GPR30在卵巢癌的亚细胞定位及临床意义

Cellular Localization and Clinical Relevance of GPR30 in Ovarian Cancer

【目的】研究GPR30在卵巢癌中的亚细胞定位及临床意义。【方法】应用免疫组化技术检测我院2000-2010年的110例卵巢癌组织中GPR30的表达,分析GPR30与卵巢癌的临床病理特点的关系。同时应用流式分选技术和免疫荧光技术检测GPR30在卵巢癌的亚细胞定位。【结果】GPR30在62.7%的卵巢癌组织中表达,其中包括51例浆液性腺癌和4例黏液性腺癌中(P=0.102)。肿瘤残余组(R1,33/45)中GPR30表达率高于无残留组(R0,34/65),具有统计学差异(P=0.030)。在卵巢癌复发组中,73.7%的卵巢癌组织(42/57)可检测到GPR30表达阳性,而GPR30在50.9%的非复发组卵巢癌组织(27/53)中表达阳性(P=0.018)。进展型卵巢癌及低分化卵巢癌中GPR30表达率较早期卵巢癌和高分化卵巢癌中GPR30表达率高,但无统计学差异。5年随访发现,存活的患者中有33例的卵巢癌组织表达GPR30,而GPR30表达于66.7%的死亡病例中,二者无统计学差异。流式分选及免疫荧光技术卵巢癌细胞系SKOV-3细胞内GPR30表达,其中细胞核上GPR30表达明显高于细胞质上GPR30。【结论】GPR30表达阳性的卵巢癌肿瘤残留率、术后复发率增加,不同病理类型、临床病理分期及组织分级的卵巢癌中GPR30表达无明显差异。卵巢癌细胞中GPR30具有核聚集表达现象,从而诱导卵巢癌发生发展的新机制。

[Objective] To demonstrate the cellular localization and clinical relevance of G protein-coupled estrogen receptor （GPR30） in ovarian cancer. [ Method] The expression of GPR30 was determinated by using immunohistochemistry in 110 epithelial ovarian cancers from our hospital. Thus, we correlated GPR30 expression with clinicopathological characteristics of ovarian cancer, especially in advanced and /or dedifferentiated ovarian cancer. Further, localization of GPR30 was described via immnnofluorescenee and FACS in ovarian cancer cell line SKOV-3. [Result] In brief, GPR30 expression was observed in 62.7% of ovarian cancer samples, containing 51 cases of serous adenocarcinoma and 4 cases of mucious adenocarcinoma （P = 0.102）. The expression of GPR30 was significantly elevated in R1 group （Residual tumor status positive） as compared to R0 group （Residual tumor status negative） patients （R1, 33/45; R0, 34/65; P = 0.030）. In addition, GPR30 was detected in 73.7% of recurrence-group, whereas 50.9% of non-recurrence patients had GPR30 expression. In spite of the GPR30 expression was observed more frequently in advanced ovarian cancer （FIGO III/IV） and dedifferentiated ovarian cancer （G3/4）, the difference didn＇t reach significant level. In 5-year survival we observed that 58.9% （33/56） of survival patient expressed GPR30 while expression of GPR30 was detected from 36 cases （66.7%） of dead. Furthermore, there was significant difference of GPR30 expression in intracellular of ovarian cancer cells. In addition, concentrated GPR30 was detected with great intensity around nucleus, rather than cytoplasm, of SKOV-3 cells. [Conclusion] GPR30 expression was observed more frequently in R1 group and recurrence-group of ovarian cancer. There was no significantly correlation between GPR30 expression and other characteristics of ovarian cancer, involving in FIGO stage, subtypes, grading level and response to chemotherapy. Moreover, intracellular GPR30 aggregating toward nucleus suggested a potential regulation for the progression of ovarian cancer.