Prognostic influence of the co-expression of epidermal growth factor receptor and c-erbB-2 protein in human lung adenocarcinoma

Tateishi, Masahiro; Ishida, Tatsuhiro; Kohdono, Satoshi; Hamatake, Motoharu; Fukuyama, Yasuro; Sugimachi, Keizō

doi:10.1016/0960-7404(94)90006-x

Cited by 70 publications

(44 citation statements)

References 17 publications

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“…c-erbB-2 overexpression regulates cell adhesion and invasive growth of cancer through its association with the cadherin -catenin complex (Ochiai et al, 1994) and is associated with increased migratory capacity (Bernstein et al, 1994). The coexpression of c-erbB-2 with the EGF-R seems to be more frequent in patients with metastases and seems to be associated with inferior survival (Tateishi et al, 1994). Moreover, c-erbB-2 overexpression defined a subgroup of node-negative patients with low angiogenesis and prognosis similar to patients bearing high angiogenesis (Giatromanolaki et al, 1996b), supporting the idea that c-erbB-2 expression is a mechanism activated in NSCLC to enable cancer cell migration in tumours with poor vasculature.…”

Section: Discussionmentioning

confidence: 99%

“…A total of 39 studies, published between 1990 and 2002, were found eligible (Kern et al, 1990(Kern et al, , 1994Tateishi et al, 1991Tateishi et al, , 1994Volm et al, 1992Volm et al, , 1993aHarpole et al, 1995aHarpole et al, , b, 1996Giatromanolaki et al, 1996a, b;Pfeiffer et al, 1996;Koukouraki et al, 1997Koukouraki et al, , 2000MacKinnon et al, 1997;Pastorino et al, 1997;Visscher et al, 1997;Yu et al, 1997;Graziano et al, 1998;Greatens et al, 1998;Hsieh et al, 1998;Kim et al, 1998;Kwiatkowski et al, 1998;Nemunaitis et al, 1998;Cantero et al, 1999Cantero et al, , 2000D'Amico et al, 1999;Fu et al, 1999;Moldvay et al, 2000;Schneider et al, 2000;Ardizzoni et al, 2001;Brabender et al, 2001;Liao et al, 2001;Shou et al, 2001;Carbognani et al, 2002;Han et al, 2002;Hirsch et al, 2002;Potti et al, 2002;Selvaggi et al, 2002). Nine of the articles were excluded because identical cohorts of patients were used (studies that were excluded and included were, respectively, references (Cantero et al, 1999) and (Cantero et al, 2000), (Giatromanolaki et al, 1996b;…”

Section: Studies Selection and Characteristicsmentioning

confidence: 99%

“…Nine of the articles were excluded because identical cohorts of patients were used (studies that were excluded and included were, respectively, references (Cantero et al, 1999) and (Cantero et al, 2000), (Giatromanolaki et al, 1996b;Koukourakis et al, 1997Koukourakis et al, , 2000 and (Giatromanolaki et al, 1996a), (Harpole et al, 1995a, b) and (Harpole et al, 1996), (Kern et al, 1994) and (Kern et al, 1990), (Tateishi et al, 1991) and (Tateishi et al, 1994), (Volm et al, 1992) and (Volm et al, 1993a, b).…”

Section: Studies Selection and Characteristicsmentioning

confidence: 99%

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The role of HER-2/neu expression on the survival of patients with lung cancer: a systematic review of the literature

et al. 2003

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C-erbB-2 prognostic value for survival in patients with lung cancer remains controversial. We performed a systematic review of the literature to clarify its impact. Studies were identified by an electronic search in order to aggregate the survival results, after a methodological assessment using the scale of the European Lung Cancer Working Party. To be eligible, a study had to deal with cerbB-2 assessment in lung cancer patients and to analyse survival according to c-erbB-2 expression. In total, 30 studies were eligible: 24 studies dealt with non-small-cell lung carcinoma (NSCLC), five with adenocarcinoma and one study dealt with small-cell carcinoma. In all, 31% of the patients were positive for c-erbB-2. According to c-erbB-2 expression, 13 studies were 'negative' (significant detrimental effect on survival), one 'positive' (significant survival improvement) and 16 not significant. Significant studies had a better subscore relative to analysis and results report than nonsignificant studies. In total, 86% of the significant studies and only 56% of the nonsignificant studies were evaluable for the meta-analysis. This suggests a possible bias in our aggregated results. For NSCLC, the hazard ratio was 1.55 (95% CI: 1.29 -1.86) in favour of tumours that do not express c-erbB-2. In conclusion, the overexpression of c-erbB-2 might be a factor of poor prognosis for survival in NSCLC, but there is a potential bias in favour of the significant studies with an overestimation risk of the magnitude of the true effect of c-erbB-2 overexpression.

