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Pathology. 2017 Jan;49(1):10-18. doi: 10.1016/j.pathol.2016.05.014. Epub 2016 Dec 4.

Validation of 34betaE12 immunoexpression in clear cell papillary renal cell carcinoma as a sensitive biomarker.

Author information

1
Department of Pathology and Diagnostics, Anatomic Pathology, University and Hospital Trust of Verona, Verona, Italy; Pederzoli Hospital, Anatomic Pathology, Peschiera del Garda, Verona, Italy. Electronic address: guido.martignoni@univr.it.
2
Department of Pathology and Diagnostics, Anatomic Pathology, University and Hospital Trust of Verona, Verona, Italy.
3
Pederzoli Hospital, Anatomic Pathology, Peschiera del Garda, Verona, Italy.
4
Hartmann Institute and HUSLab, University of Helsinki, Department of Pathology, Helsinki, Finland.
5
MRC-Holland, Amsterdam, Netherlands.
6
Histology, Microbiology and Medical Biotechnologies, University of Padua, Padua, Italy.
7
Department of Pathology, Anatomic Pathology, University of Padua, Padua, Italy.
8
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States.
9
Wellington School of Medicine and Health Sciences, Department of Pathology and Molecular Medicine, University of Otago, Wellington, New Zealand.

Abstract

Clear cell papillary renal cell carcinoma (CCPRCC) is a recently recognised neoplasm with a broad spectrum of morphological characteristics, thus representing a challenging differential diagnosis, especially with the low malignant potential multicystic renal cell neoplasms and clear cell renal cell carcinoma. We selected 14 cases of CCPRCC with a wide spectrum of morphological features diagnosed on morphology and CK7 immunoreactivity and analysed them using a panel of immunohistochemical markers, focusing on 34βE12 and related CKs 1,5,10 and 14 and several molecular analyses such as fluorescence in situ hybridisation (FISH), array comparative genomic hybridisation (aCGH), VHL methylation, VHL and TCEB1 sequencing and multiplex ligation-dependent probe amplification (MLPA). Twelve of 13 (92%) CCPRCC tumours were positive for 34βE12. One tumour without 3p alteration by FISH revealed VHL mutation and 3p deletion at aCGH; thus, it was re-classified as clear cell RCC. We concluded that: (1) immunohistochemical expression of CK7 is necessary for diagnostic purposes, but may not be sufficient to identify CCPRCC, while 34βE12, in part due to the presence of CK14 antigen expression, can be extremely useful for the recognition of this tumour; and (2) further molecular analysis of chromosome 3p should be considered to support of CCPRCC diagnosis, when FISH analysis does not evidence the common loss of chromosome 3p.

KEYWORDS:

34βE12; CK14 antigen expression; CK7 immunoreactivity; Clear cell papillary renal cell carcinoma; FISH analysis; VHL mutation; aCGH; biomarker; chromosome 3p deletion

PMID:
27923499
DOI:
10.1016/j.pathol.2016.05.014
[Indexed for MEDLINE]

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