Mucin Expression in Gastric Cancer: Reappraisal of Its Clinicopathologic and Prognostic Significance

Abstract

Context.-The clinical validity of mucin expression in gastric cancer is debated. Whereas several reports demonstrate a correlation between mucin expression and prognosis, others deny such an association.Objective.-This survival analysis study aims to elucidate the prognostic significance of mucin expression in gastric cancer.Design.-A retrospective survival analysis was done with 412 cases of gastric cancer characterized on the basis of MUC immunohistochemistry using MUC2, MUC5AC, MUC6, and CD10 antibodies; the cases were divided into those with a gastric, an intestinal, or a null mucin phenotype based on the predominant mucin.Results.-There was no association between mucin expression and survival when considering overall gastric cancers or the advanced gastric cancer subtype. However, early gastric cancers with a gastric mucin phenotype showed longer survival than those with an intestinal mucin phenotype (P ¼ .01) or a null phenotype (P ¼ .01). In particular, MUC5AC-positive early gastric cancers resulted in longer survival than did those that did not express MUC5AC (P ¼ .009). The loss of MUC5AC expression was identified as an independent, poor prognostic factor in early gastric cancers using the Cox regression proportional hazard model (hazard ratio, 3.50; P ¼ .045).Conclusions.-MUC5AC expression is significantly associated with patient survival and can be used to predict outcomes in the gastric cancers, especially in the early gastric cancers.

Expression of immunohistochemical markers according to histological type in patients with early gastric cancer

“…Furthermore, we also performed IHC staining and extensively examined E-cadherin, b-catenin, VEGF, p53, and Ki-67 expression levels. Although previous studies have not shown consistent results in respect to mucin phenotype expression and its relationship with the histological type of gastric cancer, the available data suggest that mucin phenotype is related to invasiveness, recurrence, and prognosis [2,11,17,21,22]. Our phenotyping data suggested that TAC was associated with intestinal metaplasia [11], but that PCC was derived from gastric mucosa de novo [23].…”

“…The pathobiological characteristics of early gastric cancer (EGC), such as mucin phenotype and the expression of E-cadherin, b-catenin, and vascular endothelial growth factor (VEGF), are associated with the invasiveness, recurrence, and prognosis of the disease [2,[8][9][10][11].…”

Heterogeneity in Gastric Cancer: From Pure Morphology to Molecular Classifications

“…Several authors have found differential genetic and epigenetic alterations in gastric versus intestinal phenotypes [50,51], although the association with specific clinicopathological features and the prognosis is still conflicting [45,51]. During GC progression, a phenotypic switch may occur from gastric to intestinal differentiation [45]; moreover, some authors hypothesise that GC with a gastric phenotype may also progress to poorly differentiated GC [44,47].…”

Histologic purity of signet ring cell carcinoma is a favorable risk factor for lymph node metastasis in poorly cohesive, submucosa-invasive early gastric carcinoma

“…Mucin 5AC and mucin 6 were used as markers of the gastric foveolar and antral phenotype respectively [20,21]. Mucin 2 and CDX2 were used as markers of intestinal differentiation [20,21].…”

“…Mucin 5AC and mucin 6 were used as markers of the gastric foveolar and antral phenotype respectively [20,21]. Mucin 2 and CDX2 were used as markers of intestinal differentiation [20,21]. IHC was performed with a Ventana XT automated stainer (Ventana, Tucson, AZ, USA) with use of antibodies for mucin 5AC (1:2000, clone CLH5; Novocastra, UK), mucin 6 (1:200, clone CCP58, Novocastra), mucin 2 (1:200, clone CLH2, Novocastra), and CDX2 (1:50, clone EPR2764Y, Cell Marque, Rocklin, CA, USA).…”