Clinicopathological significance of loss of heterozygosity in intestinal- and solid-type gastric carcinomas: a comprehensive study using the crypt isolation technique

Abstract

The clinicopathological significance of loss of heterozygosity (LOH) in gastric carcinoma remains poorly understood. We and other researchers have previously demonstrated that LOH is fairly common in intestinaland solid-type gastric carcinomas, but rare in diffuse-type tumors. In this study, we investigated the relationship between clinicopathological variables and LOH status in intestinal-and solid-type gastric carcinomas. The crypt isolation technique was utilized to analyze LOH at 1p36, 3p14, 4p15, 5q21-22, 8p11-12, 9p21, 13q22, 17p13.1 18q21 and 22q13.31 in 113 intestinal-and solid-type gastric carcinomas using a polymerase chain reaction assay. Immunostaining with D2-40 and Elastica van Gieson staining were used to detect lymphatic invasion and vessel invasion, respectively. High LOH rates (49-71%) were observed in all chromosomal regions tested. 1p36 loss was significantly associated with advanced tumors and lymph node metastasis. 8p11-12 loss was significantly associated with lymph node metastasis, lymphatic invasion, and vessel invasion. 17p13.1 (TP53) loss was significantly associated with vessel invasion. 22q13.31 loss was significantly associated with advanced tumors, lymph node metastasis, lymphatic invasion, vessel invasion and late TNM stage. No significant associations were observed between LOH at other chromosomal regions and aggressive behaviors. In addition, significantly higher LOH rates at 1p36, 9p21, 18q21 and 22q13.31 were observed in cardiac tumors compared with noncardiac tumors. These results suggest that in intestinal-and solid-type gastric carcinomas, LOH on 3p14, 4p15, 5q21-22, 9p21, 13q22 and 18q21 is associated with carcinogenesis, while LOH on 1p36, 8p11-12, 17p31.1 and 22q13.31 is associated with tumor progression.

miR-204 targets Bcl-2 expression and enhances responsiveness of gastric cancer

“…13 The latter resides in the long arm of chromosome 9 that is frequently deleted in human cancers. 14, 15, 16 This prompted us to investigate whether the deletion of that region caused miR-204 downregulation in gastric tumoral tissues. To this end, we evaluated the presence of TRPM3 gene loss using a PCR-based test termed Multiplex Ligation-dependent Probe Amplification.…”

APC gene deletions in gastric adenocarcinomas in a Chinese population: a correlation with tumour progression

“…are frequent in gastric adenocarcinomas [16][17][18][19]. Some further studies have shown that DNA deletions at chromosome position 5q21-22 are common in GCs [12,20,21], which is also the chromosome locus of APC. Inactivation of APC in GCs might be also attributed to CNV of the gene.…”

“…Appropriate levels of wild-type APC are critical to cytoskeletal integrity [1,6], cellular adhesion [7] and Wingless/Wnt signalling [5,8,9]. Somatic mutations of APC are common in gastrointestinal cancers [10][11][12]. Truncation of APC results in the disruption of complex formation and ultimately increased cytoplasmic levels of ß-catenin, which up-regulates TCFresponsive genes critical for the proliferation and transformation of epithelial cells of the gastrointestinal tract [13,14].…”

Solid‐type poorly differentiated adenocarcinoma of the stomach: Deficiency of mismatch repair and SWI/SNF complex

“…Solid‐type PDA seems to correspond to solid carcinoma, which is a poorly differentiated variant of tubular adenocarcinoma in the WHO classification . Solid carcinoma is similar to intestinal‐type GC in molecular features . Nonsolid‐type PDA and signet‐ring cell carcinoma correspond to diffuse‐type GC in Lauren’s classification or poorly cohesive carcinoma in the WHO classification…”

“…38 Solid carcinoma is similar to intestinal-type GC in molecular features. 39 Nonsolid-type PDA and signet-ring cell carcinoma correspond to diffuse-type GC in Lauren's classification 40 or poorly cohesive carcinoma in the WHO classification. 38 According to The Cancer Genome Atlas, diffuse-type morphology is associated with GS, which is one of the molecular subtypes of GC.…”