Prostaglandin D2 expression is prognostic in high­grade serous ovarian cancer.

To identify biomarkers that could predict response or lack of response to conventional chemotherapy at the time of diagnosis of high­grade serous ovarian carcinoma (HGSOC), the present study compared large­scale gene expression from patients with short or long disease­free survival times, according to the last cycle of chemotherapy, and validated these findings using reverse transcription­quantitative polymerase chain reaction (RT­qPCR) and conventional immunohistochemical (IHC) analysis. Samples were selected for microarray evaluation, at the time of diagnosis, using the following criteria: Identical debulking primary surgery, International Federation of Gynaecology and Obstetrics staging, histological subtype and grade. These were divided into 2 groups, regarding the outcome after 2 years of follow-up. Prostaglandin D2 synthase 21 kDa (brain) (PTGDS) was found to be expressed at a significantly higher level in the tumours of patients with a short disease­free survival time, and this was validated by RT­qPCR in all samples. Furthermore, the study evaluated PGD2, the protein product of the PTGDS gene, in a large cohort of 114 HGSOC patients using the Ventana Benchmark automated platform, and IHC positivity was correlated with clinicopathological data and outcome. The global gene expression analysis identified 1,149 genes that were differentially expressed in microarray data, according to the patient outcome. Further analysis RT­qPCR validated PTGDS gene expression in the same samples (r=0.945; P<0.001). IHC analysis showed an inverse profile, with positivity for PGD2 strongly associated with an increase in disease­free survival (P=0.009), the absence of relapse (P=0.039) and sensitivity to platinum­based therapy (P=0.016). Multiple Cox regression showed that IHC evaluation of PGD2 was also a prognostic marker associated with relapse (hazard ratio, 0.37; P=0.002). Overall, the results showed that IHC evaluation of PGD2 is an independent marker of good prognosis in HGSOC. This finding contributes to our understanding of the mechanism of tumour regulation and to investigations into biomarkers that predict response to chemotherapy.

Downregulation of AGR2, p21, and cyclin D and alterations in p53 function were associated with tumor progression and chemotherapy resistance in epithelial ovarian carcinoma.

Anterior gradient 2 protein belongs to a family of chaperone-like proteins, namely protein disulfide isomerase. Generally, AGR2 is highly expressed in mucus-secreting cells and endocrine organs, and in this study, we aimed to evaluate AGR2 and cell cycle molecules in epithelial ovarian cancer and its implications on prognosis. One hundred seventy-five patient's samples that were diagnosed with primary epithelial ovarian carcinoma were selected. All the patients were treated with platinum-taxane standard chemotherapy after surgery and CA125 serum levels were routinely determined. Four-micrometer-thick sections were processed by immunohistochemistry using an automated immunostainer, Ventana BenchMark AutoStainer with AGR2, cyclin D1, p21WAF1, and p53. Forty-nine of 167 cases (29.3%) showed strong to moderate cytoplasmic marking of AGR2, and 118 (70.7%) had weak to negative expression. The absence of the AGR2 protein was observed in high-grade serous carcinoma (P < .001) and significantly associated with disease-free survival (DFS; P = .034). The expression of G1-S phase-regulatory proteins showed loss of p21 in high-grade serous carcinoma (P < .001) and was related with poor DFS (P = .003). Strong and diffuse immunoexpression of p53 plus complete absence of p53 staining was interpreted as likely indicating a TP53 gene mutation. This result showed worse DFS alone (P = .012) and combined with low levels of AGR2 (P = .005). The expression profile of AGR2 and cell cycle proteins here presented was showed as good prognosis marker in epithelial ovarian cancer. This finding suggests AGR2 and as putative biomarker of disease progression in chemotherapy-treated high-grade serous carcinoma patients.