Clonal analysis of superficial depressed-type gastric carcinoma in humans

Abstract

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.

Time-dependent expression of intestinal phenotype in signet ring cell carcinomas of the human stomach

“…Gastric carcinoma is known to have a long natural history. This concept was supported by the recent clonal analysis [1], demonstrating that most of the superficial depressed, diffuse-type gastric carcinomas were of monoclonal constitution. The size of intramucosal lesion is thus considered to reflect the length of the natural history of the tumor from an incipient carcinoma.…”

“…However, this conclusion has to be reconsidered, taking the following aspects into consideration. Signet ring cell carcinoma, even of the superficially spreading type, has recently been demonstrated to be mostly monoclonal; the size of the tumor cell mass is thought to reflect the time the tumor growth takes from the incipient stage [1]. Accordingly, the spreading fronts in the mucosal part of signet ring cell carcinoma are known to show a characteristic layered structure in which proliferating tumor cells are confined to the middle level of the mucosa consistently from the incipient to the advanced stages [6,22].…”

Heterogeneity of p53 mutational status in the superficial spreading type of early gastric carcinoma

“…Bamba et al [23] have reported that most SSEGCs are monoclonal; their methodology included using polymorphisms of the X-linked human androgen receptor gene (HUMARA) methods. They examined eight informative cases, and only one case showed heterogeneity.…”

Destabilized Adhesion in the Gastric Proliferative Zone and c-Src Kinase Activation Mark the Development of Early Diffuse Gastric Cancer

“…Other similarities to eHDGC include the SRCC structure and location, with typical SRCs in the luminal part and the proliferative activity concentrated in small cells close to the neck region (34,35). Our view is in agreement with that of Sugihara et al, who almost 20 years ago proposed that luminal SRCs may be terminally differentiated, and arise from the neck region (35).…”