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. 2014 Nov 19;4(6):838-49.
eCollection 2014.

HER4 is a novel prognostic biomarker in gastrointestinal stromal tumor specifically originated from stomach

Wen-Yi Zhao  1 , Chun Zhuang  2 , Jia Xu  2 , Ming Wang  2 , Zi-Zhen Zhang  2 , Lin Tu  2 , Chao-Jie Wang  2 , Tian-Long Ling  2 , Hui Cao  2 , Zhi-Gang Zhang  3
Affiliations

HER4 is a novel prognostic biomarker in gastrointestinal stromal tumor specifically originated from stomach

Wen-Yi Zhao et al. Am J Cancer Res. .

Abstract

HER family has been implicated in a number of malignant tumors for predicting prognosis and potential targeted therapy purposes, however, the prognostic roles of HER family in GISTs have not been elaborated yet. Our study aims to fully evaluate the prognostic value of HER family in GIST patients and efficacy of imatinib adjuvant therapy. For HER family expression detection, qPCR were used in 33 flesh GIST specimens, and then, 453 GIST samples (405 GISTs with operation only and 48 with imatinib adjuvant therapy after radical surgery) were collected for tissue microarrays construction and immunohistochemistry (IHC). Clinicopathological data were confirmed by pathological diagnosis and clinical recorders, recurrence-free survivals (RFS) were evaluated in 453 GIST patients. With qPCR and IHC performed, EGFR, HER2 and HER4 are focused on examining prognostic value in remainder of our study by high positive expression rates in GISTs. In high-risk GISTs with or without imatinib adjuvant therapy, EGFR negative expression are associated with decreased RFS when compared to positive cases. HER2 present no relationship with GIST patients' prognosis. HER4 positive expression significantly associated with disease recurrence in GISTs. Further subgroup studies revealed HER4 was an independent prognostic indicator especially for gastric GISTs, and also for gastric high-risk GISTs. In our study, detection of EGFR expression helps to precisely subdivide high-risk GISTs for different prognosis and probably predict outcomes for imatinib treatment. HER4 is a novel independent prognostic biomarker for gastric GISTs specifically, which could be potential therapeutic target in GISTs originated from stomach.

Keywords: EGFR; Gastrointestinal stromal tumor; HER2; HER4; prognosis.

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Figures

Figure 1
Figure 1
Relative expression levels of HER family in GISTs by quantitative real-time PCR.
Figure 2
Figure 2
Representative immunohistochemical stains for HER family in GISTs.
Figure 3
Figure 3
Kaplan-Meier survival analyses with log-rank test for RFS of GISTs sorted by different tumor site (A) and modified NIH criteria (B).
Figure 4
Figure 4
EGFR negative expression predicts poor prognosis in high-risk GISTs (A) and imatinib treatment outcome (B).
Figure 5
Figure 5
Expression of HER4 for predicting prognosis in GISTs (A), stomach subgroup of GISTs (B), high-risk GISTs (C) and stomach subgroup of high-risk GISTs (D) with operation only.
See this image and copyright information in PMC

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