Epidermal growth factor receptor expression in human pancreatic cancer: Significance for liver metastasis

Tobita, Kosuke; Kijima, Hiroshi; Dowaki, Shoichi; Kashiwagi, Hirokazu; Ohtani, Yasuo; Oida, Yasuhisa; Yamazaki, Hitoshi; Nakamura, Masato; Ueyama, Yoshito; Tanaka, Makiko; Inokuchi, Sadaki; Makuuchi, Hiroyasu

doi:10.3892/ijmm.11.3.305

Cited by 129 publications

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“…Most in vitro studies have shown that cancer cells modulated by EGFR activation have increased propensity for mitosis, proapoptosis, chemoresistance and angiogenesis. 4,5,[13][14][15][16]23 In addition, some reports have indicated that membranous EGFR activation is responsible for the regulation of intercellular adhesion such as cell-cell and cellmatrix adhesion. IGF1R activation has also been …”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that EGFR or HER-2 is overexpressed in 10-30% of pancreatic cancers. 13 EGFR overexpression was associated with a high risk of death, whereas HER-2 overexpression was correlated with glandular differentiation and early oncogenesis. [17][18][19] Previously, we reported that the clinical implication of cytoplasmic EGFR overexpression was distinct from that of membrane EGFR overexpression in pancreatic cancer, the former being correlated with a higher tumor grade and poorer patient prognosis than the latter.…”

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confidence: 98%

“…Many studies have shown that overexpression of EGFR and HER-2 is correlated with advanced disease stage, low patient survival rate, development of tumor metastasis and acquisition of chemoresistance. [13][14][15] As is the case for the IGF1R signaling pathway, the EGFR signaling pathway is also involved in cellular transformation, tumorigenesis and tumor vascularization. However, differences between the biological behaviors mediated by these two signaling pathways still remain unclear.…”

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confidence: 99%

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Potential crosstalk between insulin-like growth factor receptor type 1 and epidermal growth factor receptor in progression and metastasis of pancreatic cancer

et al. 2006

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The insulin-like growth factor receptor type 1 (IGF1R) and epidermal growth factor receptor (EGFR) are reportedly overexpressed in pancreatic cancer. However, the correlation between activated EGFR and IGF1R and their clinicopathological implications still remain unclear. The cellular localization and overexpression of IGF1R and EGFR were investigated immunohistochemically in primary invasive ductal pancreatic carcinomas obtained from 74 patients who underwent radical surgical resection. We also compared the status of IGF1R and EGFR overexpression between primary tumors and hepatic metastatic tumors obtained from 44 autopsied patients. Among the 74 surgically resected primary tumors, cytoplasm-and membrane-dominant EGFR overexpression was detected in 22 (30%) and 7 (9%), respectively, whereas cytoplasm-and membranedominant IGF1R overexpression was detected in 8 (11%) and 28 (38%), respectively. Membrane-dominant EGFR and cytoplasm-dominant IGF1R were more frequent in lower-grade tumors and correlated with favorable prognosis, whereas cytoplasm-dominant EGFR and membrane-dominant IGF1R were more frequent in highergrade tumors and correlated with poor prognosis. In 36 autopsy specimens of pancreatic tumor with concurrent overexpression of IGF1R and EGFR, there was an inverse correlation between the IGF1R and EGFR localization patterns (P ¼ 0.001). In the hepatic metastatic tumors obtained by autopsy, the incidences of both IGF1R and EGFR overexpression were much higher than in the surgically resected primary tumors. More than half of the autopsy cases consistently showed membrane-dominant EGFR expression in both the primary tumor and hepatic metastases, whereas IGF1R expression showed considerable variation. Crosstalk between differently localized IGF1R and EGFR might play a role in determining the biological aggressiveness of pancreatic cancer, although their cellular localization may often alter during the process of metastasis.

