Prediction of Prognosis in Gallbladder Carcinoma by Mucin and p53 Immunohistochemistry

Abstract

Mucin core proteins are known to be present in various organs and are specifically expressed with carcinogenesis and closely associated with the prognoses of various malignant tumors in the digestive tract such as colorectal cancer. The present study evaluated correlations between mucin and p53 expression and prognosis of gallbladder cancer using surgically resected tissue specimens from 26 patients with gallbladder carcinoma surgically treated at our hospital. Immunohistochemical staining was performed using MUC 1, MUC2, and p53 monoclonal antibody. The level of antigen expression in the lesion was classified into four stages: none(-), slight(+), moderate (++), and severe (+ + +). According to the UICC classification, histopathological grading, levels of T, N, and M factors, and tumor stages were compared with regard to the correlations with mucin and p53 expression. All cases were classified into two groups according to the results of mucin immunohistochemistry: group A (MUC1, > or = ++; and MUC2, < or = +) and group B (MUC1, < ++; or MUC2, > +). Postoperative survival periods were compared between the two groups and p53-positive and -negative groups. Neither histological grading nor T factor correlated with mucin or p53 expression, respectively. Moreover, neither N factor nor M factor correlated with mucin or p53 expression. Furthermore, stage grouping did not correlate with mucin or p53 expression. However, when the correlation between the postoperative survival period and mucin expression was evaluated, the mean postoperative surgical period was significantly shorter in Group A than in Group B (1.02 years in Group A vs 2.92 years in Group B; P = 0.016). There was no relationship between postoperative survival period and p53 positivity. Mucin expression was independent of various tumor growth factors and clearly reflected the prognosis of gallbladder cancer. Because the relative malignancy of gallbladder cancer could be evaluated by examining the level of glycoprotein expression in tumor tissue, mucin could be a more important marker than p53 for predicting prognosis in gallbladder carcinoma using surgically resected tissue specimens.

Prognostic significance of muc4 expression in gallbladder carcinoma

“…These observations support the theory that MUC1 expression could be particularly prevalent in gallbladder carcinoma, and could contribute to the progression of gallbladder carcinomas. Regarding the prognostic value of MUC1 expression in gallbladder carcinoma, several studies described an association with a poor outcome in univariate analysis [34,35], but this study showed no relation between MUC1 expression and the outcome of patients with gallbladder carcinoma. This difference might be explained by various glycoforms of the MUC1 antigen, including underglycosylated, sialylated, and fully glycosylated forms [6], and these discrepancies in expression rates.…”

“…These results suggest that MUC2 expression is related to noninvasive proliferation of the tumor, resulting in a favorable outcome. But MUC2 expression has not been related to clinical outcome in gallbladder carcinoma [34,35]. This study also found that although MUC2 expression appeared linked to better survival, this was not statistically significant.…”

Adenocarcinoma of the Gallbladder: Biology of Disease, Prognosticators, and Staging

“…On the other hand, other investigations reported a role of p53 gene mutation in the transition from premalignancy to malignancy (Ajiki et al 1996;Moreno et al 2005) and a correlation between p53 expression in CG and poor survival (Takagawa et al 2005). An important regulator of chromatin, involved in silencing tumor suppressor genes, is the histone deacetylase (HDAC) system.…”

Exploring the role and diversity of mucins in health and disease with special insight into non-communicable diseases

“…Rate and pattern of MUC1 protein expression suggest that MUC1 would be a marker of malignant transformation of invasion of gallbladder cancer [365,366]. Prognostic value of mucin (MUC1 and MUC2) in gallbladder carcinoma along with other tumor growth factors (like p53 was carried out but Mucin expression was found to be independent of various tumor growth factors and clearly reflected the prognosis of gallbladder cancer [367].…”