摘要
背景与目的:失巢凋亡抑制因子酪氨酸激酶受体B(tyrosine kinase receptor, TrkB)能诱导正常上皮细胞的恶性转化并且使该细胞具有高转移能力。TrkB在良性肿瘤中及正常卵巢上皮中不表达,在癌组织中不但表达,并且与交界性肿瘤比较表达明显增高;转移灶和低分化癌组织中明显增高,如在神经母细胞瘤和其它多种人类高侵袭性恶性肿瘤组织中过度表达,本研究旨在探讨其过度表达与肿瘤组织分化及病人预后的关系。方法:选取卵巢癌石蜡标本73例(包括与原发灶相对应的8例腹水中的癌细胞团簇),其中低分化腺癌34例,28例卵巢交界性上皮性肿瘤;16例卵巢良性上皮性肿瘤及13例正常卵巢组织作为对照,行免疫组化ABC法检测TrkB的表达;随机选取上述病例中30例(包括4例与原发灶相对应的大网膜转移灶和腹水中的癌细胞团簇)、交界性上皮性肿瘤7例;卵巢良性上皮性肿瘤4例及正常卵巢组织(包括卵巢皮质和髓质)2例作为对照,行RT-PCR检测TrkB的表达。结果:RT-PCR结果表明,TrkB mRNA在卵巢癌与卵巢交界性肿瘤中的相对转录水平分别为(16.7±3.1)%和(4.6±0.4)%,在卵巢癌组织中表达明显增加(P<0.001);TrkB mRNA在大网膜转移灶和腹水中的癌细胞团簇中的TrkB mRNA相对表达量分别为(31.4±1.4)%和(28.2±0.7)%,与相应的原发灶(18.1±1.1)%比较,差异有显著性(P<0.001)。免疫组化结果表明,卵巢良性上皮性肿瘤及正常卵巢上皮不表达TrkB;TrkB在卵巢上皮性癌及卵巢交界性上皮性肿瘤组织中的阳性表达率分别为67.12%(49/73)和14.29%(4/28),两者比较差异有显著性(P<0.001),TrkB前体蛋白(表达于胞质)广泛地高表达于卵巢上皮性癌组织中67.12%(49/73),全长TrkB蛋白(表达于胞膜)在腹水中的癌细胞团簇100%(8/8)和低分化卵巢癌组织中100%(34/34)表达增强,与原发灶49.32%(36/73)和高分化癌7.69%(3/39)比较,差异有显著性(P<0.01)。TrkB阳性表达与卵巢�
Background and purpose.. TrkB, a neurotrophic tyrosine kinase receptor, serves as a potent and specific suppressor of anoikis of non-malignant epithelial cells, and confers high metastatic capacity to these cells. TrkB over-expression has been found in neuroblastoma and some other high aggressive cancers. This study was to investigate the expression and significance of anoikis-suppressor TrkB in human epithelial ovarian cancer, as well as to evaluate its association with differentiation of ovarian cancer and disease outcome. Methods: The expression of TrkB protein was examined in epithelial ovarian cancer specimens by immunohistochemical staining (ABC method), and confirmed by RT-PCR at mRNA level. Results: TrkB mRNA was overexpressed in epithelial ovarian cancer specimens, especially in greater omentum metastatic lesions and multicellular spheroids in ascites, and the ratios of TrkB to 13-actin were (31.4±1.4)% and (28.2±0.7)% respectively, compared with corresponding lesions that was (18.1±1.1)% (P〈0.001). In addition, there was a significant difference of TrkB mRNA between epithelial ovarian cancer specimens and borderline epithelial ovarian tumors, (16.7±3.1)% versus (4.6±0.4)% (P〈0.001) by RT- PCR. The positive rate of TrkB in patients with epithelial ovarian cancer and borderline epithelial ovarian tumors were 67.12%(49/73) and 14.29%(4/28) respectively, had a significant difference between them (P〈0.001). Full-length TrkB protein (glycosylated receptor expressed on membrane) was more often overexpressed in multicellular spheroids in ascites(8/8) and high grade carcinomas(34/34) than that in corresponding primary carcinoma(36/73) and low grade carcinomas (3/39,P〈0.01), but TrkB protein precursor (non-glycosylated receptor expressed in cytoplasm) was overexpressed extensively in epithelial ovarian cancer specimens(49/73) by IHC.The overexpression of TrkB in patients with epithelial ovarian cancer correlated with their ba
出处
《中国癌症杂志》
CAS
CSCD
2008年第7期501-506,共6页
China Oncology
基金
上海市卫生局重点研究项目(2005ZD002)
国家自然科学基金资助项目(30371482)