胃癌ER基因表达与CpG岛甲基化的意义

Expression and Methylation of CpG Island of ER Genein Gastric Carcinoma

目的:研究雌激素受体(ER)基因表达及其CpG岛甲基化状况与胃癌生物学行为和预后的关系。方法:分别应用免疫组化SP法和限制性内切酶PCR法分析91例胃癌ER的表达和30例胃癌ER基因CpG岛的甲基化状况。结果:胃癌ER阳性率为38%(35/91),其中高分化腺癌10%(3/30),分别与低分化腺癌43%(13/30),未分化癌53%(8/15),粘液癌63%(5/8)及印戒细胞癌75%(6/8)比较,皆具有显著性差异(P<0.05)。BorrmannⅢ+Ⅳ型56%(24/43)明显高于Ⅰ型22%(4/18)与Ⅱ型23%(7/30)(P<0.05)。淋巴结转移组为55%(28/51),未转移组23%(9/40),两组间有显著性差异(P<0.05)。正常胃粘膜ER基因CpG岛未见甲基化,而40%(12/30)胃癌呈甲基化(P<0.05),且与其蛋白表达有负相关性(P<0.05)。结论:ER在胃癌中的表达与分化、侵袭、转移有关,并以分化较差的胃癌表达高,提示ER阳性胃癌生物学行为差而预后不佳。ER基因CpG岛甲基化可能是胃癌中ER表达缺失的分子机制。

Objective: To investigate the expression of estrogen receptor(ER) and methylation of ER gene CpG island and their correlation with biological behavior and prognosis in gastric carcinoma. Methods: Expression of ER and methylation of ER gene CpG island in exon 1 in gastric carcinoma were examined by streptavidin-peroxidase conjugated method (S-P) and restriction endonuclease-polymerase chain reaction(PCR) analysis respectively. Results: Expression of ER was found in 38% (35/91) of gastric carcinoma. The frequency of ER positivity in well-differentiated(10%, 3/30) was significantly lower than that in pooly-differentiated(43%, 13/30), undifferentiated(53%,8/15), mucoid carcinoma (63%, 5/8) and signet ring cell carcinoma (75%, 6/8)(P<0.05). The positive rate of ER expression in Borrmann type Ⅲ+Ⅳ(56%, 24/43) was higher than that in Borrmann typeⅠ(22%, 4/18) or Ⅱ(23%, 7/30)(P<0.05). There was obvious difference of exprission between lymph node metastases (55%, 28/51) and non-lymph node metastases (23%, 9/40) (P<0.05) . The aberrant methylation of ER gene CpG island in exon 1 was found and there was negative correlation with ER expression (P<0.05). Conclusions: Expression of ER is related to differentiation, invasion and metastasis in gastric carcinoma, and exihibits malignant biologic behaviour and poor biological behaviour prognosis. Methylation of ER gene CpG island is a possible molecular mechanism for loss of ER expression.