Molecular pathological analysis of mucinous adenocarcinomas of the stomach.
OBJECTIVE
Mucinous adenocarcinomas (MACs) of the stomach usually show an invasive expansive growth and a poor prognosis. We examined the possibility of molecular pathological subtyping of MACs of the stomach.


METHODS
Forty-one formalin-fixed and paraffin-embedded MAC specimens of the stomach were analyzed. Mucin subtypes (MUC2, CD10, HGM, M-GGMC-1) and expression levels of hMLH1, p53 and Ki-67 were analyzed by immunohistochemistry as well as genetic alterations in the p53 gene and microsatellite instability (MSI).


RESULTS
According to both MSI and p53 status, these tumors were subclassified into three groups: the mutator-type tumors, the suppressor/p53-type tumors and the unclassified tumors. The mutator-type tumors demonstrated lower p53 expression and had lower proliferative activity than the suppressor/p53-type tumors, whereas most of the suppressor/p53-type tumors expressed CD10. However, there was no significant difference between the mutator- and suppressor/p53-type tumors in clinicopathological parameters including the patients' outcome.


CONCLUSIONS
Our results indicate that MACs of the stomach are composed of at least three subtypes according to the molecular pathological background for their carcinogenesis. Further study of carcinomas with detailed morphological and biological phenotyping of each subtype may provide useful information for better clinical management.
Wu
Ming
M
Division of Surgical Pathology, Department of Biomedical Informatics, Kobe University Graduate School of Medicine, Kobe, Japan.
Semba
Shuho
S
Li
Dong
D
Yokozaki
Hiroshi
H
D048868:Adaptor Proteins, Signal Transducing; D002288:Adenocarcinoma, Mucinous / Q000145:classification* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins; D004273:DNA, Neoplasm / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D016158:Genes, p53; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009077:Mucins / Q000145:classification / Q000378:metabolism; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000145:classification* / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; C501486:MLH1 protein, human; D009077:Mucins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D000070957:MutL Protein Homolog 1