Expression of aquaporins and PAX-2 compared to CD10 and cytokeratin 7 in renal neoplasms: a tissue microarray study

Mazal, Peter R.; Stichenwirth, Martin; Koller, Antje; Blach, Sabine; Haitel, Andrea; Susani, Martin

doi:10.1038/modpathol.3800320

Cited by 124 publications

(88 citation statements)

References 19 publications

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“…23,24,36 We show here that 98% of clear cell RCCs, 90% of papillary RCCs, and 95% of oncocytomas were positive for PAX8, frequencies which are similar or better than for PAX2. PAX8 was also detected in 85% of metastatic RCCs in this study.…”

Section: Pax8 Expression In Normal and Neoplastic Renal Tissues G-x Tmentioning

confidence: 90%

“…[1][2][3][4][5][6] PAX2 is the first renal-specific transcription factor whose diagnostic application in renal epithelial tumors has been investigated extensively. [22][23][24]27 The distribution pattern of PAX8 showed in this study indicates that it may be used as a pan-renalepithelial marker, in addition to its functional counterpart PAX2.…”

Section: Pax8 Expression In Normal and Neoplastic Renal Tissues G-x Tmentioning

confidence: 99%

“…20,21 The diagnostic applications of PAX2 have been studied more extensively than PAX8. It has been detected in Wilms tumors, 22 RCCs, 23,24 and nephrogenic adenomas 25,26 and has been used as a diagnostic marker for benign and malignant lesions of renal origin. 27 PAX8 was detected in pediatric Wilms tumors 28 and recently in nephrogenic adenomas; 29 however, there is little information available about its expression in adult normal or neoplastic renal tissues.…”

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

et al. 2009

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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.

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Section: Pax8 Expression In Normal and Neoplastic Renal Tissues G-x Tmentioning

confidence: 90%

Section: Pax8 Expression In Normal and Neoplastic Renal Tissues G-x Tmentioning

confidence: 99%

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

et al. 2009

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“…The urothelium lining the renal pelvis, ureters, urinary bladder, and urethra as well as the glandular cells of the prostate are negative for PAX2. Renal cell carcinoma 12,13 and NA 1,9 are positive for PAX2, whereas prostate adenocarcinoma and urothelial carcinoma are negative. 9 The epithelial cells of the fallopian tube, uterus, cervix, and papillary serous carcinoma of the ovary are positive for PAX2, 14 but these cells rarely appear in urine.…”

Section: Discussionmentioning

confidence: 99%

Nephrogenic adenoma identified on urine cytology using PAX‐2 immunostaining

Herlitz

Tong

Hamele‐Bena

et al. 2007

Diagnostic Cytopathology

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Urine cytology is a sensitive and specific method in detecting urothelial carcinoma of the urinary bladder, particularly the high-grade ones. However, the cytologic features of nonneoplastic lesions of the lower urinary tract, including nephrogenic adenoma, are nonspecific and may cause false positive diagnosis. Recent evidence has demonstrated that nephrogenic adenoma is a true ''nephrogenic'' lesion derived from the exfoliated and implanted renal tubular cells in the urinary tract. This has promoted the use of immunostaining of renal transcription factor PAX2 in tissue biopsies to differentiate nephrogenic adenoma from the common malignant tumors of the lower urinary tract. We report here that PAX2 immunostaining can also be used in urine cytology specimen to identify nephrogenic adenoma. Combination of PAX2 immunostaining and cytologic analysis may increase the accuracy in identifying this benign lesion in urine cytology specimen and therefore reduce unnecessary repeat cystoscopy and biopsy procedures. This may be a cost effective followup method for patients with an established diagnosis of nephrogenic adenoma. Diagn. Cytopathol. 2008;36:47-49. ' 2007 Wiley-Liss, Inc.Key Words: PAX2; nephrogenic adenoma; urine cytology Nephrogenic adenoma (NA) is an uncommon lesion of the urinary tract often associated with renal transplant, anatomic anomaly, or a history of traumatic injury of the urinary tract. 1 It was traditionally considered to be a metaplastic lesion of the urothelium. However, recent evidence has suggested that NA is a truly ''nephrogenic'' lesion derived from exfoliated and implanted renal tubular cells in the urinary tract. 2 The histologic features of NA are well described and the diagnoses in most cases are straightforward. 3-5 Urine cytology is frequently used to evaluate urinary bladder cancer and constitutes a large portion of cytology specimens. However, the cytologic features of NA are less well defined and it contributes to false positive diagnoses in urine cytology. [6][7][8] In addition, NA may coexist with or develop after the treatment of malignant tumors of the urinary tract, thus further complicating the recognition of this benign lesion. Several immunohistochemical markers have been used to assist in the differential diagnosis of NA. Recently, we reported that the renal transcription factor PAX2 is a reliable marker to distinguish NA from common carcinomas of the urinary tract on tissue sections. 9 We report here our experience utilizing PAX2 antibody in a urine cytology specimen for one NA case. Report of a CaseThe patient was a 69-year-old woman with end stage renal disease secondary to diabetes and hypertension who was on a waiting list for kidney transplant. A 3-cm tumor was noted on the right lateral wall of the urinary bladder during the pretransplant evaluation. The patient underwent a partial cystectomy and the tumor was reportedly resected completely. The histological diagnosis was lowgrade papillary urothelial carcinoma, which resulted in her subsequent removal from the tra...

