HER3 expression in patients with primary colorectal cancer and corresponding lymph node metastases related to clinical outcome

Lédel, Frida; Hallström, Marja; Ragnhammar, Peter; Ӧhrling, Katarina; Edler, David

doi:10.1016/j.ejca.2013.11.008

Cited by 45 publications

(52 citation statements)

References 25 publications

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“…ErbB1 is overexpressed in patients with CRC (24), and high expression levels of ErbB3 have been observed in 70% of primary CRC tumors (25). In the present study, the mRNA expression levels of ErbB3 were significantly increased in CRC tissues, compared with those in ANM tissues, whereas the mRNA expression levels of ErbB1 were significantly decreased in CRC tissues, compared with those in ANM tissues.…”

Section: B a B Amentioning

confidence: 40%

Downregulation of epidermal growth factor receptor family receptors and ligands in a mutant K-ras group of patients with colorectal cancer

Nagaoka

Kitaura

Miyata

et al. 2016

Molecular Medicine Reports

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Abstract. The present study investigated the expression profiles of the epidermal growth factor receptor (EGFR) family, which consists of four transmembrane tyrosine kinase receptors and their eight ligands, in 122 patients with colorectal cancer (CRC) using reverse transcription-quantitative polymerase chain reaction analysis. On comparison of the CRC primary tumor and matched adjacent normal mucosa (ANM) tissue samples, the mRNA expression levels of ErbB3, but not ErbB1, were significantly increased in CRC tissue samples, compared with those in the ANM tissues. The expression levels of the ligands exhibited opposing trends to their corresponding receptors, including EGF, BTC, AREG, EREG and HB-EGF, which were increased in the CRC tissues, whereas NRG1 and NGR2 were decreased in thee CRC tissues, compared with those in the AMN tissues. Subsequently, the present study investigated the frequency of K-ras mutations in the patients with CRC. The K-ras mutations were found to be present in 36.8% (45/122) of the cases, however, no correlation was observed between K-ras mutations and clinicopathological characteristics. In the CRC tissues, the expression levels of the EGFR family receptors and their ligands were determined in wild-type and mutant K-ras CRC cases. The expression levels of ErbB1, ErbB2, ErbB3, BTC, AREG, EREG, NRG1 and NRG2 were significantly decreased in the mutant K-ras cases, compared with those in the wild-type K-ras cases. These results suggested that the tumorigenesis of CRC with wild-type K-ras was mediated through, not only ErbB1, but also through the ErbB2 and ErbB3 pathways. Notably, although ErbB2 does not bind any ErbB ligands, ErbB2 may activate tumorigenesis via a heterodimer, rather than a homodimer. Therefore, the results of the present study suggest that the most effective strategy to target not only ErbB1, but also ErbB2 and ErbB3, is the use of monoclonal antibody treatment.

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Section: B a B Amentioning

confidence: 40%

Downregulation of epidermal growth factor receptor family receptors and ligands in a mutant K-ras group of patients with colorectal cancer

Nagaoka

Kitaura

Miyata

et al. 2016

Molecular Medicine Reports

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“…In our previous study, 63% of the colon tumors had high HER3 expression and, notably, the rectal tumors showed high HER3 expression in 87.5% of the tumors [9]. The association between tumor localization in the colon and HER3 expression is a novel finding in colon cancer (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

“…Previously, we reported a study of 236 CRC patients (172 colon and 64 rectum) where high HER3 expression was prognostic regarding OS in the entire group of patients and in the subgroup of stage II colon cancer [9]. These findings led to this unique, enlarged and refined study of colon cancer, stage II and III.…”

Section: Discussionmentioning

confidence: 99%

“…The 521 patients were a part of the Swedish cohort of colon cancer patients in the Nordic trials. The patient material in this study included 172 colon cancer cases from our pilot study and was then enlarged up to 521 patients [9]. The Dukes staging system and the stage I-IV system for colon cancer were used in the pathology reports.…”

Section: Patientsmentioning

confidence: 99%

“…HER3 inhibiting antibodies are under development and already in early clinical trials [8]. Regarding the significance of HER3 in colorectal cancer (CRC), the results are few and differ in prognosticity [7,9]. HER3 expression in exclusively colon cancer is even less studied.…”

