蛋白酪氨酸激酶PTK7在卵巢浆液性肿瘤中的表达及意义

背景与目的：新近发现的蛋白酪氨酸激酶-7(protein tyrosine kinase-7，PTK7)基因与多种肿瘤的发生、发展和浸润有关。本研究旨在探讨PTK7在卵巢浆液性肿瘤中的表达及其与临床分期、组织学分级、转移和预后等指标的关系，分析PTK7表达在卵巢浆液性肿瘤中的诊断及预后价值。方法：制备3株卵巢癌细胞系(HO8910、SKOV3、A2780)爬片，并收集14例正常输卵管上皮组织，6例良性浆液性卵巢肿瘤，51例交界性浆液性卵巢肿瘤和97例卵巢浆液性癌组织蜡块，采用免疫组化EliVision两步法检测PTK7蛋白的表达，结合相关病理指标，采用χ²检验、Fisher确切概率法、Kaplan-Meier法进行统计分析。结果：PTK7在卵巢癌细胞株HO8910及A2780中呈阴性表达，在SKOV3中成弱阳性表达。PTK7在92.86%(13/14)的正常输卵管上皮、83.33%(5/6)的良性浆液性卵巢肿瘤、45.10%(23/51)的交界性浆液性卵巢肿瘤和28.87%(28/97)的浆液性卵巢癌中阳性表达。正常输卵管上皮与良性浆液性肿瘤、良性浆液性肿瘤与交界性浆液性肿瘤之间PTK7表达差异无统计学意义(P=0.521，P=0.102)。浆液性卵巢癌与正常输卵管上皮、良性浆液性肿瘤以及交界性浆液性肿瘤之间PTK7表达差异有统计学意义(P=0.000，P=0.012，P=0.048)。PTK7在交界性浆液性卵巢肿瘤中的表达与其临床分期、淋巴结和(或)腹膜转移情况有关(P=0.038，P=0.038)，与其发生部位、年龄无关(P=0.088，P=0.896)。PTK7在卵巢浆液癌中的表达与其临床分期、WHO分级、MDACC病理分级有关(P=0.011，P=0.004，P=0.000)，与其发生部位、转移情况、肿瘤直径、年龄无关(P=0.326，P=0.524，P=0.588，P=0.584)。卵巢浆液癌中PTK7阳性组的生存率显著高于阴性组(P=0.017)。结论：PTK7在输卵管正常上皮、良性浆液性卵巢肿瘤、交界性浆液性卵巢肿瘤和浆液性癌中表达呈逐步下调趋势。PTK7表达与卵巢上皮性浆液性肿瘤的较晚临床分期、高组织分级、预后差呈正相关，可能成为卵巢浆液性肿瘤辅助诊断及临床预后的新指标。

Expression and clinical significance of PTK7 in ovarian serous tumors

Background and purpose: The protein tyrosine kinase-7 (PTK7) gene may be related to the occurrence and progression of many tumors. This study was aimed to explore the expression of PTK7 in ovarian serous tumors and its relationship with clinical stage, histological grade, metastasis and prognosis indicators linkages, and analyze the diagnostic and prognostic value of PTK7 in ovarian serous tumors. Methods: Expressions of PTK7 in 3 ovarian cell lines (HO8910, SKOV3, A2780), 14 cases of normal fallopian tube epithelium, 6 cases of benign serous ovarian tumors, 51 cases of borderline serous ovarian tumors and in 97 cases of ovarian serous carcinoma were detected by immunohistochemical EliVision two-step method. Statistical analysis of the relationship between the expression of PTK7 and the pathological indicators was performed by χ² test, Fisher exact test and Kaplan-Meier method. Results: PTK7 was negatively expressed in HO8910 and A2780, but weakly positively expressed in SKOV3. The positive rates of PTK7 in normal fallopian tube epithelium, benign serous ovarian tumors, borderline serous ovarian tumors and serous ovarian cancer were 92.86% (13/14), 83.33% (5/6), 45.10% (23/51), and 28.87% (28/97), respectively. The expression of PTK7 had no difference between normal fallopian tube epithelium and benign serous tumors, benign serous tumors and serous borderline tumors (P=0.521, P=0.102). The PTK7 expression showed significant differences in serous ovarian carcinoma compared with those in normal epithelium, benign serous tumors and borderline serous tumors (P=0.000, P=0.012, P=0.048). Expression of PTK7 in borderline serous ovarian tumors was significantly with clinical stage, metastasis (lymph node and/or peritoneum metastasis) (P=0.038, P=0.038), rather than its location, age (P=0.088, P=0.896). Expression of PTK7 in ovarian serous carcinoma had a significant relation with its clinical stage, WHO grade, MDACC grade (P=0.011, P=0.004, P=0.000), rather than its location, metastasis, tumor diameter and age (P=0.326, P=0.524, P=0.588, P=0.584). The survival rate of PTK7 positive group in ovarian serous carcinoma was significantly higher than that in the negative control group (P=0.017). Conclusion: The expressions of PTK7 in normal ovarian epithelium, benign serous ovarian tumors, borderline serous ovarian tumors and epithelial serous carcinoma show a gradual downward trend. The expression of PTK7 in ovarian serous tumors has a positive correlation with late clinical stage, high histological grade and poor prognosis. PTK7 can be a new indicator of clinical diagnosis and prognosis in ovarian serous tumors.