CLONAL ANALYSIS OF SUPERFICIAL DEPRESSED-TYPE GASTRIC-CARCINOMA IN HUMANS

BACKGROUND. An important unanswered question concerning the histogenes is of superficial-type gastric carcinoma is whether it is monoclonal o r multiclonal in origin. Therefore, the authors analyzed multiple area s 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 HUMA RA assay was applied to 15 gastric carcinomas, early and advanced stag e, manifested in superficial, depressed lesions of various sizes and a t least some signet ring cells. DNA was extracted from fresh frozen an d formalin fixed tumor tissues that were microdissected from the mucos al lesions, and the HUMARA locus was amplified by polymerase chain rea ction with and without prior digestion of nonmethylated DNA with Hpa I I. The amplified DNA samples were loaded on polyacrylamide gels, elect rophoresed, and visualized by a silver-staining method. RESULTS. In th e 15 cases examined, 9 cancers were informative (had features of the t ypes 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 comm on to all the informative areas of each tumor, irrespective of the mac roscopic 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 ar eas. CONCLUSIONS. Most of the superficial depressed-type gastric carci nomas 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 indicat es that efforts to detect gastric carcinomas in early stages to improv e patients' survival should be encouraged. (C) 1998 American Cancer So ciety.