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confidence: 99%

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HER3 expression is correlated to distally located and low-grade colon cancer

et al. 2016

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Background HER3 is a member of the human epidermal growth factor receptor complex (EGFR, HER2, HER3 and HER4). It has been investigated as a prognostic biomarker in colorectal cancer but is sparingly studied in colon cancer. HER3 can affect cellular proliferation, differentiation and migration in oncogenesis through ligand binding and activation of intracellular signal pathways. Recently, we found that expression of cell surface HER3 can be detected at a high extent in primary colorectal tumors, lymph node and liver metastases and that it correlated with poor prognosis. This large, explorative, retrospective study evaluates the prognostic value of HER3 in colon cancer and the association of HER3 to tumor location. Material and methods. Immunohistochemical detection with a monoclonal HER3 antibody in primary colon tumors of stage II and III, from 521 patients, was performed. Results HER3 was expressed at high levels in 67% of the colon tumors. High HER3 expression was associated with distal tumor location (p50.0001) and low-grade tumor (p50.0001). In the group of patients with distal colon cancer (230/521), HER3 expression correlated to shorter disease-free survival (DFS) (p ¼ 0.03) in the univariate analysis and in the multivariate analysis, a hazard ratio of 0.56 (95% CI 0.31-0.99) (p ¼ 0.047) was observed. Conclusion In this explorative, retrospective study, high HER3 expression in colon cancer was associated to distal colon location and low-grade tumor. High HER3 expression was of prognostic value according to DFS in distal colon cancer in univariate and multivariate analysis. We could not find a significant value of HER3 expression with respect to overall survival (OS).

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Genetically Engineered Antibody Functionalized Platinum Nanoparticles Modified CVD‐Graphene Nanohybrid Transistor for the Detection of Breast Cancer Biomarker, HER3

Rajesh

Gao

Vishnubhotla

et al. 2016

Adv Materials Inter

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Cancer is a leading cause of death worldwide and a major public health concern. Breast cancer is the most common cancer among American women, except for skin cancers and is the second leading cause of cancer-related death for women in the United States. [ 1 ] During the past decade researchers Biosensors based on graphene fi eld effect transistors (GFETs) decorated with antibody-functionalized platinum nanoparticles (PtNPs) are developed for the quantitative detection of breast cancer biomarker HER3. High-quality chemical vapor deposited graphene is prepared and transferred over gold electrodes microfabricated on an SiO 2 /Si wafer to yield an array of 52 GFET devices. The GFETs are modifi ed with PtNPs to obtain a hybrid nanostructure suitable for attachment of HER3-specifi c, genetically engineered thiol-containing single-chain variable fragment antibodies (scFv) to realize a biosensor for HER3. Physical and electrical characterization of Bio-GFET devices is carried out by electron microscopy, atomic force microscopy, Raman spectroscopy, and current-gate voltage measurements. A concentration-dependent response of the biosensor to HER3 antigen is found in the range 300 fg mL −1 to 300 ng mL −1 and is in quantitative agreement with a model based on the Hill-Langmuir equation of equilibrium thermodynamics. Based on the doseresponse data, the dissociation constant is estimated to be 800 pg mL −1 , indicating that the high affi nity of the scFv antibody is maintained after immobilization. The limit of detection is 300 fg mL −1 , showing the potential for PtNP/G-FETs to be used in label-free biological sensors.

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HER3 expression in patients with primary colorectal cancer and corresponding lymph node metastases related to clinical outcome

Cited by 45 publications

References 25 publications

Downregulation of epidermal growth factor receptor family receptors and ligands in a mutant K-ras group of patients with colorectal cancer

Downregulation of epidermal growth factor receptor family receptors and ligands in a mutant K-ras group of patients with colorectal cancer

HER3 expression is correlated to distally located and low-grade colon cancer

Genetically Engineered Antibody Functionalized Platinum Nanoparticles Modified CVD‐Graphene Nanohybrid Transistor for the Detection of Breast Cancer Biomarker, HER3

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