PAX8 (+)/p63 (-) Immunostaining pattern in renal collecting duct carcinoma (CDC)

A useful immunoprofile in the differential diagnosis of CDC versus urothelial carcinoma of upper urinary tract

Roula Albadine, Luciana Schultz, Peter B Illei, Dilek Ertoy, Jessica Hicks, Rajni Sharma, Jonathan Ira Epstein, George J. Netto

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Collecting duct carcinoma (CDC) is a relatively rare but aggressive type of renal malignancy with variable morphologic features. One of the World Health Organization diagnostic criteria for CDC is the exclusion of urothelial carcinoma of renal pelvis from the differential diagnosis. PAX8 is a novel lineage restricted transcription factor expressed in renal tubules. We investigated the expression pattern of PAX8 in CDC and its utility, in combination with p63, in resolving the differential diagnosis of CDC versus upper tract urothelial carcinoma (UUC). DESIGN: Archival tissues from 21 CDC and 34 UUC were retrieved from our institutional files. Immunohistochemistry for PAX8 and p63 were performed on routine and tissue microarray sections using standard immunohistochemistry protocol. Intensity of nuclear staining was evaluated for each marker and assigned an incremental 0, 1+, 2+, and 3+ score. Extent of staining was categorized as focal (75%). RESULTS: CDC: All 21 (100%) CDC were positive for PAX8. Intensity of expression was moderate to strong (2+/3+) in 19 cases (90%). Extent of staining was diffuse in 13 of 21 tumors. The p63 was positive in 3 of 21 (14%) CDC cases (PAX8+/p63+). UUC: The 34 UUC included 5 pT1, 4 pT2, and 25 pT3/pT4 tumors. Thirty-one of 34 (91.2%) UUC were negative for PAX8, whereas 33 of 34 (97%) were p63 positive. Staining intensity was moderate in 15 cases (44%), of which 12 were nonfocal or diffuse. The unique p63-negative UUC was a pT1 tumor that was also negative for PAX8 (PAX8-/p63-). CONCLUSIONS: We propose the use of the combination of PAX8 and p63 in the diagnosis of poorly differentiated renal sinus epithelial neoplasms where the differential diagnosis includes CDC versus UUC. The immunoprofile of PAX8+/p63-supports the diagnosis of CDC with a sensitivity of 85.7% and a specificity of 100%. In contrast, a (PAX8-/p63+) profile supports the diagnosis of UUC with a sensitivity of 88.2% and a specificity of 100%. The inverse PAX8/p63 expression seen in CDC and UUC supports a renal tubular rather than an urothelial differentiation in CDC given the nephric lineage restriction of PAX8.

Original languageEnglish (US)
Pages (from-to)965-969
Number of pages5
JournalAmerican Journal of Surgical Pathology
Volume34
Issue number7
DOIs
StatePublished - Jul 2010

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Urinary Tract
Renal Cell Carcinoma
Differential Diagnosis
Carcinoma
Kidney
Staining and Labeling
Neoplasms
Immunohistochemistry
Kidney Pelvis
Glandular and Epithelial Neoplasms
Transcription Factors

Keywords

  • collecting duct carcinoma
  • p63
  • PAX8
  • urothelial carcinoma

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine
  • Surgery

Cite this

PAX8 (+)/p63 (-) Immunostaining pattern in renal collecting duct carcinoma (CDC) : A useful immunoprofile in the differential diagnosis of CDC versus urothelial carcinoma of upper urinary tract. / Albadine, Roula; Schultz, Luciana; Illei, Peter B; Ertoy, Dilek; Hicks, Jessica; Sharma, Rajni; Epstein, Jonathan Ira; Netto, George J.

In: American Journal of Surgical Pathology, Vol. 34, No. 7, 07.2010, p. 965-969.

