Different clinical roles for p21-activated kinase-1 in primary and recurrent ovarian carcinoma

We recently found amplification of chromosome 11q13.5 in high-grade ovarian serous carcinoma. In the present study, we analyzed the protein expression and clinical significance of p21-activated kinase-1, one of the genes amplified at this site. Formalin-fixed paraffin-embedded sections from 186 effusions (152 peritoneal, 34 pleural) were immunostained. p21-Activated kinase-1 expression in tumor cells was analyzed for possible association with clinicopathologic parameters and survival. The association between protein expression of p21-activated kinase-1 and Rsf-1, a chromatin remodeling protein whose gene colocalizes with p21-activated kinase-1, was additionally studied. p21-Activated kinase-1 protein expression was found in carcinoma cells in 158 (85%) of 186 effusions. Of these, 62 (39%) stained weakly and 96 (61%) strongly. p21-Activated kinase-1 was coexpressed with Rsf-1 (P = .006). Specimens from patients diagnosed with International Federation of Gynecology and Obstetrics stage IV disease had higher staining intensity compared with stage III tumors (P = .014). Univariate survival analysis for patients with primary diagnosis prechemotherapy effusions demonstrated a significant association between higher p21-activated kinase-1 staining extent and longer overall survival (P = .024). In addition, higher staining extent (P = .015) and intensity (P = .013) correlated with better progression-free survival. In contrast, higher p21-activated kinase-1 staining extent correlated with poor overall survival in disease recurrence postchemotherapy effusions (P = .044). In Cox analysis, higher p21-activated kinase-1 staining extent independently correlated with longer progression-free survival (P = .016) and shorter overall survival (.049) in primary diagnosis and disease recurrence effusions, respectively. p21-Activated kinase-1 is frequently expressed in ovarian carcinoma cells in effusions and is associated with opposite prognostic role in primary and recurrent disease. This suggests altered cellular function for this kinase along disease progression, possibly chemotherapy mediated.