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Section: Discussionmentioning

confidence: 99%

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Potential crosstalk between insulin-like growth factor receptor type 1 and epidermal growth factor receptor in progression and metastasis of pancreatic cancer

et al. 2006

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“…Reports of expression of the ErbB receptor family, including the epidermal growth factor receptor (EGFR; ErbB1/HER1) and HER2; ErbB2/neu vary widely in PDAC. Studies have shown that immunohistochemical (IHC) expression of EGFR ranges from 41-70 % [11][12][13] in PDAC.…”

Section: Introductionmentioning

confidence: 99%

EGFR and HER2 inhibition in pancreatic cancer

et al. 2012

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Summary The aim of this study was to investigate the effect of lapatinib, a selective inhibitor of EGFR/HER2 tyrosine kinases, on pancreatic cancer cell lines both alone and in combination with chemotherapy. Two cell lines, BxPc-3 and HPAC, displayed the greatest sensitivity to lapatinib (IC 50 < 2 μM). Lapatinib also demonstrated some activity in three KRas mutated pancreatic cancer cell lines which displayed resistance to erlotinib. Drug effect/combination index (CI) isobologram analysis was used to study the interactions of lapatinib with gemcitabine, cisplatin and 5'deoxy-5'fluorouridine. Concentration-dependent anti-proliferative effects of lapatinib in combination with chemotherapy were observed. To evaluate the potential effect of lapatinib in pancreatic cancer tumours, and to identify a subset of patient most likely to benefit from lapatinib, expression of EGFR and HER2 were investigated in 72 pancreatic cancer tumour specimens by immunohistochemistry. HER2 membrane expression was observed in only 1 % of cases, whereas 44 % of pancreatic tumours expressed EGFR. Based on our in vitro results, lapatinib may provide clinical benefit in EGFR positive pancreatic ductal adenocarcinoma.

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“…Altered expression or constitutive activation of the epidermal growth factor receptor (EGFR/HER1/erbB1) commonly occurs in both primary and metastatic pancreatic cancers and is often a critical component in progressive growth and resistance to normal mechanisms of cell death (Lemoine et al, 1992;Schmiegel et al, 1997;Xiong and Abbruzzese, 2002). Epidermal growth factor receptor expression in pancreatic cancer has been correlated with tumour aggressiveness (Tobita et al, 2003).…”

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Phase I study of the humanised anti-EGFR monoclonal antibody matuzumab (EMD 72000) combined with gemcitabine in advanced pancreatic cancer

et al. 2006

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The humanised anti-epidermal growth factor receptor (EGFR) monoclonal antibody matuzumab (formerly EMD 72000) is active against pancreatic cancer in preclinical studies. This phase I study assessed the safety and potential benefit of combined treatment with matuzumab and standard-dose gemcitabine. Three groups of chemotherapy-naive advanced pancreatic adenocarcinoma patients (n ¼ 17) received escalating doses of matuzumab (400 mg weekly, 800 mg biweekly, or 800 mg weekly) and gemcitabine (1000 mg m -2 weekly in weeks 1 -3 of each 4-week cycle). Toxicity, antitumour activity, pharmacokinetic (PK) parameters, and pharmacodynamic (PD) markers in skin biopsies were evaluated. Severe treatment-related toxicities were limited to grade 3 neutropenia (n ¼ 3), leucopenia (n ¼ 1), and decreased white blood cell count (n ¼ 1). Common study drug-related adverse events were skin toxicities (grade 2 ¼ 6, grade 1 ¼ 7) and fever (grade 1 ¼ 4). Matuzumab inhibited phosphorylated EGFR and affected receptor-dependent signalling and transduction; effects were seen even in the lowest-dose group. Pharmacokinetic data were consistent with results of matuzumab monotherapy. Partial response (PR) or stable disease occurred in eight of 12 evaluated patients (66.7%), with three PRs among six evaluated patients in the group receiving 800 mg weekly. Matuzumab in biologically effective doses with standard gemcitabine therapy appears well tolerated. The combination is feasible and may have enhanced activity.

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Epidermal growth factor receptor expression in human pancreatic cancer: Significance for liver metastasis

Cited by 129 publications

References 0 publications

Potential crosstalk between insulin-like growth factor receptor type 1 and epidermal growth factor receptor in progression and metastasis of pancreatic cancer

Potential crosstalk between insulin-like growth factor receptor type 1 and epidermal growth factor receptor in progression and metastasis of pancreatic cancer

EGFR and HER2 inhibition in pancreatic cancer

Phase I study of the humanised anti-EGFR monoclonal antibody matuzumab (EMD 72000) combined with gemcitabine in advanced pancreatic cancer

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