Dipeptidyl peptidase IV (DPPIV; also known as cluster of differentiation 26) and the surface-expressed protease, seprase [also known as fibroblast activation protein alpha (FAPα)], are able to degrade the extracellular matrix; therefore, they are involved in malignant cell invasion and metastasis. However, the prognostic implications of their overexpression in carcinomas remain controversial. The aim of the present study was to investigate the expression and potential prognostic effects of DPPIV and seprase in cases of ovarian carcinoma. Immunohistochemical analysis (IHC) was performed to assess the protein expression of DPPIV and seprase/FAPα in 199 patients (malignant epithelial ovarian cancer, 128; borderline ovarian tumors, 41; and benign ovarian tumors, 30). In addition, in situ hybridization was used to detect the mRNA expression levels of DPPIV and seprase in 86 malignant epithelial ovarian cancer samples. IHC revealed positive staining for seprase and DPPIV proteins in 110/128 (85.94%) and 106/128 (82.81%) patients with ovarian cancer, respectively. Seprase and DPPIV protein expression was associated with lymph node metastasis and the International Federation of Gynecology and Obstetrics stage. By contrast, no significant correlation was detected between the proteins and the patient age or histological grade and type of tumor. Immunostaining was stronger in the cancerous tissues compared with the borderline and benign tissues. Increased levels of seprase, but not DPPIV, were significantly associated with a shorter disease-free survival (P=0.033). Further analysis revealed that 96.5 (83/86) and 97.67% (84/86) of the malignant epithelial ovarian cancer samples stained positively for seprase and DPPIV mRNA, respectively. Therefore, DPPIV and seprase may be involved in the development of ovarian cancer, and that they are potential predictive markers of epithelial ovarian carcinoma.
Keywords: dipeptidyl peptidase IV; ovarian carcinoma; seprase.