Phenotypic classification of gastric signet ring cell carcinoma and its relationship with K-ras mutation.
Phenotypic classification of gastric signet ring cell carcinoma and its relationship with K-ras mutation.
复制标题
胃印戒细胞癌的表型分类及其与K-ras突变的关系。
作者：
Z. Xiong;J. Shi;Z. Fu;H. Wan;L. Tu
本研究旨在通过检测胃和肠表型标志物的表达，分析胃印戒细胞癌（SRC）的亚型，并探讨表型与K-ras突变的关系。对163例SRC癌患者标本进行免疫组化，以检测胃（MUC 1、MUC 5AC和MUC 6）和肠（MUC 2和CDX 2）表型标志物，并将肿瘤分为胃（G）、肠（I）和胃肠道（GI）表型。从福尔马林固定、石蜡包埋的肿瘤样本中提取DNA，并使用基于聚合酶链反应的直接DNA测序鉴定密码子12、13和61中的K-ras突变。G、GI和I表型分别为63例（38.6%）、71例（43.5%）和29例（17.8%）。MUC 2的表达与浸润深度和淋巴结转移显著相关（分别为P = 0.001和0.002），而CDX 2的表达与肿瘤大小和粘膜下浸润显著相关（分别为P = 0.004和0.001）。MUC 5AC表达与胃壁浸润呈负相关（P = 0.001）。肠表型标志物表达与胃壁浸润和淋巴结转移呈正相关。20例（12.27%）K-ras基因突变均位于第12位密码子，与I型显著相关，与MUC 5AC和MUC 6表达呈负相关。I-表型SRC癌与G表型SRC癌相区别，因为I-表型SRC癌在侵袭和转移方面恶性程度增加，K-ras畸变率较高。不同的K-ras基因突变频率意味着不同的遗传机制，在癌变的I-和G-表型胃癌SRC。
We aimed to analyze gastric signet ring cell (SRC) carcinoma subtypes by investigating gastric and intestinal phenotypic marker expression, and explore the relationship between phenotype and K-ras mutation. Immunohistochemistry was performed on 163 SRC carcinoma patient specimens to detect gastric (MUC1, MUC5AC, and MUC6) and intestinal (MUC2 and CDX2) phenotypic markers, and tumors were classified into gastric (G), intestinal (I), and gastrointestinal (GI) phenotypes. DNA was extracted from the formalin-fixed, paraffin-embedded tumor samples, and K-ras mutations in codons 12, 13, and 61 were identified using polymerase chain reaction-based direct DNA sequencing. G, GI, and I phenotypes were observed in 63 (38.6%), 71 (43.5%), and 29 cases (17.8%), respectively. Expression of MUC2 was significantly associated with invasion depth and lymph node metastasis (P = 0.001 and 0.002, respectively), whereas that of CDX2 significantly corresponded to tumor size and submucosal invasion (P = 0.004 and 0.001, respectively). MUC5AC expression was inversely associated with gastric wall invasion (P = 0.001). Intestinal phenotypic marker expression was positively associated with gastric wall invasion and lymph node metastasis. K-ras mutations, all of which were in codon 12, were detected in 20 (12.27%) tumors, were significantly associated with the I phenotype, and exhibited an inverse relationship with MUC5AC and MUC6 expression. I-phenotype SRC carcinomas should be distinguished from those of the G phenotype because of their increased malignancy regarding invasion and metastasis, and higher K-ras aberration rate. The different K-ras mutation frequencies observed imply distinct genetic mechanisms in the carcinogenesis of I- and G-phenotype gastric SRC carcinomas.