ErbB family immunohistochemical expression in colorectal cancer patients with higher risk of recurrence after radical surgery

Baiocchi, Glauco; Lopes, Ademar; Coudry, Renata A.; Rossi, Mauro; Soares, Fernando Augusto; Aguiar, Samuel; Guimarães, Gustavo Cardoso; Ferreira, Fábio Oliveira; Nakagawa, Wilson Toshihiko

doi:10.1007/s00384-009-0702-6

Cited by 41 publications

(49 citation statements)

References 43 publications

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“…The sensitivity of other EGFR overexpressing human tumour cell lines to growth inhibition by the EGFR inhibitors has also been reported in other studies (20,29,43). However, to our knowledge there are only two studies which examine the expression pattern and prognostic significance of all EGFR family members in CRC patients (44,45). In one study, Lee et (45).…”

Section: Discussionmentioning

confidence: 54%

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Growth response of human colorectal tumour cell lines to treatment with afatinib (BIBW2992), an irreversible erbB family blocker, and its association with expression of HER family members

Modjtahedi¹

2011

Int J Oncol

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Abstract. Despite the approval of the anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs), cetuximab and panitumumab, for the treatment of colorectal cancer patients, there is currently no reliable predictive marker for response to therapy. In addition, the duration of response is often limited. Therefore, this study aimed to investigate the effect of afatinib, an irreversible erbB family blocker, as a single agent or in combination with cytotoxic drugs (5-fluorouracil, irinotecan and oxaliplatin) or mAb ICR62 on the proliferation of a panel of human colorectal tumour cell lines and the association between the expression levels of the EGFR family members and response to treatment. Of the cells examined, EGFR-overexpressing DiFi cells were the most sensitive to treatment with both afatinib (IC 50 =45 nM) and ICR62 (IC 50 =4.33 nM). Afatinib also inhibited the growth of other tumour cell lines with IC 50 values which ranged from 0.33 µM (CCL-221) to 1.62 µM (HCT-116). A significant association was found between the co-expression of EGFR, human epidermal growth factor receptor (HER)-2 and HER-3 and response to treatment with afatinib (R=0.915, P=0.021). Treatment with afatinib and cytotoxic drugs was accompanied by an increase in the proportion of these cells in the sub-G0/G1 and in the S and G2/M phase of the cell cycle, respectively. We conclude that afatinib as monotherapy or in combination with other drugs shows activity in colorectal tumour cells and that determination of the co-expression of HER family members should be conducted in clinical trials using drugs targeting erbB signaling. This approach could lead to the identification of a specific subpopulation of cancer patients more likely to benefit from erbB-directed therapy.

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Section: Discussionmentioning

confidence: 54%

“…However, to our knowledge there are only two studies which examine the expression pattern and prognostic significance of all EGFR family members in CRC patients (44,45). In one study, Lee et (45). These results suggest that the co-expression of EGFR family members is common in patients with CRC.…”

Section: Discussionmentioning

confidence: 99%

Growth response of human colorectal tumour cell lines to treatment with afatinib (BIBW2992), an irreversible erbB family blocker, and its association with expression of HER family members

Modjtahedi¹

2011

Int J Oncol

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“…expression tightly correlated with poor survival of patients with colorectal cancer (38,39). Nevertheless, further investigations concerning the HER3 status versus the genetic classification of the CRC tumors, namely, LOH, microsatellite instability, hereditary nonpolyposis colorectal cancer would be of interest to get further insights into the relevance of HER3 expression in different colon cancer subtypes.…”

Section: Discussionmentioning

confidence: 99%

Toward the Prognostic Significance and Therapeutic Potential of HER3 Receptor Tyrosine Kinase in Human Colon Cancer

Beji

Horst

Engel

et al. 2012

Clinical Cancer Research

105

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Purpose: Abnormal accumulation and dysregulation of the epidermal growth factor receptor family member HER3 is associated with the development of various human cancers including those of the breast, lung, and ovary. We have previously shown that in melanoma HER3 is frequently overexpressed and is associated with poor prognosis. However, the importance of HER3 in colon cancer and its putative prognostic significance is still unknown.Experimental Design: HER3 expression was analyzed in primary colon tumors from 110 patients by immunohistochemistry and correlated with time of progression. Parallel to this, the influence of HER3 overexpression on cell proliferation, migration, invasion, and apoptosis was investigated in four different colon cancer cell lines including DLD-1, LoVo, CaCO2, and T-84.Results: HER3 was detected at high frequency and exclusively at the membrane of the primary tumors. Elevated HER3 expression levels may serve as a putative prognostic marker because it associates with cell proliferation and decreased time to disease progression. High HER3 protein expression as well as phosphorylation levels were detected in tested cells. HER3 downregulation by RNA interference abrogated cell proliferation, migration, and invasion. In addition, suppression of HER3 resulted in a G 2 -M cell-cycle arrest, induced apoptosis, and led to morphologic changes in colon cancer cell lines. Furthermore, application of a monoclonal antibody specific to the extracellular portion of the receptor reduced heregulin-b1-induced migration and invasion and also induced apoptosis in colon cancer cell lines.Conclusion: We postulate that HER3 is critically involved in colon cancer progression and may serve as a novel target for therapeutic intervention. Clin Cancer Res; 18(4); 956-68. Ó2011 AACR.

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“…Two studies reported the relationship between HER3 overexpression and patient's outcome, but there is some controversy. One study showed HER3 overexpression was associated with a poor outcome of CRC patients (31), whereas two other studies including a recent meta-analysis in 12 studies showed that HER3 overexpression could not be linked with poor prognosis in CRC, despite association with short survival in patients with several types of solid tumors, including breast, ovarian cancers and melanoma (32,33). The reason for this discrepancy between studies may be primarily due to the difference in the antibody used in these studies.…”

Section: Discussionmentioning

confidence: 99%

Deficient HER3 expression in poorly-differentiated colorectal cancer cells enhances gefitinib sensitivity

Nakata

Tanaka

Ito

et al. 2014

International Journal of Oncology

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Abstract. Poorly-differentiated colorectal cancers (PD-CRC)show high metastatic potential and poor prognosis. However, molecular characteristics of PD-CRC remain unknown to date, particularly in molecular targeting therapy for patients with PD-CRC. In this study, we examined the expression of EGFR, HER2 and HER3 in PD-CRC by immunohistochemical analysis of archived clinical specimens of primary tumors and investigated the sensitivity of PD-CRC cell lines to gefitinib, a tyrosine kinase inhibitor for EGFR in vitro. We found that HER3 expression of PD-CRC among members of the HER family was significantly lower than that of well to moderately differentiated CRC (WMD-CRC) and 37% of the PD cases showed a EGFR + /HER2

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ErbB family immunohistochemical expression in colorectal cancer patients with higher risk of recurrence after radical surgery

Abstract: The immunohistochemical expression of ErbB3 and ErbB4 may identify a subgroup with stage II and III colorectal cancer at higher risk of recurrence.

Cited by 41 publications

References 43 publications

Growth response of human colorectal tumour cell lines to treatment with afatinib (BIBW2992), an irreversible erbB family blocker, and its association with expression of HER family members

Growth response of human colorectal tumour cell lines to treatment with afatinib (BIBW2992), an irreversible erbB family blocker, and its association with expression of HER family members

Toward the Prognostic Significance and Therapeutic Potential of HER3 Receptor Tyrosine Kinase in Human Colon Cancer

Deficient HER3 expression in poorly-differentiated colorectal cancer cells enhances gefitinib sensitivity

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