Protein expression of HER2, 3, 4 in gastric cancer: correlation with clinical features and survival

He, Xuming; Li, Ding; Lin, Yuan; Shu, Man; Wen, Jian Ming; Xue, Ling

doi:10.1136/jclinpath-2014-202657

Cited by 31 publications

(39 citation statements)

References 37 publications

(40 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Depending on the presence of these isoforms, HER4 may show different intracellular localizations and varying clinical significance in malignancies. Previous studies on HER4 expression in GC failed to demonstrate a significant association with patients survival [15,39], and little is known about the function of NRG1 in relation to the subcellular distribution of HER4 in GC. In a review of breast cancer studies, while HER4 cytoplasmic expression was favorably associated with patient survival, the significance of HER4 expression localized to the nucleus with regard to survival was uncertain [18].…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of overexpression of NRG1 and its receptors, HER3 and HER4, in gastric cancer patients

et al. 2017

View full text Add to dashboard Cite

Neuregulin 1 (NRG1), a ligand for human epidermal growth factor (HER) 3 and HER4, can activates cell signaling pathways to promote carcinogenesis and metastasis. To investigate the clinicopathologic significance of NRG1 and its receptors, immunohistochemistry was performed for NRG1, HER3, and HER4 in 502 consecutive gastric cancers (GCs). Furthermore, HER2, microsatellite instability (MSI), and Epstein-Barr virus (EBV) status were investigated. NRG1 gene copy number (GCN) was determined by dual-color fluorescence in situ hybridization (FISH) in 388 available GCs. NRG1 overexpression was observed in 141 (28.1%) GCs and significantly associated with aggressive features, including infiltrative tumor growth, lymphovascular, and neural invasion, high pathologic stage, and poor prognosis (all P < 0.05), but not associated with EBV, MSI, or HER2 status. HER3 cytoplasmic and membranous expression were observed in 157 (31.3%) and 13 (2.6%), respectively. HER4 cytoplasmic expression was observed in 277 (55.2%), including 115 (22.9%) cases with nuclear expression. In contrast to NRG1, cytoplasmic expression of HER3 and HER4 proteins were not associated with survival, but GC patients with HER3 membranous expression showed significantly worse survival. In addition, HER4 nuclear expression was inveresely correlated with patients outcome in GC. NRG1 overexpression was also closely correlated with HER3 (P = 0.034) and HER4 (P < 0.001) cytoplasmic expression. NRG1 GCN gain (GCN ≥ 2.5) was detected in 14.7% patients, including two cases of amplification, and was moderately correlated with NRG1 overexpression (κ, 0.459; P < 0.001). Multivariate analysis identified NRG1 overexpression as an independent prognostic factor for survival (P = 0.040), unlike HER3 and HER4 expression. In 14 HER2positive GC with trastzumab combined chemotherapy, coexpression of NRG1 and HER3 was detected in 2 (14.3%) cases, and these GC patients group with coexpression of NRG1 and HER3 also showed a shorter PFS (P = 0.005).Although our results indicate a lack of prognostic significance of HER3 and HER4 overexpression in GC, overexpression of their ligand, NRG1, was associated with aggressive clinical features and represented an independent unfavorable prognostic factor. Therefore, NRG1 is a potential prognostic and therapeutic biomarker in GC patients.--

show abstract

Section: Discussionmentioning

confidence: 99%

Clinical significance of overexpression of NRG1 and its receptors, HER3 and HER4, in gastric cancer patients

et al. 2017

View full text Add to dashboard Cite

show abstract

“…However, other studies demonstrated that the high expression of certain HER family receptors determined the histological type of cancer (e.g., stomach cancer) [34] and affected patient survival. Furthermore, HER-3 overexpression in stomach cancer aggravated the patients’ condition and reduced their survival [34, 35]. High HER-2 expression in prostate adenocarcinoma was correlated with the serum level of prostate-specific antigen and had an important role in disease progression [36].…”

