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HNF-1β as an immunohistochemical marker for distinguishing chromophobe renal cell carcinoma and hybrid oncocytic tumors from renal oncocytoma

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Abstract

The histologic features of renal oncocytoma (RO) are similar to those for the more aggressive chromophobe renal cell carcinoma (ChRCC). To assess immunohistochemical markers of the two, the sensitivity and specificity of cytokeratin 7 (CK7) and C-kit, as well as hepatocyte nuclear factor-1β (HNF-1β), were analyzed. Typical cases of ChRCC and RO at Severance Hospital between July 2014 and July 2018 were selected retrospectively. Among 44 cases, 17 were unanimously compatible with ChRCC, 16 were RO, and 11 cases were indeterminate. Samples from all selected cases were used for immunostaining with antibodies against CK7, C-kit, HNF-1β, and CD10. Immunostaining demonstrated complete loss of HNF-1β expression in 11 out of 17 (64.7%) ChRCC cases and a partial, but significant loss in > 50% of tumor cells in the remaining 6 cases (35.3%). In contrast, HNF-1β expression was preserved in tumor cells of RO cases. Fourteen of 17 ChRCC cases (82.4%) were diffusely positive for CK7, whereas cases of RO were focal positive or negative. C-kit staining did not show a significant difference between ChRCC and RO. Two of five ChRCC cases showing diffuse immunoreactivity for CD10 had poor prognoses of local invasion, distant metastasis, or death. Loss of HNF-1β expression is a useful marker with which to diagnose ChRCC, especially in cases with confusing histologic findings or equivocal CK7 staining. Additionally, CD10 staining in high-grade ChRCC aids in diagnosis and prediction of the clinical prognosis.

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Abbreviations

ChRCC:

chromophobe renal cell carcinoma

RO:

renal oncocytoma

CK7:

cytokeratin 7

HNF-1β:

hepatocyte nuclear factor-1β

PPV:

positive predictive value

NPV:

negative predictive value

CD10:

cluster of differentiation 10

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Funding

This study was supported by the Mid-Career Researcher Program through a grant from the National Research Foundation of Korea (no. 2019R1A2B5B01069934 to N.H.C.) and the Korea Health Technology Research and Development Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (grant no. HI17C1792).

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Authors and Affiliations

  1. Department of Pathology, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea

    Jiyeon An, Cheol Keun Park, Moonsik Kim, Jin Woo Joo & Nam Hoon Cho

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Contributions

NHC was responsible for the conception, design, and financial support of the study. JA, MK, and JWJ collected and processed the data. JA, CKP, MK, JWJ, and NHC evaluated the histological and immunohistochemical findings. JA, CKP, and NHC analyzed the data and interpreted the results. JA and NHC drafted the manuscript. JA, CKP, MK, and NHC revised the manuscript. All authors have agreed to the content of the manuscript, provided revisions as necessary to the manuscript, and provided their final approval of the current version of the submitted manuscript for publication.

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Correspondence to Nam Hoon Cho.

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This study was approved by an institutional ethical board committee (IRB No: 4-2016-1086).

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An, J., Park, C.K., Kim, M. et al. HNF-1β as an immunohistochemical marker for distinguishing chromophobe renal cell carcinoma and hybrid oncocytic tumors from renal oncocytoma. Virchows Arch 478, 459–470 (2021). https://doi.org/10.1007/s00428-020-02912-7

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