The Utility of ERBB4 and RB1 Immunohistochemistry in Distinguishing Chromophobe Renal Cell Carcinoma From Renal Oncocytoma

Tong Sun, Lloyd Hutchinson, Amy G. Zhou, Qingqing Liu, Ediz F. Cosar, Maryann St. Cyr, Nicole Ninteau, Karen Dresser, Liang Cheng, Zhong Jiang, Kristine M. Cornejo

Research output: Contribution to journalArticle

Abstract

Objectives. Differentiating renal oncocytoma (RO) from chromophobe renal cell carcinoma (ChRCC) can occasionally be challenging. We evaluated the expression of RB1 and ERBB4 in RO and ChRCC, and compared the immunohistochemistry (IHC) results to RB1 and ERBB4 gene abnormalities detected by fluorescence in situ hybridization (FISH). Materials and Methods. Fifty-three kidney resections (ChRCC, n=28; RO, n=25) were stained for RB1 and ERBB4 IHC and FISH was performed to evaluate gene copy number analysis. Results. A loss of RB1 staining was identified in 64% (18/28) of ChRCCs, which was not found in any ROs (0/25; P <.001). FISH analysis revealed 36% (10/28) of ChRCCs contained a RB1 hemizygous deletion with a concordance of 56% (10/18) between the IHC and FISH findings. No RB1 gene copy number variations were detected in any of the ROs (0/25; P <.001) and retained expression of RB1 by IHC. ERBB4 showed cytoplasmic/membranous staining in all ROs and ChRCCs. However, 75% (21/28) of ChRCCs also contained nuclear positivity for ERBB4, which was uncommonly seen in ROs (3/25, 12%; P <.001). A hemizygous ERBB4 gene deletion was detected in 46% of ChRCCs (13/28), but none of the ROs (0/25; 0%). Loss of labeling by RB1 or nuclear staining for ERBB4 IHC identified 25 of 28 (89%) of ChRCCs. Conclusion. In summary, the loss of RB1 expression is a highly specific diagnostic biomarker in distinguishing ChRCC from RO. Nuclear ERBB4 expression also appears to be a sensitive diagnostic biomarker for ChRCC, albeit the mechanism is unknown.

Original languageEnglish (US)
JournalInternational Journal of Surgical Pathology
DOIs
StateAccepted/In press - Jan 1 2019

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Renal Cell Carcinoma
Fluorescence In Situ Hybridization
Immunohistochemistry
Gene Dosage
Staining and Labeling
Biomarkers
Gene Deletion
Renal oncocytoma
Kidney
Genes

Keywords

  • chromophobe renal cell carcinoma
  • ERBB4
  • fluorescence in situ hybridization
  • immunohistochemistry
  • RB1
  • renal oncocytoma

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

Cite this

The Utility of ERBB4 and RB1 Immunohistochemistry in Distinguishing Chromophobe Renal Cell Carcinoma From Renal Oncocytoma. / Sun, Tong; Hutchinson, Lloyd; Zhou, Amy G.; Liu, Qingqing; Cosar, Ediz F.; St. Cyr, Maryann; Ninteau, Nicole; Dresser, Karen; Cheng, Liang; Jiang, Zhong; Cornejo, Kristine M.

In: International Journal of Surgical Pathology, 01.01.2019.

Research output: Contribution to journalArticle

Sun, Tong ; Hutchinson, Lloyd ; Zhou, Amy G. ; Liu, Qingqing ; Cosar, Ediz F. ; St. Cyr, Maryann ; Ninteau, Nicole ; Dresser, Karen ; Cheng, Liang ; Jiang, Zhong ; Cornejo, Kristine M. / The Utility of ERBB4 and RB1 Immunohistochemistry in Distinguishing Chromophobe Renal Cell Carcinoma From Renal Oncocytoma. In: International Journal of Surgical Pathology. 2019.
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abstract = "Objectives. Differentiating renal oncocytoma (RO) from chromophobe renal cell carcinoma (ChRCC) can occasionally be challenging. We evaluated the expression of RB1 and ERBB4 in RO and ChRCC, and compared the immunohistochemistry (IHC) results to RB1 and ERBB4 gene abnormalities detected by fluorescence in situ hybridization (FISH). Materials and Methods. Fifty-three kidney resections (ChRCC, n=28; RO, n=25) were stained for RB1 and ERBB4 IHC and FISH was performed to evaluate gene copy number analysis. Results. A loss of RB1 staining was identified in 64{\%} (18/28) of ChRCCs, which was not found in any ROs (0/25; P <.001). FISH analysis revealed 36{\%} (10/28) of ChRCCs contained a RB1 hemizygous deletion with a concordance of 56{\%} (10/18) between the IHC and FISH findings. No RB1 gene copy number variations were detected in any of the ROs (0/25; P <.001) and retained expression of RB1 by IHC. ERBB4 showed cytoplasmic/membranous staining in all ROs and ChRCCs. However, 75{\%} (21/28) of ChRCCs also contained nuclear positivity for ERBB4, which was uncommonly seen in ROs (3/25, 12{\%}; P <.001). A hemizygous ERBB4 gene deletion was detected in 46{\%} of ChRCCs (13/28), but none of the ROs (0/25; 0{\%}). Loss of labeling by RB1 or nuclear staining for ERBB4 IHC identified 25 of 28 (89{\%}) of ChRCCs. Conclusion. In summary, the loss of RB1 expression is a highly specific diagnostic biomarker in distinguishing ChRCC from RO. Nuclear ERBB4 expression also appears to be a sensitive diagnostic biomarker for ChRCC, albeit the mechanism is unknown.",
keywords = "chromophobe renal cell carcinoma, ERBB4, fluorescence in situ hybridization, immunohistochemistry, RB1, renal oncocytoma",
author = "Tong Sun and Lloyd Hutchinson and Zhou, {Amy G.} and Qingqing Liu and Cosar, {Ediz F.} and {St. Cyr}, Maryann and Nicole Ninteau and Karen Dresser and Liang Cheng and Zhong Jiang and Cornejo, {Kristine M.}",
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T1 - The Utility of ERBB4 and RB1 Immunohistochemistry in Distinguishing Chromophobe Renal Cell Carcinoma From Renal Oncocytoma

