Clinicopathological significance of loss of heterozygosity in intestinal- and solid-type gastric carcinomas: a comprehensive study using the crypt isolation technique
Clinicopathological significance of loss of heterozygosity in intestinal- and solid-type gastric carcinomas: a comprehensive study using the crypt isolation technique
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DOI：
10.1038/modpathol.3800561
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发表时间：
2006-04-01
期刊：
影响因子：
7.5
通讯作者：
Nakamura, S
中科院分区：
文献类型：
--
作者：
Jiao, YF;Sugai, T;Nakamura, S
胃癌中杂合性缺失（LOH）的临床病理意义尚不清楚。我们和其他研究人员先前已经证明LOH在肠型和固体型胃癌中相当常见，但在弥漫性肿瘤中很少见。在这项研究中，我们研究了肠型和固体型胃癌的临床病理变量与LOH状态的关系。采用隐窝分离技术，采用聚合酶链反应法分析113例肠型和固体型胃癌的1p36、3p14、4p15、5q21-22、8p11-12、9p21、13q22、17p13.1、18q21和22q13.31位点的LOH。D2-40免疫染色和Elastica van Gieson染色分别检测淋巴浸润和血管浸润。在所有检测的染色体区域均观察到高LOH率（49% -71%）。1p36丢失与晚期肿瘤和淋巴结转移显著相关。8p11-12丢失与淋巴结转移、淋巴浸润和血管浸润显著相关。17p13.1 （TP53）缺失与血管侵袭显著相关。22q13.31损失与肿瘤进展、淋巴结转移、淋巴浸润、血管浸润和TNM晚期相关。其他染色体区域的LOH与攻击行为之间无显著关联。此外，心脏肿瘤中1p36、9p21、18q21和22q13.31位点的LOH率明显高于非心脏肿瘤。这些结果表明，在肠型和固体型胃癌中，3p14、4p15、5q21-22、9p21、13q22和18q21上的LOH与癌变有关，而1p36、8p11-12、17p31.1和22q13.31上的LOH与肿瘤进展有关。
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 intestinal- and 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.