Immunohistochemical analysis of epidermal growth factor receptor family members in stage I non-small cell lung cancer

Lai, Wu‐Wei; Chen, Fen Fen; Wu, Ming; Chow, Nan Haw; Su, Wu Chou; Chia, Mi; Su, Pei Fang; Chen, Helen; Mu, Liangshan; Tseng, Yau‐Lin

doi:10.1016/s0003-4975(01)03207-6

Cited by 27 publications

(19 citation statements)

References 12 publications

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“…21 Amplification of EGFR and erbB2 mRNA 22 or overexpression of their proteins 23 has been found to relate to survival in patients with NSCLC, although contradictory results have also been reported. 24,25 The drug trastuzumab, a humanized antibody against the extracellular domain of erbB2, has been approved for treatment of metastatic breast cancer and is most effective in breast cancer with erbB2 amplification. Preliminary results suggested that the combination of chemotherapy and trastuzumab is well tolerated for NSCLC.…”

Section: Discussionmentioning

confidence: 99%

EGFR and erbB2 mutation status in Japanese lung cancer patients

Sasaki

Shimizu

Endo

et al. 2005

Intl Journal of Cancer

152

111

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Much evidence has accumulated that the epidermal growth factor receptor (EGFR) and its family members are strongly implicated in the development and progression of lung cancers. Somatic mutations of the EGFR gene were found in about 25-40% of Japanese lung cancer patients. More recently, erbB2 mutations are found in about 4% of European-derived lung cancer patients. We have investigated EGFR and erbB2 mutation status in 95 surgically treated nonsmall cell lung cancer (NSCLC) cases from Nagoya City University Hospital. Seventy-five adenocarcinoma cases were included. The presence or absence of EGFR and ernB2 mutations of kinase domains were analyzed by reverse transcription polymerase chain reaction (RT-PCR) amplifications and direct sequences. We have also investigated erbB2 mutation status in 27 surgically treated NSCLC cases followed by treatment with gefitinib from Kinki-chuo Chest Medical Center. EGFR mutations (CTGfiCGG; L858R) were found from 14 of 95 lung cancer patients. We also detected the deletion 1a-type mutations from 9 patients and deletion 4-type mutations from 6 patients in exon 19. In exon 20, 4 mutations including 2 novel mutations were found. Total EGFR mutations were present in 35 patients (36.8%). These mutation statuses were significantly correlated with gender (women 73.3% vs. men 20%, p < 0.0001), smoking status (never smoker 69.4% vs. smoker 16.9%, p < 0.0001), pathologic subtypes (adenocarcinoma 45.1% vs. nonadenocarcinoma 12.5%, p 5 0.0089) and differentiation status of the lung cancers (well 51% vs. moderately or poorly 18.4%, p 5 0.0021). On the other hand, erbB2 mutation was only found from 1 of 95 patients, at exon 20. This patient was female and a never smoker with adenocarcinoma. This 12 nucleotide insertion mutation (2324-2325 ins ATACGTGATGGC) was located in the exon 20 at kinase domain (775-776 ins YVMA). There was no erbB2 mutation in 27 gefitinib-treated NSCLC patients. In total, we have found only 1 erbB2 mutation from 122 (0.8%) Japanese NSCLC patients. There was a significantly higher erbB2 positive (21/31) ratio in EGFR mutant patients (13/25, 52.0%) compared to EGFR wild-type patients (10/ 62, 16.1%; p 5 0.0247). The NSCLC specimen with erbB2 mutation showed 11 immunoreactivity. The EGFR mutation status might correlate with the clinicopathologic features related to good response to gefitinib, such as gender, smoking history and pathologic subtypes of lung cancers. However, erbB2 mutation is rare from Japanese lung cancer and is of limited value for molecular target therapy. ' 2005 Wiley-Liss, Inc.Key words: EGFR; lung cancer; mutations; erbB2; Japanese Lung cancer is a major cause of death from malignant diseases, due to its high incidence, malignant behavior and lack of major advancements in treatment strategy.1 Lung cancer was the leading indication for respiratory surgery (42.2%) in 1998 in Japan.2 More than 15,000 patients underwent surgical operations at Japanese institutions in 1998. 2 The clinical behavior of the lung cancer is largely associated with its stage. ...

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Section: Discussionmentioning

confidence: 99%

EGFR and erbB2 mutation status in Japanese lung cancer patients

Sasaki

Shimizu

Endo

et al. 2005

Intl Journal of Cancer

152

111

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“…For example, it has been shown that ERBB-2 is not a major contributor to the development of drug resistance, but when ERBB-2 dimerizes with ERBB-3, this complex is associated with the development of significant drug resistance (Munster et al, 2002). ERBB-3 has also been shown to be a marker of poor prognosis in a study involving 73 lung cancer patients (Lai et al, 2001). This group immunohistochemically evaluated the expression of members of the epidermal growth factor receptor family, and ERBB-3 correlated with enhanced distant metastasis in this patient population.…”

Section: Discussionmentioning

confidence: 99%

A novel time-course cDNA microarray analysis method identifies genes associated with the development of cisplatin resistance

et al. 2004

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“…375 Coexpression of ERBB3 with other ERBB family members was indicative of tumor recurrence. 376 The expression of the proliferation-associated marker Ki-67 at a higher frequency in ERBB3-positive NSCLC cases than in ERBB3-negative tumors was suggestive of a contribution of ERBB3 to aggressive behavior; combination of elevated ERBB3, p53 and microvessel density predicted poor survival. 377 In an interesting real-time PCR-based study of expression of 56 receptor tyrosine kinases in early stage NSCLC, ERBB3 was one of 10 associated with metastasis development and decreased survival, along with EGFR and ERBB2.…”

Section: Respiratory Tissuesmentioning

confidence: 94%

The ERBB3 receptor in cancer and cancer gene therapy

2008

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ERBB3, a member of the epidermal growth factor receptor (EGFR) family, is unique in that its tyrosine kinase domain is functionally defective. It is activated by neuregulins, by other ERBB and nonERBB receptors as well as by other kinases, and by novel mechanisms. Downstream it interacts prominently with the phosphoinositol 3-kinase/AKT survival/mitogenic pathway, but also with GRB, SHC, SRC, ABL, rasGAP, SYK and the transcription regulator EBP1. There are likely important but poorly understood roles for nuclear localization and for secreted isoforms. Studies of ERBB3 expression in primary cancers and of its mechanistic contributions in cultured cells have implicated it, with varying degrees of certainty, with causation or sustenance of cancers of the breast, ovary, prostate, certain brain cells, retina, melanocytes, colon, pancreas, stomach, oral cavity and lung. Recent results link high ERBB3 activity with escape from therapy targeting other ERBBs in lung and breast cancers. Thus a wide and centrally important role for ERBB3 in cancer is becoming increasingly apparent. Several approaches for targeting ERBB3 in cancers have been tested or proposed. Small inhibitory RNA (siRNA) to ERBB3 or AKT is showing promise as a therapeutic approach to treatment of lung adenocarcinoma.

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Immunohistochemical analysis of epidermal growth factor receptor family members in stage I non-small cell lung cancer

Cited by 27 publications

References 12 publications

EGFR and erbB2 mutation status in Japanese lung cancer patients

EGFR and erbB2 mutation status in Japanese lung cancer patients

A novel time-course cDNA microarray analysis method identifies genes associated with the development of cisplatin resistance

The ERBB3 receptor in cancer and cancer gene therapy

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