MUC6 down-regulation correlates with gastric carcinoma progression and a poor prognosis: an immunohistochemical study with tissue microarrays.
OBJECTIVE
MUC6 was first discovered by screening a gastric mucosa cDNA library and is expressed in the mucous cells of the neck zone and antral glands of the stomach. The aim of the present study was to clarify whether down-regulation has any clinicopathological or prognostic significance in gastric neoplasia.


METHODS
Expression of MUC6, MUC5AC and MUC2 was examined using tissue microarrays for immunohistochemistry in gastric carcinomas (n = 225), adenomas (n = 40), and normal mucosa (n = 89) and compared with clinicopathological parameters and survival data.


RESULTS
MUC6 expression was lower in gastric carcinomas than in adenomas or normal mucosa (P < 0.05) and inversely correlated with tumor size, depth of invasion, lymphatic and venous invasion, lymph node metastasis and UICC staging (P < 0.05). Positive links with expression of MUC2 and MUC5AC were noted (P < 0.05). MUC6 expression was lower in diffuse-type than intestinal-type lesions (P < 0.05). Kaplan-Meier analysis indicated that cumulative survival of patients with no MUC6 expression was significantly lower than with weak, moderate or strong expression in all and even advanced gastric carcinoma (P < 0.05). Multivariate analysis showed three independent prognostic factors, depth of invasion, lymphatic and venous invasion, to concordantly affect the relationship between MUC6 expression and prognosis.


CONCLUSIONS
Down-regulation of MUC6 may contribute to malignant transformation of gastric epithelial cells and underlie the molecular bases of growth, invasion, metastasis and differentiation of gastric carcinoma. Altered expression might therefore be employed as an indicator of pathobiological behaviors and prognosis of gastric carcinoma.
Zheng
Huachuan
H
Department of Diagnostic Pathology, School of Medicine, University of Toyama, Sugitani, 2630, Toyama, Japan.
Takahashi
Hiroyuki
H
Nakajima
Takahiko
T
Murai
Yoshihiro
Y
Cui
Zhengguo
Z
Nomoto
Kazuhiro
K
Tsuneyama
Koichi
K
Takano
Yasuo
Y
D000236:Adenoma / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D005500:Follow-Up Studies; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D055272:Mucin-6; D009077:Mucins / Q000096:biosynthesis / Q000378:metabolism*; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D012680:Sensitivity and Specificity; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate; D046888:Tissue Array Analysis / Q000379:methods*
C524734:MUC6 protein, human; D055272:Mucin-6; D009077:Mucins