Research output: Contribution to journalArticle

@article{fefb0e7f8fd14fdba97ab530c91a0498,
title = "PAX8 (+)/p63 (-) Immunostaining pattern in renal collecting duct carcinoma (CDC): A useful immunoprofile in the differential diagnosis of CDC versus urothelial carcinoma of upper urinary tract",
abstract = "BACKGROUND: Collecting duct carcinoma (CDC) is a relatively rare but aggressive type of renal malignancy with variable morphologic features. One of the World Health Organization diagnostic criteria for CDC is the exclusion of urothelial carcinoma of renal pelvis from the differential diagnosis. PAX8 is a novel lineage restricted transcription factor expressed in renal tubules. We investigated the expression pattern of PAX8 in CDC and its utility, in combination with p63, in resolving the differential diagnosis of CDC versus upper tract urothelial carcinoma (UUC). DESIGN: Archival tissues from 21 CDC and 34 UUC were retrieved from our institutional files. Immunohistochemistry for PAX8 and p63 were performed on routine and tissue microarray sections using standard immunohistochemistry protocol. Intensity of nuclear staining was evaluated for each marker and assigned an incremental 0, 1+, 2+, and 3+ score. Extent of staining was categorized as focal (75{\%}). RESULTS: CDC: All 21 (100{\%}) CDC were positive for PAX8. Intensity of expression was moderate to strong (2+/3+) in 19 cases (90{\%}). Extent of staining was diffuse in 13 of 21 tumors. The p63 was positive in 3 of 21 (14{\%}) CDC cases (PAX8+/p63+). UUC: The 34 UUC included 5 pT1, 4 pT2, and 25 pT3/pT4 tumors. Thirty-one of 34 (91.2{\%}) UUC were negative for PAX8, whereas 33 of 34 (97{\%}) were p63 positive. Staining intensity was moderate in 15 cases (44{\%}), of which 12 were nonfocal or diffuse. The unique p63-negative UUC was a pT1 tumor that was also negative for PAX8 (PAX8-/p63-). CONCLUSIONS: We propose the use of the combination of PAX8 and p63 in the diagnosis of poorly differentiated renal sinus epithelial neoplasms where the differential diagnosis includes CDC versus UUC. The immunoprofile of PAX8+/p63-supports the diagnosis of CDC with a sensitivity of 85.7{\%} and a specificity of 100{\%}. In contrast, a (PAX8-/p63+) profile supports the diagnosis of UUC with a sensitivity of 88.2{\%} and a specificity of 100{\%}. The inverse PAX8/p63 expression seen in CDC and UUC supports a renal tubular rather than an urothelial differentiation in CDC given the nephric lineage restriction of PAX8.",
keywords = "collecting duct carcinoma, p63, PAX8, urothelial carcinoma",
author = "Roula Albadine and Luciana Schultz and Illei, {Peter B} and Dilek Ertoy and Jessica Hicks and Rajni Sharma and Epstein, {Jonathan Ira} and Netto, {George J.}",
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language = "English (US)",
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pages = "965--969",
journal = "American Journal of Surgical Pathology",
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T1 - PAX8 (+)/p63 (-) Immunostaining pattern in renal collecting duct carcinoma (CDC)

T2 - A useful immunoprofile in the differential diagnosis of CDC versus urothelial carcinoma of upper urinary tract

AU - Albadine, Roula

AU - Schultz, Luciana

AU - Illei, Peter B

AU - Ertoy, Dilek

AU - Hicks, Jessica

AU - Sharma, Rajni

AU - Epstein, Jonathan Ira

AU - Netto, George J.

