[Expressions of Ki67, PCNA and mitotic index in ovarian epithelial tumors].
OBJECTIVE
To analyze the expressions of Ki67, PCNA and mitotic index in ovarian epithelial tumors and their relationship with clinical pathological features.


METHODS
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.


RESULTS
(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).


CONCLUSIONS
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.
Wang
Shuai
S
Department of Obstetrics and Gynecology, Second Hospital of Jilin University, Changchun 130041, China.
Ma
Xiao-Yan
XY
Xia
Yang
Y
Zhang
Li-Hong
LH
D014408:Biomarkers, Tumor / Q000096:biosynthesis; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism*; D008940:Mitotic Index; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen