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. 2012 Aug;4(2):311-316.
doi: 10.3892/etm.2012.598. Epub 2012 Jun 1.

Prognostic significance of membrane-associated mucins 1 and 4 in gastric adenocarcinoma

Ilseon Hwang  1 , Yu Na Kang, Jin Young Kim, Young Rok DO, Hong Suk Song, Keon Uk Park
Affiliations

Prognostic significance of membrane-associated mucins 1 and 4 in gastric adenocarcinoma

Ilseon Hwang et al. Exp Ther Med. 2012 Aug.

Abstract

Aberrant expression of mucins is likely associated with cancer biology as alterations in the expression and/or glycosylation patterns of various mucins have been noted. Expression of the mucin family in gastric cancers has been reported in numerous studies, but the results are conflicting. Therefore, we investigated the potential use of mucin (MUC)1 and 4 as prognostic markers in gastric cancer according to histological subtype. Three-hundred and sixty-five gastric adenocarcinoma patients who underwent surgical resection were selected for this study. Among the 365 gastric cancer samples tested here, 34% consisted of early gastric cancer and 66% were advanced. In terms of location, 68.7% of the cohort had intestinal-type cancer and 30.7% had diffuse-type. We constructed tissue microarrays with formalin-fixed paraffin-embedded blocks of gastric cancer and these micro-arrays were evaluated for phenotypic expression of MUC1/4 using monoclonal antibodies. Two-hundred and ninety-two patients (92.7%) were positive for MUC1 and 216 (60.5%) were positive for MUC4. MUC1 expression was not correlated with any other clinicopathological variables such as age, gender, depth of invasion, lymph node metastasis, Lauren classification or recurrence. However, loss of MUC4 expression was significantly correlated with recurrence (p=0.033). MUC4 expression was also significantly correlated with better disease-free survival (p=0.049) and particularly in the intestinal-type (p=0.018). Our present findings demonstrated that loss of MUC4 expression can be used as a prognostic marker in gastric cancer. Loss of MUC4 expression is a prognostic indicator of increased recurrence and poor disease-free survival in patients with gastric cancer.

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Figures

Figure 1.
Figure 1.
The majority of the gastric adenocarcinoma cases (92.7%) showed MUC1 expression (A) while others exhibited no MUC1 expression (B).
Figure 2.
Figure 2.
Some tumors of intestinal type were positive for MUC4 (A) while other tumors of intestinal type were negative for MUC4 (C). There was no morphological difference in MUC4-positive and MUC4-negative tumor cells of the intestinal type. Likewise in the diffuse type, some of the tumors were positive (B) while others were negative (D). Morphological differences in MUC4-positive and -negative tumor cells were not noted.
Figure 3.
Figure 3.
Disease-free and overall survival of patients with MUC4 expression and clinicopathological variables in gastric adenocarcinoma. (A) MUC4 expression was significantly correlated with better disease-free survival (p=0.049), while (B) MUC4 expression was not significantly correlated with overall survival (p=0.671). (C) MUC4 expression in intestinal-type or (D) in the older age group was significantly correlated with disease-free survival (p=0.018 and 0.025).
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