A Comprehensive Analysis of PAX8 Expression in Human Epithelial Tumors

Abstract

PAX8 is a paired-box gene important in embryogenesis of the thyroid, Müllerian, and renal/upper urinary tracts, and expression of PAX8 has been previously described in carcinomas from each of these sites. However, a large study including a wide variety of epithelial neoplasms from multiple organ sites other than the thyroid, kidney, or Müllerian system has not been performed. The goal of this study was to evaluate the utility of PAX8 immunostaining based on the evaluation of a wide range of epithelial tumors. PAX8 immunohistochemistry was performed on 1357 tumors (486 tumors in whole-tissue sections and 871 tumors in tissue microarrays, predominantly epithelial) from multiple organs. Only nuclear staining was scored as positive, and tumors were evaluated for the extent and intensity of staining. Western blot analysis with PAX8 was also performed on multiple tumor cell lines. Nuclear PAX8 staining was present in 91% (60 of 66) of thyroid tumors, 90% (158 of 176) of renal cell carcinomas (RCCs), 81% (13 of 16) of renal oncocytomas, 99% (164 of 165) of high-grade ovarian serous carcinomas, 71% (32 of 49) of nonserous ovarian epithelial neoplasms, 91% (10 of 11) of cervical epithelial lesions, and 98% (152 of 155) of endometrial adenocarcinomas. Of the remaining 719 evaluated tumors, only 30 cases (4%), including 12 thymic neoplasms, 3 bladder urothelial carcinomas, 4 lung squamous cell carcinomas, 2 esophageal adenocarcinomas, 1 pancreatic adenocarcinoma, 2 cholangiocarcinomas, 1 ovarian Sertoli-Leydig cell tumor, 1 ovarian sex cord stromal tumor, 3 testicular mixed germ cell tumors, and 1 acinic cell carcinoma, showed at least weak or focal PAX8 positivity. The unexpected finding was diffuse, moderate staining of PAX8 in a subset of thymomas and thymic carcinomas. The 689 remaining tumors, including but not limited to those from the prostate, colon, stomach, liver, adrenal gland, and head and neck, and small cell carcinomas from the lung, cervix, and ovary, were PAX8 negative. PAX8 specificity was confirmed by Western blot analysis, as expression was detected only in ovarian and RCC cell lines. These results show that PAX8 is a highly sensitive marker for thyroid, renal, Müllerian, and thymic tumors. Importantly, all lung adenocarcinomas, breast and adrenal neoplasms, and the majority of gastrointestinal tumors were negative for PAX8. Therefore, PAX8 is an excellent marker for confirming primary tumor site. In a subset of cases, additional markers, including but not limited to thyroid transcription factor-1, RCC, and Wilms tumor-1, may be needed to distinguish between the 3 most common PAX8-positive tumors.

Comparative immunohistochemical analysis of pulmonary and thymic neuroendocrine carcinomas using PAX8 and TTF-1

“…PAX8 is a transcription factor that is commonly expressed in epithelial tumors of the thyroid gland, parathyroid gland, kidneys and Mü llerian tract. 24,[32][33][34] In addition, PAX8 has recently also been described to label neoplastic epithelial cells of thymic epithelial neoplasms. 35 Interestingly, PAX8 expression has also been described in a subset of neuroendocrine neoplasms, such as pancreatic neuroendocrine tumors as well as duodenal and rectal carcinoid tumors.…”

Assessment of the Utility of PAX8 Immunohistochemical Stain in Diagnosing Endocervical Glandular Lesions

“…Earlier studies showed that PAX8 positivity ranges from 97% to 100% in AIS and 0% to 87% in ECA. [1][2][3][4][5][6][7][8][9] The discrepancies among various studies may be attributable to several factors; the first is small sample size. Our study included 43 ECA (combined 2 cohorts) and 16 AIS, and is one of the largest studies.…”

“…2 Furthermore, PAX8 was expressed in 97% to 100% of adenocarcinoma in situ (AIS) and in 0% to 87% of endocervical adenocarcinoma (ECA) specimens (summarized in Table 1). 1,[3][4][5][6][7][8][9] The goal of this study was to evaluate PAX8 expression by immunohistochemistry (IHC) in endocervix.…”

N-terminal PAX8 polyclonal antibody shows cross-reactivity with N-terminal region of PAX5 and is responsible for reports of PAX8 positivity in malignant lymphomas

“…[3][4][5][6][7] PAX8 has been reported to have a role in diagnosis as a sensitive and specific marker for tumors of renal, Mü llerian or thyroid origin in both primary and metastatic sites. [8][9][10][11] Others have reported PAX8 expression in B-lymphocytes in both normal lymphoid organs and hematological neoplasms as well, 8,10,11 and lymphocytes have been used as an internal positive control for PAX8 immunostaining. 10,12 PAX5 by contrast, regulates B-cell development and influences the balance between immunoglobulin secretion and B-cell proliferation.…”

“…[8][9][10][11] Others have reported PAX8 expression in B-lymphocytes in both normal lymphoid organs and hematological neoplasms as well, 8,10,11 and lymphocytes have been used as an internal positive control for PAX8 immunostaining. 10,12 PAX5 by contrast, regulates B-cell development and influences the balance between immunoglobulin secretion and B-cell proliferation. PAX5 expression is a wellknown immunohistochemical marker for defining B-cell lineage in hematological neoplasms.…”