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Section: Discussionmentioning

confidence: 99%

Section: Studies Selection and Characteristicsmentioning

confidence: 99%

Section: Studies Selection and Characteristicsmentioning

confidence: 99%

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The role of HER-2/neu expression on the survival of patients with lung cancer: a systematic review of the literature

et al. 2003

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“…19 Although EGFR is more abundantly expressed in lung carcinoma, 20,21 erbB2 overexpression is less common; it is found in <35% of patients with nonsmall cell lung cancers, mainly in those with adenocarcinoma. 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.…”

Section: Discussionmentioning

confidence: 99%

“…21 However, results from phase II trials of trastuzumab as a treatment for NSCLC have not shown any advantage for most patients 22 and have provided insufficient evidence to proceed to phase III trials. 23 Because the presence of a mutation appears to be a determination of response to therapy, as is the case with gefitinib and EGFR mutations, we therefore investigated the erbB2 and EGFR gene mutation status. However, we have found only 1 erbB2 mutation from 122 Japanese lung cancer patients.…”

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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Skip metastasis in nonsmall cell lung carcinoma

Prenzel

Baldus

Mönig

et al. 2004

Cancer

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BACKGROUND Skip metastasis to mediastinal lymph nodes is a prognostic factor for patients with nonsmall cell lung carcinoma (NSCLC). Little is known about the biologic behavior of tumors with noncontinuous spread to the mediastinal lymph nodes. In patients with pN2 skip metastases, micrometastases to N1 lymph nodes, which only mimic skip metastases, have not been investigated. METHODS In a retrospective study, the authors analyzed the primary tumor specimens from 45 patients with pN2 NSCLC (18 patients had squamous cell carcinomas, 23 had adenocarcinomas, and 4 had large cell carcinomas). They immunohistochemically evaluated the expression of p21, p53, MUC‐1, Bcl‐2, c‐ErbB‐2, and E‐cadherin. Survival rates and biomarker expression levels were compared between patients with pN2 disease and infiltration of N1 lymph nodes (without skip metastasis [n = 28]) and patients with pN2 disease without N1 infiltration (with skip metastasis [n = 17]). To evaluate micrometastasis in the pN1 lymph nodes of 17 patients with skip metastases, lymph nodes were stained using the anticytokeratin antibody, AE1/AE3. RESULTS The 5‐year survival rate of patients with skip metastases was 41%, compared with 14% for patients without skip metastases (P = 0.019). In a multivariate analysis, the incidence of skip metastases did not vary significantly according to gender, age, histology, pT status, or cM status. Three skip‐positive patients (17.6%) had micrometastatic tumor involvement of pN1 lymph nodes. After adding these patients to the group of patients without skip metastases, there was still a significant difference in survival between the two groups. p53, MUC‐1, c‐ErbB‐2, and E‐cadherin expression levels in primary tumor specimens were not significantly different in patients with continuous metastasis and patients with skip metastases. Patients with skip metastases expressed lower levels of p21 (P = 0.026), whereas Bcl‐2 expression levels were considerably higher (P = 0.019) compared with the corresponding levels in patients without skip metastases. CONCLUSIONS Patients with NSCLC and pN2 skip metastases have a more favorable prognosis than do patients with pN2 disease without skip metastases. Tumor specimens from these patients exhibit elevated expression of the antiapoptosis gene BCL2 and lower expression levels of p21 relative to patients with pN2 disease without skip metastases. Micrometastases occurred in 3 of 17 (17.6%) patients with pN2 disease and skip metastases diagnosed by routine histopathology. Cancer 2004. © 2004 American Cancer Society.

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Prognostic influence of the co-expression of epidermal growth factor receptor and c-erbB-2 protein in human lung adenocarcinoma

Cited by 70 publications

References 17 publications

The role of HER-2/neu expression on the survival of patients with lung cancer: a systematic review of the literature

The role of HER-2/neu expression on the survival of patients with lung cancer: a systematic review of the literature

EGFR and erbB2 mutation status in Japanese lung cancer patients

Skip metastasis in nonsmall cell lung carcinoma

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