Current challenges for HER2 testing in diagnostic pathology: state of the art and controversial issues

HER2 overexpression and anti-HER2 agents represent probably the best story of success of individualized therapy in breast cancer. Due to the important therapeutic implications, the issue under the spotlight has been, since ever, the correct identification of true HER2 positivity on tissue specimens....

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Main Authors: Anna eSapino, Margherita eGoia, Daniele eRecupero, Caterina eMarchio
Format: Article
Language:English
Published: Frontiers Media S.A. 2013-05-01
Series:Frontiers in Oncology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fonc.2013.00129/full
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author Anna eSapino
Margherita eGoia
Daniele eRecupero
Caterina eMarchio
author_facet Anna eSapino
Margherita eGoia
Daniele eRecupero
Caterina eMarchio
author_sort Anna eSapino
collection DOAJ
description HER2 overexpression and anti-HER2 agents represent probably the best story of success of individualized therapy in breast cancer. Due to the important therapeutic implications, the issue under the spotlight has been, since ever, the correct identification of true HER2 positivity on tissue specimens. Eligibility to anti-HER2 agents is strictly dependent on the demonstration of HER2 overexpression (by immunohistochemistry) or of HER2 gene amplification by in situ techniques (Fluorescence In Situ Hybridization, FISH), however there are controversial issues involving cases with equivocal HER2 status based on conventional techniques (about 20% of specimens). In terms of HER2 expression a major debate is the presence of full-length and truncated forms of the protein and controversial clinical data have been reported on the therapeutic implications of these HER2 fragments. In terms of HER2 gene assessment, the occurrence of amplification of the chromosome 17 centromeric region (CEP17) has been proven responsible for misleading HER2 FISH results, precluding anti-HER2 based therapy to some patients. Finally HER2 activating mutations have been recently described as a biological mechanisms alternative to HER2 gene amplification. In this review we will focus on the controversies that pathologists and oncologists routinely face in the attempt to design the most tailored treatment for breast cancer patients. We will focus on the HER2 gene and on the protein, both at technical and interpretational levels.
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spelling doaj.art-d74aa0f521484133a36e1229371af1182022-12-21T20:48:13ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2013-05-01310.3389/fonc.2013.0012952871Current challenges for HER2 testing in diagnostic pathology: state of the art and controversial issuesAnna eSapino0Margherita eGoia1Daniele eRecupero2Caterina eMarchio3University of TurinUniversity of TurinUniversity of TurinUniversity of TurinHER2 overexpression and anti-HER2 agents represent probably the best story of success of individualized therapy in breast cancer. Due to the important therapeutic implications, the issue under the spotlight has been, since ever, the correct identification of true HER2 positivity on tissue specimens. Eligibility to anti-HER2 agents is strictly dependent on the demonstration of HER2 overexpression (by immunohistochemistry) or of HER2 gene amplification by in situ techniques (Fluorescence In Situ Hybridization, FISH), however there are controversial issues involving cases with equivocal HER2 status based on conventional techniques (about 20% of specimens). In terms of HER2 expression a major debate is the presence of full-length and truncated forms of the protein and controversial clinical data have been reported on the therapeutic implications of these HER2 fragments. In terms of HER2 gene assessment, the occurrence of amplification of the chromosome 17 centromeric region (CEP17) has been proven responsible for misleading HER2 FISH results, precluding anti-HER2 based therapy to some patients. Finally HER2 activating mutations have been recently described as a biological mechanisms alternative to HER2 gene amplification. In this review we will focus on the controversies that pathologists and oncologists routinely face in the attempt to design the most tailored treatment for breast cancer patients. We will focus on the HER2 gene and on the protein, both at technical and interpretational levels.http://journal.frontiersin.org/Journal/10.3389/fonc.2013.00129/fulltherapydiagnosistestHER2truncated HER2CEP17 amplification
spellingShingle Anna eSapino
Margherita eGoia
Daniele eRecupero
Caterina eMarchio
Current challenges for HER2 testing in diagnostic pathology: state of the art and controversial issues
Frontiers in Oncology
therapy
diagnosis
test
HER2
truncated HER2
CEP17 amplification
title Current challenges for HER2 testing in diagnostic pathology: state of the art and controversial issues
title_full Current challenges for HER2 testing in diagnostic pathology: state of the art and controversial issues
title_fullStr Current challenges for HER2 testing in diagnostic pathology: state of the art and controversial issues
title_full_unstemmed Current challenges for HER2 testing in diagnostic pathology: state of the art and controversial issues
title_short Current challenges for HER2 testing in diagnostic pathology: state of the art and controversial issues
title_sort current challenges for her2 testing in diagnostic pathology state of the art and controversial issues
topic therapy
diagnosis
test
HER2
truncated HER2
CEP17 amplification
url http://journal.frontiersin.org/Journal/10.3389/fonc.2013.00129/full
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