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“…[2][3][4] In addition, AQP1 and ADFP are greatly overexpressed in renal cell carcinomas compared with normal tubules, albeit more so in clear cell carcinomas than in the papillary morphotype. [5][6][7] The diagnostic feature that has given rise to the term clear cell carcinoma is in fact caused by lipid droplet accumulation within the tumor cells, all of which contain copious amounts of ADFP. Cancer cell shedding alone might consequently be expected to elevate urinary AQP1 and ADFP concentrations, but many cells cast off significant numbers of exosomes during their life cycle.…”

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Screening for Kidney Cancer: Is There a Role for Aquaporin-1 and Adipophilin?

Grebe

Erickson²

2010

Mayo Clinic Proceedings

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For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings a .However, the nature of the analyte, urine, and the biology of renal epithelium tilt the balance in favor of these markers. Urine contains very low concentrations of circulating proteins in the absence of renal disease. In addition, neither AQP1 nor ADFP is a secreted protein. Aquaporin-1 is a membrane protein, and ADFP is an intracellular protein associated with lipid droplets. Therefore, AQP1 or ADFP found in urine can be expected to originate from epithelium facing the filtrate side, rather than the blood side, of the nephron. Within the nephron, concentrations are highest in the proximal tubules. Thus, with urine testing, AQP1 and ADFP not only are organ specific for the kidney but also are localized to the structures that give rise to most renal cell carcinomas. [2][3][4] In addition, AQP1 and ADFP are greatly overexpressed in renal cell carcinomas compared with normal tubules, albeit more so in clear cell carcinomas than in the papillary morphotype. [5][6][7] The diagnostic feature that has given rise to the term clear cell carcinoma is in fact caused by lipid droplet accumulation within the tumor cells, all of which contain copious amounts of ADFP. Cancer cell shedding alone might consequently be expected to elevate urinary AQP1 and ADFP concentrations, but many cells cast off significant numbers of exosomes during their life cycle. These 50-to 90-nm diameter vesicles allow cells to selectively shed certain membrane portions, which can serve a role in cell-to-cell nutrient transport, signaling, and even exchange of nucleic acids and pathogens, as well as allowing selective export of lipids, proteins, peptides, cytokines, and various cellular structures and components. 8 Renal cell carcinomas have been found to shed particularly high numbers of exosomes. 9 It seems plausible-and proven in the case of AQP1-that these exosomes contain AQP1 and ADFP.Thus, AQP1 and ADFP in urine might make surprisingly good candidate tumor markers for the main renal Editorial

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Expression of aquaporins and PAX-2 compared to CD10 and cytokeratin 7 in renal neoplasms: a tissue microarray study

Cited by 124 publications

References 19 publications

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

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

Nephrogenic adenoma identified on urine cytology using PAX‐2 immunostaining

Screening for Kidney Cancer: Is There a Role for Aquaporin-1 and Adipophilin?

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