Expression of PAX8 in normal and neoplastic renal tissues: an immunohistochemical study

Abstract

Cell-lineage-specific transcription factors are a group of regulatory proteins expressed in embryonic, differentiated, or neoplastic cells of the same lineage and represent a valuable repertoire of tissue-specific markers for the diagnosis of human tumors. Together with PAX2, PAX8 is a nephric-lineage transcription factor and is required for the establishment of renal-lineage cells and the formation of the kidney. In contrast to PAX2, little is known about the expression of PAX8 in adult kidney and renal tumors. In this study, we used immunohistochemistry to investigate the expression of PAX8 in adult human kidney and renal epithelial tumors. We report here that PAX8 was detected in renal epithelial cells in all segments of renal tubules from the proximal tubules to the renal papillae and in the parietal cells of Bowman's capsule in the adult kidney. PAX8 was also present in 98% of clear cell renal cell carcinomas (RCCs), 90% of papillary RCCs, and 95% of oncocytomas, similar to PAX2. In addition, PAX8 was found in 82% of chromophobe RCCs, 71% of sarcomatoid components of RCCs, and 100% (2/2) of renal medullary carcinomas. Overall, PAX8 was detected in 85% of metastatic renal tumors. Interestingly, expression of PAX8 was noted in some urothelial cells in the renal pelvis and ureters and B23% of urothelial carcinomas of the renal pelvis, but not in the urothelium or urothelial carcinomas of the urinary bladder; this probably underlines the different embryonic origins of urothelial cells in the upper and lower urinary tracts. As shown in this study, PAX8 is widely expressed in normal and neoplastic renal tissues. PAX8 may be a useful additional marker for renal epithelial tumors; however, its specificity and sensitivity await further investigation.

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

“…Although the staining is focal and involves only some of the tested tissue samples, our findings do confirm the original observations by Tong et al 16 and Long et al, 28 respectively. This pattern of expression is surprising as PAX 8 has not been known to control the organogenesis of parathyroid or pancreatic islets.…”

“…27 The significance of this neoexpression is not clear, but it may be related to a known function of PAX 8 to promote the proliferation and repair of renal tubular cells. Although Tong et al 16 described focal staining of renal pelvic urothelial cells, we have not observed PAX 8 expression in 27 samples of the urothelium from various locations.…”

“…Previous studies have shown that PAX 8 was noted in most renal cell carcinomas (89%), 16 most ovarian carcinomas (64-100%), [18][19][20] and in all nephrogenic adenomas, 17 but staining features in relation to pattern, extent, histological types, or differentiation levels were not detailed.…”

“…Tong et al 16,17 and Bowen et al 18 in studies of a limited number of cases showed PAX 8 expression in the nuclei of thyroid follicular cells, renal tubular epithelial cells, and epithelial cells of the fallopian tubes, endometrial glands, epididymis, vas deferens, and seminal vesicles, but not in epithelial cells of the breast, lung, esophagus, stomach, colon, pancreas, and mesothelium. Our comprehensive study corroborates and expands these observations.…”

“…A few limited studies have identified PAX 8 in neoplasms of the organs the embryogenesis of which is under control of this transcription factor, including thyroid follicular neoplasm, [12][13][14][15] renal cell carcinoma, 11,16 nephrogenic adenoma, 17 and ovarian carcinoma. [18][19][20] Confirmation of PAX 8 as a sensitive marker for these tumor types is required.…”