Wang Shuai, Ma Xiao-Yan, Xia Yang, Zhang Li-Hong
Department of Obstetrics and Gynecology, Second Hospital of Jilin University, Changchun 130041, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2010 Jul;41(4):575-80.
To analyze the expressions of Ki67, PCNA and mitotic index in ovarian epithelial tumors and their relationship with clinical pathological features.
The expressions of Ki67, PCNA protein and mitotic index in ovarian tissues from 20 patients with normal ovarian tissues, 28 patients with ovarian benign tumors, 20 patients with borderline tumors and 109 (73 metastatic ovarian cancer) patients with malignant tumors were retrospectively tested using the American GBI immunohistochemistry two-step method. The expressions of Ki67 and PCNA mRNA were also detected by in situ hybridization (ISH) in ovarian tissues from 37 patients with primary ovarian cancer, 14 patients with borderline tumors, 11 patients with benign tumors and 12 patients with normal ovarian tissues. The relationship between clinical pathologic parameters and the expressions of Ki67 and, PCNA and mitotic index in human ovarian tumors was analyzed.
(1) The expressions of Ki67 mRNA and protein in ovarian epithelial tumors was higher than in the controls (P = 0.003; P = 0.009; P = 0.001; P = 0.001). But no significant differences appeared in the expression and overexpression of PCNA mRNA and pratein (P = 0.327; P = 0.718; P = 0.123; P = 0.125). Positive correlations between the expressions of mRNA and protein for Ki67 and PCNA were found (r = 0.449, P = 0.025; r = 0.484, P = 0. 014). (2) The expression of Ki67 in ovarian epithelial was higher in low differential carcinoma and at FIGO III-IV stage (P = 0.008; P = 0.007). The expression of Ki67 protein in serous tumor tissues was high, but low or missed in other types of tumor tissues such as malignant mixed mullerian tumor and transitional cell carcinoma (P = 0. 018). No significant differences in other clinicopathological features were found. The high expression of PCNA did not coincide with histological grading, clinical stage and histological types (P = 0.447; P = 0.763; P = 0.657). There were 72 patients with high mitotic index (66.1%). The high expression of mitotic index coincided with histological grading and clinical stage, but not with histological types (P = 0.002; P = 0.040). (3) The combined overexpression of Ki67 and high mitotic index occurred in 57 patients, which coincided with histological grading, clinical stage and histological types (P = 0.018; P = 0.001; P = 0.020). (4) In the 73 patients with metastatic ovarian cancers, the expressions of Ki67 (58.9%), PCNA protein (91.8%) and high MI (61.6%) in primary cancer tissues were greater than in the metastatic cancer tissues (peritoneum and epiploon, Ki67 41.4%, P = 0.031; PCNA 74%, P = 0.004; high MI 38.4%, P = 0.005). The positive intensity of Ki67 protein expression in primary ovarian cancers was significantly higher than in metastatic ovarian cancers (P = 0.040). There was no significant difference in positive intensity of PCNA between primary and metastatic ovarian cancers (P = 0.514).
Ki67 and mitotic index can serve as biomolecular markers for predicting the proliferation of malignant ovarian epithelial tumors. PCNA can not discriminate between benign and malinant ovarian tumors.
分析Ki67、增殖细胞核抗原（PCNA）及有丝分裂指数在卵巢上皮性肿瘤中的表达情况及其与临床病理特征的关系。
采用美国GBI免疫组织化学两步法，回顾性检测20例正常卵巢组织患者、28例卵巢良性肿瘤患者、20例交界性肿瘤患者及109例（其中73例为转移性卵巢癌）恶性肿瘤患者卵巢组织中Ki67、PCNA蛋白表达及有丝分裂指数。同时采用原位杂交（ISH）法检测37例原发性卵巢癌患者、14例交界性肿瘤患者、11例良性肿瘤患者及12例正常卵巢组织患者卵巢组织中Ki67和PCNA mRNA的表达。分析临床病理参数与人类卵巢肿瘤中Ki67、PCNA表达及有丝分裂指数的关系。
（1）卵巢上皮性肿瘤中Ki67 mRNA和蛋白表达高于对照组（P = 0.003；P = 0.009；P = 0.001；P = 0.001）。但PCNA mRNA和蛋白的表达及过表达无显著差异（P = 0.327；P = 0.718；P = 0.123；P = 0.125）。发现Ki67和PCNA的mRNA与蛋白表达呈正相关（r = 0.449，P = 0.025；r = 0.484，P = 0.014）。（2）低分化癌及国际妇产科联盟（FIGO）III-IV期卵巢上皮中Ki67表达较高（P = 0.008；P = 0.007）。浆液性肿瘤组织中Ki67蛋白表达高，而在其他类型肿瘤组织如恶性苗勒管混合瘤及移行细胞癌中表达低或缺失（P = 0.018）。其他临床病理特征未见显著差异。PCNA高表达与组织学分级、临床分期及组织学类型不一致（P = 0.447；P = 0.763；P = 0.657）。有72例患者有丝分裂指数高（66.1%）。有丝分裂指数高与组织学分级及临床分期一致，但与组织学类型不一致（P = 0.002；P = 0.040）。（3）Ki67与高有丝分裂指数联合过表达发生在57例患者中，与组织学分级、临床分期及组织学类型一致（P = 0.018；P = 0.001；P = 0.020）。（4）在73例转移性卵巢癌患者中，原发癌组织中Ki67（58.9%）、PCNA蛋白（91.8%）及高有丝分裂指数（61.6%）的表达高于转移癌组织（腹膜和网膜，Ki67 41.4%，P = 0.031；PCNA 74%，P = 0.004；高有丝分裂指数38.4%，P = 0.005）。原发性卵巢癌中Ki67蛋白表达的阳性强度显著高于转移性卵巢癌（P = 0.040）。原发性与转移性卵巢癌中PCNA的阳性强度无显著差异（P = 0.514）。
Ki67和有丝分裂指数可作为预测恶性卵巢上皮性肿瘤增殖的生物分子标志物。PCNA不能区分卵巢良性和恶性肿瘤。
