PAX-8

This protein is a member of the paired box (PAX) family of transcription factors. Members of this gene family typically encode proteins which contain a paired box domain, an octapeptide, and a paired-type homeodomain. This nuclear protein is involved in thyroid follicular cell development and expression of thyroid-specific genes. Mutations in this gene have been associated with thyroid dysgenesis, thyroid follicular carcinomas, and atypical thyroid adenomas. PAX-8 is expressed in the thyroid (and associated carcinomas), non- ciliated mucosal cells of the fallopian tubes, and simple ovarian inclusion cysts, but not normal ovarian surface epithelial cells. PAX-8 is expressed in a high percentage of ovarian serous, endometrioid, and clear cell carcinomas, but only rarely in primary ovarian mucinous adenocarcinomas. Studies have also found PAX-8 expression in renal tubules as well as renal cell carcinoma, nephroblastoma, and seminoma. A study by Tong et al. showed that 98% of clear cell RCCs, 90% of papillary RCCs, and 95% of oncocytomas were positive for anti-PAX-8 with frequencies of positivity that are similar to anti-PAX-2. Therefore, anti-PAX-8 may be used as an additional immunohistochemical marker for renal epithelial tumors. Normal lung and lung carcinomas do not express PAX-8. Similarly, the absence of expression of PAX-8 in breast and other non-GYN carcinomas other than those primary to the thyroid indicates that anti-PAX-8 is an important new marker of ovarian cancer and a useful marker for the differential diagnoses in lung and neck tumors, or tumors at distant sites where primary lung carcinoma, breast carcinoma or thyroid carcinoma are possibilities. Anti-PAX-8, combined with organ system-specific markers such as anti-uroplakin III, anti- mammaglobin, and anti-TTF-1, can collectively serve as a very useful panel to determine the primary site of invasive micropapillary ovarian carcinomas from invasive carcinomas arising from bladder, lung, and breast.