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Clonal analysis of superficial depressed‐type gastric carcinoma in humans
Author(s) -
Bamba Masamichi,
Sugihara Hiroyuki,
Okada Katsuji,
Bamba Tadao,
Hattori Takanori
Publication year - 1998
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19980901)83:5<867::aid-cncr10>3.0.co;2-t
Subject(s) - histogenesis , locus (genetics) , polymerase chain reaction , monoclonal , pathology , carcinoma , allele , staining , cancer , dna , biology , epithelioma , immunohistochemistry , monoclonal antibody , microbiology and biotechnology , gene , medicine , genetics , antibody
BACKGROUND An important unanswered question concerning the histogenesis of superficial‐type gastric carcinoma is whether it is monoclonal or multiclonal in origin. Therefore, the authors analyzed multiple areas of each cancer with a clonality assay based on trinucleotide repeat length polymorphism of the human androgen receptor gene (HUMARA) that was subject to random inactivation of X chromosomes. METHODS The HUMARA assay was applied to 15 gastric carcinomas, early and advanced stage, manifested in superficial, depressed lesions of various sizes and at least some signet ring cells. DNA was extracted from fresh frozen and formalin fixed tumor tissues that were microdissected from the mucosal lesions, and the HUMARA locus was amplified by polymerase chain reaction with and without prior digestion of nonmethylated DNA with Hpa II. The amplified DNA samples were loaded on polyacrylamide gels, electrophoresed, and visualized by a silver‐staining method. RESULTS In the 15 cases examined, 9 cancers were informative (had features of the types sought in this study), and in these 9 cancers a total of 57 areas were analyzed. In 7 of the 9 cancers, the inactivated allele was common to all the informative areas of each tumor, irrespective of the macroscopic shape of the tumor or the degree of histologic heterogeneity within it. In one of the two remaining cancers, the inactivated allele of one of the areas examined was different from those in the other areas. CONCLUSIONS Most of the superficial depressed‐type gastric carcinomas in this study were demonstrated to be of monoclonal origin. This finding supports a notion expressed previously in the literature that superficial‐type carcinoma has a long natural history, and it indicates that efforts to detect gastric carcinomas in early stages to improve patients' survival should be encouraged. Cancer 1998;83:867‐875. © 1998 American Cancer Society.