PY - 2010/7

Y1 - 2010/7

N2 - BACKGROUND: Collecting duct carcinoma (CDC) is a relatively rare but aggressive type of renal malignancy with variable morphologic features. One of the World Health Organization diagnostic criteria for CDC is the exclusion of urothelial carcinoma of renal pelvis from the differential diagnosis. PAX8 is a novel lineage restricted transcription factor expressed in renal tubules. We investigated the expression pattern of PAX8 in CDC and its utility, in combination with p63, in resolving the differential diagnosis of CDC versus upper tract urothelial carcinoma (UUC). DESIGN: Archival tissues from 21 CDC and 34 UUC were retrieved from our institutional files. Immunohistochemistry for PAX8 and p63 were performed on routine and tissue microarray sections using standard immunohistochemistry protocol. Intensity of nuclear staining was evaluated for each marker and assigned an incremental 0, 1+, 2+, and 3+ score. Extent of staining was categorized as focal (75%). RESULTS: CDC: All 21 (100%) CDC were positive for PAX8. Intensity of expression was moderate to strong (2+/3+) in 19 cases (90%). Extent of staining was diffuse in 13 of 21 tumors. The p63 was positive in 3 of 21 (14%) CDC cases (PAX8+/p63+). UUC: The 34 UUC included 5 pT1, 4 pT2, and 25 pT3/pT4 tumors. Thirty-one of 34 (91.2%) UUC were negative for PAX8, whereas 33 of 34 (97%) were p63 positive. Staining intensity was moderate in 15 cases (44%), of which 12 were nonfocal or diffuse. The unique p63-negative UUC was a pT1 tumor that was also negative for PAX8 (PAX8-/p63-). CONCLUSIONS: We propose the use of the combination of PAX8 and p63 in the diagnosis of poorly differentiated renal sinus epithelial neoplasms where the differential diagnosis includes CDC versus UUC. The immunoprofile of PAX8+/p63-supports the diagnosis of CDC with a sensitivity of 85.7% and a specificity of 100%. In contrast, a (PAX8-/p63+) profile supports the diagnosis of UUC with a sensitivity of 88.2% and a specificity of 100%. The inverse PAX8/p63 expression seen in CDC and UUC supports a renal tubular rather than an urothelial differentiation in CDC given the nephric lineage restriction of PAX8.

AB - BACKGROUND: Collecting duct carcinoma (CDC) is a relatively rare but aggressive type of renal malignancy with variable morphologic features. One of the World Health Organization diagnostic criteria for CDC is the exclusion of urothelial carcinoma of renal pelvis from the differential diagnosis. PAX8 is a novel lineage restricted transcription factor expressed in renal tubules. We investigated the expression pattern of PAX8 in CDC and its utility, in combination with p63, in resolving the differential diagnosis of CDC versus upper tract urothelial carcinoma (UUC). DESIGN: Archival tissues from 21 CDC and 34 UUC were retrieved from our institutional files. Immunohistochemistry for PAX8 and p63 were performed on routine and tissue microarray sections using standard immunohistochemistry protocol. Intensity of nuclear staining was evaluated for each marker and assigned an incremental 0, 1+, 2+, and 3+ score. Extent of staining was categorized as focal (75%). RESULTS: CDC: All 21 (100%) CDC were positive for PAX8. Intensity of expression was moderate to strong (2+/3+) in 19 cases (90%). Extent of staining was diffuse in 13 of 21 tumors. The p63 was positive in 3 of 21 (14%) CDC cases (PAX8+/p63+). UUC: The 34 UUC included 5 pT1, 4 pT2, and 25 pT3/pT4 tumors. Thirty-one of 34 (91.2%) UUC were negative for PAX8, whereas 33 of 34 (97%) were p63 positive. Staining intensity was moderate in 15 cases (44%), of which 12 were nonfocal or diffuse. The unique p63-negative UUC was a pT1 tumor that was also negative for PAX8 (PAX8-/p63-). CONCLUSIONS: We propose the use of the combination of PAX8 and p63 in the diagnosis of poorly differentiated renal sinus epithelial neoplasms where the differential diagnosis includes CDC versus UUC. The immunoprofile of PAX8+/p63-supports the diagnosis of CDC with a sensitivity of 85.7% and a specificity of 100%. In contrast, a (PAX8-/p63+) profile supports the diagnosis of UUC with a sensitivity of 88.2% and a specificity of 100%. The inverse PAX8/p63 expression seen in CDC and UUC supports a renal tubular rather than an urothelial differentiation in CDC given the nephric lineage restriction of PAX8.

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KW - p63

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