AU - Sun, Tong

AU - Hutchinson, Lloyd

AU - Zhou, Amy G.

AU - Liu, Qingqing

AU - Cosar, Ediz F.

AU - St. Cyr, Maryann

AU - Ninteau, Nicole

AU - Dresser, Karen

AU - Cheng, Liang

AU - Jiang, Zhong

AU - Cornejo, Kristine M.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Objectives. Differentiating renal oncocytoma (RO) from chromophobe renal cell carcinoma (ChRCC) can occasionally be challenging. We evaluated the expression of RB1 and ERBB4 in RO and ChRCC, and compared the immunohistochemistry (IHC) results to RB1 and ERBB4 gene abnormalities detected by fluorescence in situ hybridization (FISH). Materials and Methods. Fifty-three kidney resections (ChRCC, n=28; RO, n=25) were stained for RB1 and ERBB4 IHC and FISH was performed to evaluate gene copy number analysis. Results. A loss of RB1 staining was identified in 64% (18/28) of ChRCCs, which was not found in any ROs (0/25; P <.001). FISH analysis revealed 36% (10/28) of ChRCCs contained a RB1 hemizygous deletion with a concordance of 56% (10/18) between the IHC and FISH findings. No RB1 gene copy number variations were detected in any of the ROs (0/25; P <.001) and retained expression of RB1 by IHC. ERBB4 showed cytoplasmic/membranous staining in all ROs and ChRCCs. However, 75% (21/28) of ChRCCs also contained nuclear positivity for ERBB4, which was uncommonly seen in ROs (3/25, 12%; P <.001). A hemizygous ERBB4 gene deletion was detected in 46% of ChRCCs (13/28), but none of the ROs (0/25; 0%). Loss of labeling by RB1 or nuclear staining for ERBB4 IHC identified 25 of 28 (89%) of ChRCCs. Conclusion. In summary, the loss of RB1 expression is a highly specific diagnostic biomarker in distinguishing ChRCC from RO. Nuclear ERBB4 expression also appears to be a sensitive diagnostic biomarker for ChRCC, albeit the mechanism is unknown.

AB - Objectives. Differentiating renal oncocytoma (RO) from chromophobe renal cell carcinoma (ChRCC) can occasionally be challenging. We evaluated the expression of RB1 and ERBB4 in RO and ChRCC, and compared the immunohistochemistry (IHC) results to RB1 and ERBB4 gene abnormalities detected by fluorescence in situ hybridization (FISH). Materials and Methods. Fifty-three kidney resections (ChRCC, n=28; RO, n=25) were stained for RB1 and ERBB4 IHC and FISH was performed to evaluate gene copy number analysis. Results. A loss of RB1 staining was identified in 64% (18/28) of ChRCCs, which was not found in any ROs (0/25; P <.001). FISH analysis revealed 36% (10/28) of ChRCCs contained a RB1 hemizygous deletion with a concordance of 56% (10/18) between the IHC and FISH findings. No RB1 gene copy number variations were detected in any of the ROs (0/25; P <.001) and retained expression of RB1 by IHC. ERBB4 showed cytoplasmic/membranous staining in all ROs and ChRCCs. However, 75% (21/28) of ChRCCs also contained nuclear positivity for ERBB4, which was uncommonly seen in ROs (3/25, 12%; P <.001). A hemizygous ERBB4 gene deletion was detected in 46% of ChRCCs (13/28), but none of the ROs (0/25; 0%). Loss of labeling by RB1 or nuclear staining for ERBB4 IHC identified 25 of 28 (89%) of ChRCCs. Conclusion. In summary, the loss of RB1 expression is a highly specific diagnostic biomarker in distinguishing ChRCC from RO. Nuclear ERBB4 expression also appears to be a sensitive diagnostic biomarker for ChRCC, albeit the mechanism is unknown.

KW - chromophobe renal cell carcinoma

KW - ERBB4

KW - fluorescence in situ hybridization

KW - immunohistochemistry

KW - RB1

KW - renal oncocytoma

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