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Tissue microarray (TMA) is a promising technique in the evaluation of immunohistochemical markers in tumors and may be used as an alternative for whole sections. However, only a few studies have correlated a clinical outcome with both TMA and results obtained from whole sections. This study compared immunostaining for Ki-67 and p16 in TMA (3 cores from each specimen) and whole sections of 171 cases of stage III epithelial ovarian cancer with clinical data. A high expression of Ki-67 was identified in 85.0, 85.5, 85.8, 90.5 and 84% of cores 1, 2 and 3, TMAs and whole tissue sections, respectively. A high p16 expression was found in 36.5, 31.4, 30.3, 46.3 and 31.0% of cores 1, 2 and 3, TMAs and whole tissue sections, respectively. The high expression of Ki-67 and p16 in whole tissue sections significantly correlated with that of Ki-67 and p16 in core 1 (P<0.0001 and P<0.0001, respectively), core 2 (P<0.0001 and P<0.0001, respectively), core 3 (P<0.0001 and P<0.0001, respectively), and TMAs (P<0.0001 and P<0.0001, respectively). In univariate analysis, a high expression of Ki-67 and p16 in two of the cores; TMA and the whole tissue sections were significantly correlated to disease-related survival (Ki-67: P=0.008, 0.012, 0.012 and 0.0001, respectively, and p16: P=0.0007, 0.0005, 0.0008 and 0.005, respectively). However, in the multivariate analysis only Ki-67 on whole tissue sections retained an independent prognostic significance (P=0.025). We concluded that more studies, with a higher number of cores, are necessary to determine the efficacy of TMA in reflecting the prognostic value of different antibodies. Morever, evaluation of this method is crucial for each type of tumor and each separate antigen. It is also essential to confirm the clinical correlations on the whole sections before investigating the same parameters on TMA.

Using gene expression arrays, we recently showed that MUC4 expression is significantly higher in ovarian/primary peritoneal serous carcinoma (OC/PPC) compared to diffuse peritoneal malignant mesothelioma (DMPM). In the present study, we analyzed the anatomic site-related expression of MUC4 in OC/PPC and studied its prognostic role. We additionally studied the ability of MUC4 to differentiate between OC/PPC and reactive mesothelial cells (RMC). OC/PPC effusions (n = 142) and benign reactive effusions (n = 10) were immunostained for MUC4 expression. Immunoreactivity was scored in carcinoma cells and RMC and was compared with tumor cell expression in 60 previously studied primary carcinomas and solid metastases and analyzed for association with clinicopathologic parameters, including survival. MUC4 was detected in carcinoma cells in 141/142 (99%) effusions, with comparable expression in peritoneal and pleural effusions. RMC were present in 72 malignant effusions and were MUC4-negative in all specimens, as well as in the 10 reactive effusions. MUC4 expression in carcinoma cells in effusions was significantly higher than in primary carcinomas and solid metastases (P < 0.001). Higher MUC4 expression was seen in tumors from older (>60 year) patients (P = 0.049). No association was found between MUC4 expression and other clinicopathologic parameters, including survival. MUC4 is universally expressed in OC/PPC effusions and is upregulated at this anatomic site compared to primary carcinomas and solid metastases. The data in the present study, together with our earlier report, show that MUC4 is an excellent marker for differentiating OC/PPC from both benign and malignant mesothelial cells., (Copyright 2007 Wiley-Liss, Inc.)

The present study addressed the impact of p14, p16, p57, and Ki-67 in a large cohort of uniformly treated patients with stage III ovarian cancer in relation to other clinicopathologic variables and prognosis. We immunohistochemically studied 171 primary tumors from previously untreated patients with advanced ovarian carcinomas for expression of Ki-67, p16, p14, and p57. High protein levels of Ki-67 (>10% positive nuclei) were found in 144 cases (84%), p16 (>50% positive nuclei) in 53 cases (31%), p57 (>10% positive nuclei) in 41 cases (24%), and p14 (any positive nuclei) in 19 cases (11%). A correlation between high Ki-67 expression and presence of residual disease after primary surgery (P = 0.019), ascites (P = 0.006), higher International Federation of Gynecology and Obstetrics substage (P < 0.001), poor differentiation (P < 0.001), and higher Silverberg histopathologic grade (P < 0.0001) was seen. High expression of p16 correlated to poor differentiation (P = 0.033) and higher Silverberg histopathologic grade (P = 0.018). In univariate analysis, high expression of Ki-67 (P = 0.0001) and p16 (P = 0.005) was associated with poor survival. However, in multivariate analysis, only high expression of Ki-67 was significantly associated with shorter survival (P = 0.025). No correlations were seen between expression of p14 and p57 and clinicopathologic parameters. None of the factors studied was able to predict response to chemotherapy. Our results showed that Ki-67 represents an independent prognostic predictor in stage III ovarian cancer. We did not find p16, p14, and p57 to be useful as prognostic markers.