Abstract 334: Evaluation of ProEx C (MCM2 and TOP2A), p16 and Ki-67 as biomarkers for cervical carcinoma

Background: Cervical cancer is the second most common cancer among women worldwide. Many studies have confirmed a strong correlation between p16 overexpression and high-grade premalignant or malignant lesions of the cervix. A newer biomarker ProEx C has been implicated as a useful indicator for cervical cancer. However, data on comparison between these biomarkers in cervical cancer remain limited. In this study, we investigated the expression of ProExC, p16 and Ki-67 in cervical carcinoma and ovarian tumors as comparison. Objective: To determine the value of ProEx C combined with p16 and Ki-67 in detection of cervical carcinoma. Methods: Total of 28 cases of cervical carcinoma biopsies were included in this study, among these one was adenocarcinoma and 27 cases were squamous cell carcinoma type. Ovary tissue microarray (TMA) samples (BioGenex TS-4212) were used for comparison. ProEx C antibody cocktail was prepared from rabbit monoclonal antibodies against minichromosome maintenance protein 2 (MCM2, clone ID: EPR4120) and Topoisomerase II alpha (TOP2A, clone ID: EP1102Y). All tissue samples were examined for expression of p16 and Ki67. Co-localization of ProEx C/p16 and ProEx C/Ki-67 was determined by simultaneous double stain method. Fully automated Xmatrx® system was used for the IHC staining. Results: Overexpression of ProEx C was found in all 28 cases of cervical carcinoma tissues. All the cancer cells and some other proliferative cell types showed nucleus staining pattern. Upregulated expression of p16 was observed in all 28 cases, with both nucleus and cytoplasmic staining. The p16 staining was limited within those cancer cells. Simultaneous double stain for ProEx C/p16 demonstrated that over 90% of cancer cells co-expressing these two biomarkers. Although Ki-67 staining was also observed in all the cases, a variable portion (less than 50%) of cancer cells was Ki-67 positive. ProEx C/Ki-67 double positive cells were ranging from 20% to 40% of total ProEx C positive cells. Of the 41 ovary tissues from TMA, 35 were ovarian tumor samples and ProEx C positive, 17/35 was p16 positive (48.6%). Conclusions: 1) ProEx C is a sensitive proliferation biomarker for diagnosis of cancer, which is more sensitive in determining proliferation status than that of Ki-67. 2) p16 is a more specific biomarker for cervical carcinoma than that for ovarian cancer. 3) Combination of ProEx C and p16 may increase the sensitivity and specificity in cervical cancer detection. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 334. doi:10.1158/1538-7445.AM2011-334