HER3 Expression Is a Marker of Tumor Progression in Premalignant Lesions of the Gastroesophageal Junction.
Overexpression of receptor tyrosine kinases (RTK), including members of the HER family, has prognostic and therapeutic significance in invasive esophagogastric carcinoma. RTK expression in premalignant gastroesophageal lesions has not been extensively explored. Formalin-fixed paraffin-embedded tissu...
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doaj-39dd41e1575843adacf24393380371122020-11-25T02:10:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01118e016178110.1371/journal.pone.0161781HER3 Expression Is a Marker of Tumor Progression in Premalignant Lesions of the Gastroesophageal Junction.Brett L EckerLaura TaylorPaul J ZhangEmma E FurthGregory G GinsbergMatthew T McMillanJashodeep DattaBrian J CzernieckiRobert E RosesOverexpression of receptor tyrosine kinases (RTK), including members of the HER family, has prognostic and therapeutic significance in invasive esophagogastric carcinoma. RTK expression in premalignant gastroesophageal lesions has not been extensively explored. Formalin-fixed paraffin-embedded tissue samples of esophageal biopsy specimens from 73 patients with Barrett's esophagus with either low-grade dysplasia (LGD) (n = 32) or high-grade dysplasia (HGD) (n = 59) were analyzed for HER1, HER2, HER3 and CMET expression by immunohistochemistry (IHC). Immunophenotype was correlated with histologic and clinical features. High-grade dysplasia (HGD) was associated with overexpression of HER1 (20.7% vs. 3.1%, p = 0.023), HER2 (5.3% vs. 0.0%, p = 0.187) and HER3 (47.4% vs. 9.4%, p<0.001) compared to low-grade dysplasia (LGD). There was a significant association of HER2 (20.0% vs. 2.1%, p = 0.022) and HER3 (80.0% vs. 40.4%, p = 0.023) overexpression in HGD lesions associated with foci of invasive carcinoma compared to those without invasive foci. Overexpression of CMET was observed in 42.9% of specimens, was increasingly observed with HGD compared to LGD (58.3% vs. 36.7%, p = 0.200), and was most often co-expressed with HER3 (62.5% of HER3-positive specimens vs. 38.2% of HER3-negative specimens, p = 0.212). In summary, HER3 is frequently overexpressed in high-grade dysplastic lesions of the gastroesophageal junction and may be a marker of invasive progression. These data provide rationale for targeting HER2 and HER3 pathways in an early disease setting to prevent disease progression.http://europepmc.org/articles/PMC4999185?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Brett L Ecker Laura Taylor Paul J Zhang Emma E Furth Gregory G Ginsberg Matthew T McMillan Jashodeep Datta Brian J Czerniecki Robert E Roses |
spellingShingle |
Brett L Ecker Laura Taylor Paul J Zhang Emma E Furth Gregory G Ginsberg Matthew T McMillan Jashodeep Datta Brian J Czerniecki Robert E Roses HER3 Expression Is a Marker of Tumor Progression in Premalignant Lesions of the Gastroesophageal Junction. PLoS ONE |
author_facet |
Brett L Ecker Laura Taylor Paul J Zhang Emma E Furth Gregory G Ginsberg Matthew T McMillan Jashodeep Datta Brian J Czerniecki Robert E Roses |
author_sort |
Brett L Ecker |
title |
HER3 Expression Is a Marker of Tumor Progression in Premalignant Lesions of the Gastroesophageal Junction. |
title_short |
HER3 Expression Is a Marker of Tumor Progression in Premalignant Lesions of the Gastroesophageal Junction. |
title_full |
HER3 Expression Is a Marker of Tumor Progression in Premalignant Lesions of the Gastroesophageal Junction. |
title_fullStr |
HER3 Expression Is a Marker of Tumor Progression in Premalignant Lesions of the Gastroesophageal Junction. |
title_full_unstemmed |
HER3 Expression Is a Marker of Tumor Progression in Premalignant Lesions of the Gastroesophageal Junction. |
title_sort |
her3 expression is a marker of tumor progression in premalignant lesions of the gastroesophageal junction. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2016-01-01 |
description |
Overexpression of receptor tyrosine kinases (RTK), including members of the HER family, has prognostic and therapeutic significance in invasive esophagogastric carcinoma. RTK expression in premalignant gastroesophageal lesions has not been extensively explored. Formalin-fixed paraffin-embedded tissue samples of esophageal biopsy specimens from 73 patients with Barrett's esophagus with either low-grade dysplasia (LGD) (n = 32) or high-grade dysplasia (HGD) (n = 59) were analyzed for HER1, HER2, HER3 and CMET expression by immunohistochemistry (IHC). Immunophenotype was correlated with histologic and clinical features. High-grade dysplasia (HGD) was associated with overexpression of HER1 (20.7% vs. 3.1%, p = 0.023), HER2 (5.3% vs. 0.0%, p = 0.187) and HER3 (47.4% vs. 9.4%, p<0.001) compared to low-grade dysplasia (LGD). There was a significant association of HER2 (20.0% vs. 2.1%, p = 0.022) and HER3 (80.0% vs. 40.4%, p = 0.023) overexpression in HGD lesions associated with foci of invasive carcinoma compared to those without invasive foci. Overexpression of CMET was observed in 42.9% of specimens, was increasingly observed with HGD compared to LGD (58.3% vs. 36.7%, p = 0.200), and was most often co-expressed with HER3 (62.5% of HER3-positive specimens vs. 38.2% of HER3-negative specimens, p = 0.212). In summary, HER3 is frequently overexpressed in high-grade dysplastic lesions of the gastroesophageal junction and may be a marker of invasive progression. These data provide rationale for targeting HER2 and HER3 pathways in an early disease setting to prevent disease progression. |
url |
http://europepmc.org/articles/PMC4999185?pdf=render |
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