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Open Access Research article

Prognostic significance of HER3 and HER4 protein expression in colorectal adenocarcinomas

Panteleimon Kountourakis12*, Kitty Pavlakis3, Amanda Psyrri12, Dimitra Rontogianni4, Nikolaos Xiros1, Efstratios Patsouris3, Dimitrios Pectasides1 and Theofanis Economopoulos1

Author Affiliations

1 Second Department of Internal Medicine-Propaedeutic, Athens University Medical School, Attikon university Hospital, Athens, Greece

2 Yale Cancer Center, New Haven, CT, USA

3 Pathology Department, Athens University Medical School, Greece

4 Pathology Department, Evangelismos Hospital, Athens-Hellas, Greece

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BMC Cancer 2006, 6:46  doi:10.1186/1471-2407-6-46

Published: 28 February 2006



Colorectal cancer remains a major cause of cancer mortality in the Western world. A limited number of studies has been conducted in respect of Her-3 and Her-4 expression and their correlation with clinical parameters and prognosis in colorectal carcinomas . In this study we sought to determine the pattern and the prognostic significance of HER-3 and HER-4 in colorectal adenocarcinoma.


We studied HER-3 and HER-4 protein expression in106 paraffin embedded specimens of primary colorectal tumors using immunohistochemistry. The pattern and protein expression levels of HER-3 and HER-4 were correlated with several clinical and pathological parameters.


HER-3 staining displayed membranous and cytoplasmic expression pattern in 18 (17%) and 30 samples (28,3%), respectively. HER-4 membranous and cytoplasmic expression was found in 20 (18,9%) and 32 samples (30,2%), respectively. Specimens regarded as positive for HER-3 cytoplasmic expression were associated with moderate tumor grade (p = 0,032) and older median age (p = 0,010). Specimens regarded as positive for HER-4 membranous protein expression were associated with involved lymphnodes (p = 0,0003). Similar results were obtained when considering Her-3 and Her-4 protein expression irrespective of their cellular localization. There was no correlation between the expression of HER-3 and HER-4 and patients outcome.


HER-4 membranous protein expression was found to predict for lymph nodes positivity in this cohort of patients with colorectal cancer.HER-4 expression status may identify tumors with aggressive biological behavior and increased metastatic potential.