kinase (ILK) and peroxiredoxin-1 (PRDX1) expression in 46 SC/ASCs and 80 adenocarcinomas (ACs) by using immunohistochemistry and analyzed their correlations with clinicopathological characteristics. We demonstrated that positive ILK and PRDX1 expressions were significantly associated with large tumor size, high TNM stage, lymph node metastasis, and invasion of SC/ASC and AC. Univariate Kaplan-Meier analysis showed that positive ILK and PRDX1 expressions were closely associated with decreased overall survival in both SC/ASC (p < 0.001 and p = 0.005, respectively) and AC (p < 0.001) patients. Multivariate Cox regression analysis showed that positive ILK and PRDX1 expressions were an independent poor prognostic predictor in both SC/ASC and AC patients. We also revealed a similar significance of differentiation, tumor size, TNM stage, lymph node metastasis, invasion, and surgical curability with survival in SC/ASC and AC patients. Our study suggested that positive ILK and PRDX1 expressions are closely related to the progression and poor prognosis of gallbladder cancer.
