PAX 8 expression in non-neoplastic tissues, primary tumors, and metastatic tumors: a comprehensive immunohistochemical study

Abstract

PAX 8 is a transcription factor that is essential for embryonic development of the kidney, Mü llerian organs, and thyroid. It may also have a role in tumor development in these organs. The diagnostic utility of PAX 8 has not been comprehensively studied. Formalin-fixed, paraffin-embedded tissue samples for non-neoplastic tissues (n ¼ 1601), primary neoplasms (n ¼ 933), and metastatic neoplasms (n ¼ 496) were subjected to PAX 8 immunostain. In non-neoplastic tissues, PAX 8 was consistently noted in glomerular parietal epithelial cells, renal collecting ductal cells, atrophic renal tubular epithelial cells regardless of nephronic segments, and epithelial cells of the endocervix, endometrium, fallopian tube, seminal vesicle, epidydimis, thyroid, pancreatic islet cells, and lymphoid cells. PAX 8 was not seen in the rest of the tissue samples. In primary neoplasms, PAX 8 was expressed by 194 of 240 (89%) renal cell neoplasms, by 238 of 267 (89%) Mü llerian-type neoplasms, by 65 of 65 (100%) thyroid follicular cell neoplasms, by 8 of 8 (100%) nephrogenic adenomas, and by 17 of 17 (100%) lymphomas. Weak focal staining was noted in 5 of 12 (42%) cases of parathyroid hyperplasia/adenoma and in 6 of 17 (35%) well-differentiated neuroendocrine tumors of the pancreas. PAX 8 was not seen in other neoplasms. In metastatic neoplasms, PAX 8 was expressed by 90 of 102 (88%) metastatic renal cell carcinomas, by 57 of 63 metastatic Mü llerian tumors (90%), and by 6 of 6 metastatic papillary thyroid carcinomas (100%). There was also weak focal staining for 1 of 15 metastatic small cell carcinomas and for 1 of 9 metastatic well-differentiated neuroendocrine carcinomas. PAX 8 was not seen in other metastatic neoplasms. It can be successfully identified in routinely processed tissue samples, and its expression is mostly nuclear. PAX 8 expression in nonneoplastic mature tissues is limited to the organs, the embryonic development of which depends on this transcription factor. This tissue/cell-specific expression is maintained during both neoplastic transformation and metastasis. PAX 8 is a sensitive and specific marker for tumors of renal, Mü llerian, or thyroid origin in both primary and metastatic sites.

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.…”

Deciduoid mesothelioma: report of 21 cases with review of the literature

“…PAX 8 is a marker that is commonly expressed in renal cell carcinomas, [50][51][52] but usually absent in mesotheliomas; 53 therefore, immunostaining for this marker can assist in distinguishing between deciduoid mesothelioma and renal cell carcinomas. In my experience, pleomorphic carcinomas of the lung, in contrast to deciduoid mesotheliomas, do not express calretinin, mesothelin, or WT1, therefore, immunostaining for these markers can assist in discriminating between these two malignancies.…”

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.…”