The clinicopathological and prognostic significance of MUC-1 expression in Japanese gastric carcinomas: an immunohistochemical study of tissue microarrays.
BACKGROUND
MUC-1 is synthesized as a single polypeptide that then undergoes proteolytic cleavage, and is associated with the epidermal growth factor receptor tyrosine kinases. In malignancies, MUC-1 may function as an anti-adhesion molecule, but can also promote adhesion and presumably metastasis.


METHODS
Expression of MUC-1, -2, -4 and -5AC was evaluated on tissue microarrays of gastric carcinomas (n = 237) and adjacent non-cancerous mucosa specimens (n = 89) by immunohistochemistry and compared with clinicopathological parameters and survival time of the patients.


RESULTS
MUC-1 was found to be highly expressed in gastric carcinomas in comparison with noncancerous mucosa (p < 0.05) and positively correlated with depth of invasion, lymphatic and venous invasion, lymph node metastasis, UICC staging and MUC-4 expression (p < 0.05), but not with age, tumor size, MUC-2 or MUC-5AC expression (p > 0.05). Intestinal-type carcinomas showed more MUC-1 expression than their diffuse-type counterparts (p < 0.05). Kaplan-Meier analysis indicated that the cumulative survival rate of patients with no MUC-1 expression was significantly higher than those with weak, moderate or strong expression in gastric carcinomas (p < 0.05), but no difference was observed when tumors were stratified according to the depth of invasion (p > 0.05). Cox's analysis showed three independent prognostic factors, depth of invasion, lymphatic invasion and venous invasion, to affect the relationship between MUC-1 expression and prognosis.


CONCLUSIONS
Up-regulation of MUC-1 expression may be involved in pathogenesis, invasion, metastasis and differentiation of gastric carcinoma. Altered expression might therefore be employed as an indicator of pathobiological behavior of gastric carcinoma. MUC-1 expression was found to be a prognostic factor for gastric carcinoma patients, albeit not independent of parameters of invasion.
Li
Xiao-Han
XH
Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Sugitani 2630, Toyama, Japan.
Zheng
Hua-Chuan
HC
Wang
Zhi-Gang
ZG
Takahashi
Hiroyuki
H
Yang
Xiang-Hong
XH
Guan
Yi-Fu
YF
Takano
Yasuo
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D008297:Male; D008875:Middle Aged; D018396:Mucin-1; D009077:Mucins / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D011379:Prognosis; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D046888:Tissue Array Analysis
C520326:MUC-1 protein, human (950-958); D018396:Mucin-1; D009077:Mucins; D010446:Peptide Fragments