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

Guido Martignoni, Matteo Brunelli, Diego Segala, Enrico Munari, Stefano Gobbo, Luca Cima, Ioana Borze, Tina Wirtanen, Virinder Kaur Sarhadi, Lilit Atanesyan, Suvi Savola, Luisa Barzon, Giulia Masi, Matteo Fassan, John Eble, Tom Bohling, Liang Cheng, Brett Delahunt, Sakari Knuutila

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)10-18
Number of pages9
JournalPathology
Volume49
Issue number1
DOIs
StatePublished - Jan 1 2017

Fingerprint

Renal Cell Carcinoma
Biomarkers
Fluorescence In Situ Hybridization
Comparative Genomic Hybridization
Neoplasms
Chromosomes
Sequence Deletion
Kidney Neoplasms
Multiplex Polymerase Chain Reaction
Methylation
Differential Diagnosis
Antigens

Keywords

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

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medicine(all)

Cite this

Martignoni, G., Brunelli, M., Segala, D., Munari, E., Gobbo, S., Cima, L., ... Knuutila, S. (2017). Validation of 34betaE12 immunoexpression in clear cell papillary renal cell carcinoma as a sensitive biomarker. Pathology, 49(1), 10-18. https://doi.org/10.1016/j.pathol.2016.05.014

Validation of 34betaE12 immunoexpression in clear cell papillary renal cell carcinoma as a sensitive biomarker. / Martignoni, Guido; Brunelli, Matteo; Segala, Diego; Munari, Enrico; Gobbo, Stefano; Cima, Luca; Borze, Ioana; Wirtanen, Tina; Sarhadi, Virinder Kaur; Atanesyan, Lilit; Savola, Suvi; Barzon, Luisa; Masi, Giulia; Fassan, Matteo; Eble, John; Bohling, Tom; Cheng, Liang; Delahunt, Brett; Knuutila, Sakari.

In: Pathology, Vol. 49, No. 1, 01.01.2017, p. 10-18.

Research output: Contribution to journalArticle

Martignoni, G, Brunelli, M, Segala, D, Munari, E, Gobbo, S, Cima, L, Borze, I, Wirtanen, T, Sarhadi, VK, Atanesyan, L, Savola, S, Barzon, L, Masi, G, Fassan, M, Eble, J, Bohling, T, Cheng, L, Delahunt, B & Knuutila, S 2017, 'Validation of 34betaE12 immunoexpression in clear cell papillary renal cell carcinoma as a sensitive biomarker', Pathology, vol. 49, no. 1, pp. 10-18. https://doi.org/10.1016/j.pathol.2016.05.014
Martignoni, Guido ; Brunelli, Matteo ; Segala, Diego ; Munari, Enrico ; Gobbo, Stefano ; Cima, Luca ; Borze, Ioana ; Wirtanen, Tina ; Sarhadi, Virinder Kaur ; Atanesyan, Lilit ; Savola, Suvi ; Barzon, Luisa ; Masi, Giulia ; Fassan, Matteo ; Eble, John ; Bohling, Tom ; Cheng, Liang ; Delahunt, Brett ; Knuutila, Sakari. / Validation of 34betaE12 immunoexpression in clear cell papillary renal cell carcinoma as a sensitive biomarker. In: Pathology. 2017 ; Vol. 49, No. 1. pp. 10-18.
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AU - Brunelli, Matteo

AU - Segala, Diego

AU - Munari, Enrico

AU - Gobbo, Stefano

AU - Cima, Luca

AU - Borze, Ioana

AU - Wirtanen, Tina

AU - Sarhadi, Virinder Kaur

AU - Atanesyan, Lilit

AU - Savola, Suvi

AU - Barzon, Luisa

AU - Masi, Giulia

AU - Fassan, Matteo

AU - Eble, John

AU - Bohling, Tom

AU - Cheng, Liang

AU - Delahunt, Brett

AU - Knuutila, Sakari

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N2 - 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.

AB - 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.

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KW - VHL mutation

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