Abstract
BackgroundThe aim of this study was to identify a biomarker useful in the diagnosis and therapy of ovarian malignant germ cell tumor (OMGCT).MethodsThe karyopherin 2 (KPNA2) expression in OMGCT and normal ovarian tissue was determined by standard gene microarray assays, and further validated by a quantitative RT-PCR and immunohistochemistry. The correlation between KPNA2 expression in OMGCT and certain clinicopathological features were analyzed. Expression of SALL4, a stem cell marker, was also examined in comparison with KPNA2.ResultsKPNA2 was found to be over-expressed by approximately eight-fold in yolk sac tumors and immature teratomas compared to normal ovarian tissue by microarray assays. Overexpression was detected in yolk sac tumors, immature teratomas, dysgerminomas, embryonal carcinomas, mature teratomas with malignant transformation and mixed ovarian germ cell tumors at both the transcription and translation levels. A positive correlation between KPNA2 and SALL4 expression at both the transcription level (R = 0.5120, P = 0.0125), and the translation level (R = 0.6636, P<0.0001), was presented. Extensive expression of KPNA2 was positively associated with pathologic type, recurrence and uncontrolled, ascitic fluid presence, suboptimal cytoreductive surgery necessity, resistance/refraction to initial chemotherapy, HCG level and SALL4 level in OMGCT patients. KPNA2 was found to be an independent factor for 5-year disease-free survival (DFS) of OMGCT (P = 0.02). The 5-year overall survival (OS) and DFS rate for KPNA2-low expression patients (88% and 79%, n = 48) were significantly higher than the OS and DFS rate for KPNA2-high expression patients (69% and 57.1%, n = 42)(P = 0.0151, P = 0.0109, respectively). The 5-year OS and DFS rate for SALL4-low expression patients (84% and 74%, n = 62) was marginally significantly higher than the high expression patients (78.6% and 71.4%, n = 28)(P = 0.0519, P = 0.0647, respectively).ConclusionsKPNA2 is a potential candidate molecular marker and important prognostic marker in OMGCT patients.
Highlights
The ovarian malignant germ cell tumor (OMGCT) is a rare, rapid-progressing, pathologically diverse, and highly malignant form of cancer frequent in younger women
KPNA2 was down-expressed in the normal ovarian specimens but extensively overexpressed in 2 yolk sac tumors and 2 immature teratomas (Figure 1A)
Two-sided Fisher’s exact test was applied to study the relationship between KPNA2 expression and the histological type, histological grade, clinical stage, recurrence, patient age, and optimal cytoreduction of OMGCT performed. Survival curves for both KPNA2- low expression and KPNA2- high expression patients were plotted using the Kaplan-Meier method and were analyzed for statistical differences using log-rank tests
Summary
The ovarian malignant germ cell tumor (OMGCT) is a rare, rapid-progressing, pathologically diverse, and highly malignant form of cancer frequent in younger women. Common histological types of OMGCT include yolk sac tumors, immature teratomas, dysgerminoma and mixed ovarian germ cell tumors. The etiology and development of OMGCT remain tumors, 38 immature teratomas, 11 dysgerminomas, 3 embryonal carcinomas, 10 mixed germ cell tumors, 8 mature teratomas with malignant transformation) hospitalized between 2000 and 2008 were included in this study for immunohistochemistry analysis. Patients diagnosed with OMGCT at the Sun Yat-Sen University. OMGCT tissues were dissected from the resected tumors, and normal ovarian specimens were obtained from apparently normal ovary tissue removed from other cervical carcinoma patients, after a pathological confirmation review. All samples were obtained from the Tissue Bank of Cancer Center, Sun Yat-Sen University. The aim of this study was to identify a biomarker useful in the diagnosis and therapy of ovarian malignant germ cell tumor (OMGCT)
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