Section: Role Of Changes In Receptor Expression Density In Health Andmentioning

confidence: 99%

Expression Density of Receptors as a Potent Regulator of Cell Function and Property in Health and Pathology

Sennikov

Alshevskaya

Zhukova

et al. 2018

Int Arch Allergy Immunol

View full text Add to dashboard Cite

The expression of cytokine receptors has a crucial role in many cellular processes. Recent studies reported that changes of receptor expression could control the action of mediators on target cells. The initiation of different signaling pathways and, therefore, specific effects on cells, depends on certain components forming the cytokine-receptor complex. These mechanisms control the immune response and affect both the course of diseases (oncological, autoimmune, inflammatory) and the effectiveness of therapy. This review describes the potential of immune mediator receptors to regulate the efficiency of cytokine activity during pathologic processes and ensure the variability of their biological effects. Our aim was to investigate the spectrum of potential roles of changes in mediator receptor expression for main classes of pathologies. For all major types of immune mediators (cytokines, interleukins, chemokines, growth factors, and tumor necrosis factors), it has been shown that changes in their receptor expression are associated with impaired functioning of the organism in chronic diseases.

show abstract

“…HER3 está sobreexpresado en el 87% de los tumores gástricos 15 , y es más común en el citoplasma (64%) que en el núcleo (34%) o la membrana (2%) 6,7 , aunque Choi, et al 15 observaron que HER3 se encuentra principalmente en el núcleo. Para algunos autores, la sobreexpresión de HER3 se relaciona con el subtipo intestinal de CG 6,7,16 , mientras que para otros se relaciona con el subtipo difuso 17 . Por otra parte, también se ha descrito la falta de asociación con algún subtipo de CG 18,19 .…”

Section: Sobreexpresiónunclassified

“…Además, la sobreexpresión se asocia con tumores bien y moderadamente diferenciados, edad avanzada, mayor invasión tumoral, afectación ganglionar, metástasis tumoral y pobre tasa de sobrevida l6, 7,18 . La expresión nuclear de HER3 en el CG se asocia con invasión vascular y linfática, y con baja supervivencia (HER3+ 24-28 meses vs. HER3− 45-47 meses) 6,16 . La expresión de HER4 parece ser mayor en los tejidos gástricos tumorales que en la mucosa gástrica adyacente 6 .…”

Section: Sobreexpresiónunclassified

“…Esto es concordante con el papel de HER4 en la diferenciación y la respuesta antiproliferativa 20 . A pesar de su supuesta implicación en un mejor pronóstico en los pacientes con CG, algunos informes han demostrado que la sobreexpresión de HER4 está asociada con etapas avanzadas de la enfermedad 16 y con la presencia de células en anillo de sello 21 .…”

Section: Sobreexpresiónunclassified

See 1 more Smart Citation

Los receptores epidérmicos humanos en el cáncer gástrico: alteraciones moleculares y su papel como diana terapéutica

Bustos-Carpinteyro

Magaña-Torres

González-García

et al. 2017

GMM

View full text Add to dashboard Cite

Protein expression of HER2, 3, 4 in gastric cancer: correlation with clinical features and survival

Abstract: HER3 is correlated with the malignant biological behaviour of GC. Expression of HER3 is a significant predictor of poor survival in GC. Therefore, the development of HER3-targeted agents may provide new possibilities in the treatment of GC.

Cited by 31 publications

References 37 publications

Clinical significance of overexpression of NRG1 and its receptors, HER3 and HER4, in gastric cancer patients

Clinical significance of overexpression of NRG1 and its receptors, HER3 and HER4, in gastric cancer patients

Expression Density of Receptors as a Potent Regulator of Cell Function and Property in Health and Pathology

Los receptores epidérmicos humanos en el cáncer gástrico: alteraciones moleculares y su papel como diana terapéutica

Contact Info

Product

Resources

About