PAX8 Is Highly Sensitive and Specific for Mullerian, Renal and Thyroid Neoplasms: A Study of 1500 Epithelial Tumors
AR Laury, JL Hornick, H Piao, R Perets, J Barletta, LR Chirieac, JF Krane, R Lis, M Loda, R Drapkin, MS Hirsch. Brigham and Womens Hospital, Boston, MA; Dana Farber Cancer Institute, Boston, MA
Background: PAX8 is a paired homeobox gene critical for development of the thyroid and urogenital tract. Expression has been described in tumors of the kidney, thyroid and Mullerian tract, but a large study, including a wide variety of epithelial neoplasms from multiple organs, to address specificity has not been performed.
Design: PAX8 immunohistochemistry was performed, after pressure cooker antigen retrieval using a rabbit anti-PAX8 polyclonal antibody (Proteintech; 1:800) on formalin-fixed, paraffin embedded tissue from 1500 tumors retrieved from department files. These 1500 cases included 701 whole tissue sections and 799 tumors in tissue microarrays from multiple organs. Only nuclear staining was scored as positive. Western blot analysis with PAX8 was also performed on renal, ovarian, prostatic, breast, colonic, cervical, and brain tumor cell lines.
Results: Nuclear PAX8 staining was present in 94% (58/62) of thyroid tumors, 61% (95/155) of renal cell carcinomas, 80% (12/18) of oncocytomas, 99% (151/152) of high grade ovarian serous carcinomas, and 38% (58/152) of endometrial adenocarcinomas. Of the remaining 961 evaluated tumors, only 15 cases (1.6%) demonstrated weak or focal PAX8 positivity. These 15 cases included 3 bladder urothelial carcinomas, 4 lung squamous cell carcinomas, 2 esophageal adenocarcinomas, 1 pancreatic adenocarcinoma, 1 ovarian Sertoli-Leydig cell tumor, 3 testicular mixed germ cell tumors, and 1 acinic cell carcinoma. All 946 remaining tumors, including, but not limited to those from the prostate, colon, stomach, liver, adrenal gland, and head and neck, as well as small cell carcinomas from the lung, cervix, and ovary, were PAX8 negative. PAX8 specificity was confirmed by Western blot analysis, as expression was only detected in ovarian and renal cell carcinoma lines.
Conclusions: PAX8 is a highly sensitive marker for ovarian serous and thyroid carcinomas, but is also expressed in a significant proportion of renal and other Mullerian tumors. Importantly, all lung adenocarcinomas, breast and adrenal neoplasms, as well as the majority (148/151) of GI tumors were negative for PAX8. Therefore, strong PAX8 expression is excellent for confirming site of tumor origin. In a subset of cases, additional markers such as TTF-1, RCC, and WT-1 may be needed to distinguish among the 3 most common PAX8-positive tumors.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 227, Wednesday Morning