The Utility of Pax-2 and Renal Cell Carcinoma Marker Immunohistochemistry in Distinguishing Papillary Renal Cell Carcinoma From Nonrenal Cell Neoplasms With Papillary Features

Abstract

PAX-2, a homeogene expressed during kidney development, has been studied as a marker of renal origin in both primary and metastatic clear cell renal cell carcinoma (RCC), but not in papillary neoplasms or in comparison with RCC marker (RCCma). We studied immunohistochemical expression of PAX-2 and RCCma in 24 papillary RCC (PRCC) and 66 nonrenal cell papillary neoplasms (NRCPN) from a variety of organs. Of the PRCC, 16/24 (67%) were positive for PAX-2; 23/24 (96%) were positive for RCCma. Of the NRCPN, 9/66 (14%) is positive for PAX-2 [4/10 (40%) ovarian papillary serous carcinomas, 5/9 (56%) uterine papillary serous carcinomas]; RCCma was positive in 28/66 (42%), including 9/9 (100%) papillary thyroid carcinomas, 8/10 (80%) ovarian papillary serous carcinomas, 4/9 (44%) uterine papillary serous carcinomas, 1/10 (10%) papillary urothelial carcinomas, 1/2 (50%) intraductal papillary mucinous carcinomas of the pancreas, 3/3 (100%) choroid plexus papillomas, 1/1 (100%) pituitary adenoma with papillary features, and 1/2 (50%) lung adenocarcinomas with papillary features. The sensitivity of PAX-2+/RCCma+ immunophenotype for PRCC was 58% with a specificity of 54%. There is significant overlap between the expressions of these markers in PRCC and NRCPN; however, the positivity of RCCma and/or PAX-2 is 100% sensitive for PRCC and may prove useful in the initial work up of metastases of unknown primary. PAX-2 and RCCma immunohistochemistry should be interpreted with caution in papillary neoplasms, with particular attention to the possibility of ovarian and uterine papillary serous carcinomas, which can express both PAX-2 and RCCma.

Application of immunohistochemistry in the diagnosis of epithelioid mesothelioma: a review and update

“…Among tumors, PAX 2 has been reported to be expressed in the epithelial neoplasms of these organs, the embryogenesis of which is under the control of this transcription factor. These include all subtypes of renal cell carcinomas [158][159][160] and serous carcinomas of the ovary [160][161][162]. The percentage of PAX 2 positivity reported in metastatic clear cell renal cell carcinomas in different series has ranged from 49% to 85% [153,160,163] and, for serous carcinomas, 27% to 67% of the cases investigated [160][161][162].…”

Value of PAX8, PAX2, claudin-4, and h-caldesmon immunostaining in distinguishing peritoneal epithelioid mesotheliomas from serous carcinomas

“…39 In a combined review of 132 cases of primary and 53 metastatic ovarian serous carcinomas from six published studies, 63 (48%) and 23 (43%), respectively, were reported to be PAX2 positive. 14,31,[35][36][37][38] In addition, 2 (29%) of the 7 primary peritoneal serous carcinomas that have been investigated for PAX2 expression were positive for this marker. 31 That only 8 (53%) of the 15 primary and 17 (57%) of the 30 metastatic ovarian serous carcinomas in the present investigation were PAX2 positive indicates that the sensitivity of this marker for serous carcinomas is lower than that of PAX8.…”

“…33,34 PAX2 null mice of both sexes completely lack the entire genital tract. 33 Among ovarian carcinomas, PAX2 expression has been reported to be often expressed in serous (27-100%), 14,[35][36][37][38] endometrioid (40%), 38 and clear cell (43%) carcinomas. 39 In a combined review of 132 cases of primary and 53 metastatic ovarian serous carcinomas from six published studies, 63 (48%) and 23 (43%), respectively, were reported to be PAX2 positive.…”

PAX2 and PAX8 Reliably Distinguishes Ovarian Serous Tumors From Mucinous Tumors

“…[17][18][19] Several studies, each of which is devoted exclusively to either PAX2 or PAX8, have documented their expression in ovarian tumors. 11,[20][21][22][23] These studies further suggest a similar pattern of expression for PAX2 and PAX8 in these ovarian tumors. Nevertheless, a comprehensive direct combination of these 2 markers is not available, leaving several pertinent diagnostic issues unresolved, such as their comparative diagnostic sensitivity and specificity in ovarian serous tumors and ovarian mucinous tumors.…”