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ObjectiveTo investigate the changes of incidence and prognosis of epithelial ovarian cancer in thirty years in Taiwan.MethodsThe databases of women with epithelial ovarian cancer during the period from 1979 to 2008 were retrieved from the National Cancer Registration System of Taiwan. The incidence and prognosis of these patients were analyzed.ResultsTotally 9,491 patients were included in the study. The age-adjusted incidences of epithelial ovarian cancer were 1.01, 1.37, 2.37, 3.24, 4.18, and 6.33 per 100,000 person-years, respectively, in every 5-year period from 1979 to 2008. The age-specific incidence rates increased especially in serous, endometrioid and clear cell carcinoma, and the age of diagnosis decreased from sixty to fifty years old in the three decades. Patients with mucinous, endometrioid, or clear cell carcinoma had better long-term survival than patients with serous carcinoma (log rank test, p<0.001). Patients with undifferentiated carcinoma or carcinosarcoma had poorer survival than those with serous carcinoma (log rank test, p<0.001). The mortality risk of age at diagnosis of 30-39 was significantly higher than that of age of 70 years or more (test for trend, p<0.001). The mortality risk decreased from the period of 1996-1999 (hazard ratio [HR], 0.90; p=0.054) to the period after 2000 (HR, 0.74; p<0.001) as compared with that from the period of 1991-1995.ConclusionAn increasing incidence and decreasing age of diagnosis in epithelial ovarian cancer patients were noted. Histological type, age of diagnosis, and treatment period were important prognostic factors for epithelial ovarian carcinoma.

The objective of this paper is to investigate the mesothelin expression level to the clinicopathological features, chemoresponse, and to the outcome of patients with epithelial ovarian carcinoma (EOC). Mesothelin mRNA was detected by real-time quantitative reverse-transcription PCR in 139 EOC patients. Clinical characteristics, histopathological items, responses to chemotherapy, progression-free survival (PFS), and overall survival (OS) were recorded. Tumours with advanced stages had higher mesothelin than those with early stages. The chemoresistant patients showed significantly higher mesothelin than did chemosensitive patients (2.81 vs 0.43, Po0.001), irrespective of optimal or suboptimal surgery in those with advanced stages. Highly expressed levels of mesothelin were an independent but poor prognostic factor in the PFS (2.03 (1.23 -3.37) P ¼ 0.006) and ), P ¼ 0.002) of the 139 EOC patients in multivariate analysis. In addition, patients in advanced stages with highly expressed mesothelin also had significantly worse OS, regardless of whether they had undergone optimal (13.85 (1.76 -125.60), P ¼ 0.013) or suboptimal (4.47 (1.83 -10.88), P ¼ 0.001) debulking surgery in multivariate analysis. Out results provide new evidence that mesothelin expression is associated with chemoresistance and with shorter disease-free survival and worse OS of patients with EOC.

Ovarian cancer has one of the highest mortalities in malignancies in women, but little is known of its tumour progression properties and there is still no effective molecule that can monitor its growth or therapeutic responses. MSLN (mesothelin), a secreted protein that is overexpressed in ovarian cancer tissues with a poor clinical outcome, has been previously identified to activate PI3K (phosphoinositide 3-kinase)/Akt signalling and inhibit paclitaxel-induced apoptosis. The present study investigates the correlation between MSLN and MMP (matrix metalloproteinase)-7 in the progression of ovarian cancer, and the mechanism of MSLN in enhancing ovarian cancer invasion. The expression of MSLN correlated well with MMP-7 expression in human ovarian cancer tissues. Overexpressing MSLN or ovarian cancer cells treated with MSLN showed enhanced migration and invasion of cancer cells through the induction of MMP-7. MSLN regulated the expression of MMP-7 through the ERK (extracellular-signal-regulated kinase) 1/2, Akt and JNK (c-Jun N-terminal kinase) pathways. The expression of MMP-7 and the migrating ability of MSLN-treated ovarian cancer cells were suppressed by ERK1/2- or JNK-specific inhibitors, or a decoy AP-1 (activator protein 1) oligonucleotide in in vitro experiments, whereas in vivo animal experiments also demonstrated that mice treated with MAPK (mitogen-activated protein kinase)/ERK- or JNK-specific inhibitors could decrease intratumour MMP-7 expression, delay tumour growth and extend the survival of the mice. In conclusion, MSLN enhances ovarian cancer invasion by MMP-7 expression through the MAPK/ERK and JNK signal transduction pathways. Blocking the MSLN-related pathway could be a potential strategy for inhibiting the growth of ovarian cancer.