乳腺癌促性腺激素释放激素受体(GnRH-R)的表达及临床意义

The expression of gonadotropin releasing hormone receptor(GnRH-R)in breast cancer and the analysis of its clinical significance

目的探讨促性腺激素释放激素受体(gonadotropin releasing hormone receptor,GnRH-R)在乳腺癌组织中的表达以及与临床病理特征、预后的相关性。方法收集2013年至2018年间诊断的早期浸润性乳腺癌组织656例以及癌旁组织131例,制成组织芯片。应用免疫组化方法检测乳腺癌组织中GnRH-R表达的情况,通过Logistic回归分析GnRH-R高表达相关的临床病理因素,通过Kaplan-Meier法以及Log-Rank检验比较GnRH-R高表达与低表达患者的无病生存期(disease free survival,DFS)。结果乳腺癌癌组织中GnRH-R高表达率显著高于癌旁组织(54.0%vs.28.2%,P<0.001);在雌激素受体(estrogen receptor,ER)阴性乳腺癌中,GnRH-R高表达率显著高于ER阳性乳腺癌(65.3%vs.48.0%,P<0.001)。多因素分析显示,较低的N分期、肺泡淋巴管侵犯(lymphovascular invasion,LVI)阴性以及高Ki-67是GnRH-R高表达的独立相关因素。尽管在整体样本中,GnRH-R高表达与低表达患者的DFS无显著性差异(Log Rank P=0.132),但是在ER阴性乳腺癌中,GnRH-R高表达的患者较低表达的患者DFS显著改善(Log Rank P=0.023)。结论GnRH-R可能是乳腺癌潜在的治疗靶点,尤其是激素受体阴性的乳腺癌。

Objective To evaluate the expression of gonadotropin releasing hormone receptor(GnRH-R)in breast cancer and to analyze its significance with clinical-pathological characteristics and survival outcomes.Methods Tissue microarrays were comprised of 656 cases of early invasive breast cancer tissue diagnosed between 2013 and 2018 together with 131 cases of paracancerous tissue.The expression of GnRH-R was evaluated by immunohistochemistry.The independent related factor with high expression of GnRH-R was evaluated by multiple Logistic regressions.The disease-free survival(DFS)outcomes between patients with high or low expression of GnRH-R were compared by means of KaplanMeier methods and Log-Rank test.Results The high expression rate of GnRH-R was significantly higher in tumor tissue than in paracancerous tissue(54.0%vs.28.2%,P<0.001),and was also significantly higher in estrogen receptor(ER)negative breast cancer than in ER positive breast cancer(65.3%vs.48.0%,P<0.001).According to multiple Logistic regressions,lower N stage,negative lymphovascular invasion(LVI)and higher Ki-67 level were independent related factors with high expression of GnRH-R.Although there was no significant difference in DFS between patients with high and low expression of GnRH-R(Log Rank P=0.132)as a whole,cases with high expression of GnRH-R had significantly improved DFS compared with those with low expression of GnRH-R(Log Rank P=0.023)among ER negative patients.Conclusion GnRH-R might be a potential treating target for breast cancer,especially for hormone receptor negative breast cancer.