Journal of American Science 2015;11(2) http://www.jofamericanscience.org 76 Immunoexpression of PAX-8 as a Useful Marker in Distinguishing Gynecological Malignancy from Colorectal Carcinomas: a Tissue Microarray-Based Approach Jaudah Al-Maghrabi 1,2,4 , Abdelbaset Buhmeida ,4 , Mohammad Al-Qahtani 4 and Mahmoud Al-Ahwal 1,3 1 Scientific Chair for Colorectal Cancer, King Abdulaziz University, Jeddah, Saudi Arabia 2 Departments of Pathology, 3 Medicine, King Abdulaziz University, Jeddah, Saudi Arabia 4 Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia jalmaghrabi@hotmail.com Abstract: Introduction: PAX 8 is a transcription factor that belongs to PAX gene family. The data on the diagnostic applications of PAX-8 is limited. In this study, the expression of PAX-8 in colorectal, endometrial and ovarian carcinomas is evaluated. Material and methods: Tissue microarrays were prepared from archival of colorectal carcinomas (n: 133), endometrial carcinomas (n: 79) and ovarian carcinomas (75) obtained from the Department of Pathology at King Abdulaziz University Jeddah, Saudi Arabia. Tissue sections were immunostained using monoclonal antibodies to PAX-8. The immunohistochemical stains were scored semiquantitatively from 0 to 4+. Results: PAX-8 immunoexpression was detected in 132/ 154 (83%) of the Mullerian carcinomas (93 and 43% for non-mucinous and mucinous carcinomas, respectively). PAX-8 expression was found in all serous carcinomas from ovarian and endometrial origin. PAX-8 was not detected in any of the colorectal carcinoma. Conclusion: PAX-8 is a sensitive marker for non-mucinous carcinomas of Mullerian origin and it is a useful marker in differentiating endometrial and ovarian carcinomas from colorectal carcinomas. [Jaudah Al-Maghrabi, Abdelbaset Buhmeida, Mohammad Al-Qahtani and Mahmou Al-Ahwal. Immunoexpression of PAX-8 as a Useful Marker in Distinguishing Gynecological Malignancy from Colorectal Carcinomas: a Tissue Microarray-Based Approach. J Am Sci 2015;11(2):76-81]. (ISSN: 1545-1003). http://www.jofamericanscience.org . 9 Key words: PAX-8, immunoexpression, colorectal, endometrial carcinoma, ovarian carcinoma, metastasis. 1. Introduction: PAX genes are a family of transcription factors that play critical roles during organogenesis. They are regulatory proteins expressed in embryonic or neoplastic cells of the same lineage. PAX-8 is crucial for organogenesis of the Müllerian system, kidney and thyroid gland. Few studies have demonstrated expression of PAX 8 in neoplasms including thyroid follicular neoplasm (1-4), renal cell carcinoma (5), nephrogenic adenoma (6-12), Wilms’ tumors (13), and ovarian carcinoma (14-17). Gynecological malignancies (endometrial and ovarian) and colorectal carcinomas are among the common malignancies in women. Distinction between metastasis from gynecological malignancies and colorectal carcinomas is important as their prognoses differ significantly. It is important to differentiate metastatic Mullerian tumors from metastatic colorectal carcinoma in liver, lung or peritoneum. It is also important to differentiate primary Mullerian tumors from metastatic colorectal cancer to the ovaries. The data on the expression of PAX-8 in colorectal and gynecological malignancies is limited. We applied PAX-8 immunostain on a large number of ovarian, endometrial and colorectal carcinomas to evaluate the diagnostic significance. 2. Patients and Methods The study included paraffin wax blocks of colorectal carcinomas (n: 133), endometrial (n: 79) and ovarian (75). Tumor specimens represent the surgical treatment of patients with no prior chemotherapy or radiotherapy given. Blocks were retrieved from the archives of the Department of Pathology at King Abdulaziz University, Jeddah, Saudi Arabia. The study was approved by the Research Committee of the Biomedical Ethics Unit, Faculty of Medicine, King Abdulaziz University. Tissue Microarray: Tissue microarrays (TMA) were designed and constructed as previously described (18). Briefly, hematoxylin and eosin-stained sections of endometrial carcinomas, ovarian carcinomas, normal colorectal mucosae, colorectal adenomas, and primary tumors and nodal metastasis were reviewed by an experienced pathologist. Areas of interest were chosen from the original blocks and were marked on the slides. Necrotic, autolytic areas and areas containing predominantly the stromal tissue were avoided. Tissue cores each 1.5 mm in diameter were punched from donor block (s) in an automated TMA instrument (TMA Master 1.14 SP3 from 3D Histech Ltd. Budapest, Hungary) and inserted into a recipient paraffin block. Placenta was used for orientation. Slides were cut from TMA block and stained with