Lack of prognostic significance of epidermal growth factor receptor and the oncoprotein p185HER-2 in patients with systemically untreated non-small-cell lung cancer: an immunohistochemical study on cryosections

Pfeiffer, Per; Clausen, Per P.; Andersen, Kurt; Rose, Carsten

doi:10.1038/bjc.1996.320

Cited by 128 publications

(56 citation statements)

References 29 publications

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“…Careful review of the data presented by Kern et al (1990) reveals that their stage IIIA patients had a better prognosis than the patients in stage II and that the pN-category was not of significant prognostic importance (P = 0.95). Pfeiffer et al (1996) did not report differences in survival in AC overexpressing p185 however, the staining frequency in AC was only 26%. In our study, p185 overexpression is of significant prognostic importance for AC histology (P < 0.01) by univariate analysis but not of independent prognostic importance by multivariate analysis.…”

Section: Discussionmentioning

confidence: 80%

“…Overerexpression of p185 were reported in 28-80% AC (Kern et al, 1990;Bongiorno et al, 1994;Tateishi et al, 1991;Shi et al, 1992;Pfeiffer et al, 1996), 2-45% SCC (Kern et al, 1990;Pfeiffer et al, 1996;Shi et al, 1992;Tateishi, 1992;Volm et al, 1992) and 0-20% LC (Kern et al, 1990;Pfeiffer et al, 1996). Some of these studies used paraffin embedded slides (Kern et al, 1990;Tateishi, 1992;Volm et al, 1992) or applied p185 antiserum (Kern et al, 1990;Tateishi et al, 1991;Pfeiffer et al, 1996) for immunohistochemistry. Chiu et al (1994) could convincingly demonstrate in a controlled comparative analysis of paraffin-embedded slides and cryostat sections that rates of p185 overexpression were approximately doubled in cryostat sections.…”

Section: Discussionmentioning

confidence: 99%

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Multiple molecular marker testing (p53, C-Ki-ras, c-erbB-2) improves estimation of prognosis in potentially curative resected non-small cell lung cancer

et al. 2000

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Summary A prospective study was performed in patients with non-small cell lung cancer (NSCLC) to evaluate the prognostic importance of multiple molecular marker (p53, c-Ki-ras, c-erbB-2) testing. 103 patients with potentially curative resections (RO resection) for NSCLC in histopathological stages I-IIIA were included. SSCP analysis and DNA sequencing for p53 and c-Ki-ras genes were performed on paired tumour and normal lung tissue samples and immunohistochemistry (c-erbB-2) was done on frozen tissue sections with a specific anti-c-erbB-2 monoclonal antibody. 46/103 (44.6%) NSCLC showed p53 mutations and 17/103 (16.5%) c-Ki-ras mutations including 12/37 (32.4%) adenocarcinomas. Overexpression of c-erbB-2 (p185) was detected in 56/103 (54.4%) tumours. 24/103 (23.3%) NSCLC were negative for alterations in all 3 parameters (c-Ki-ras, p53 and p185) whereas 79/103 (76.7%) were positive for at least one of the 3 parameters. In a regression model including a multiple molecular marker parameter (negative for all 3 markers versus positive for at least one marker), histopathological stage (P < 0.00001), respectively the pT (P < 0.01) and pN (P < 0.00001) categories and the multiple molecular marker parameter (P < 0.01) were of significant prognostic importance. This study demonstrates that testing 3 molecular markers (c-Ki-ras, p53 and c-erbB-2) improves estimation of prognosis compared to single marker testing and appears to define low (82.6% ± 7.9% 5-year survival) and high risk (40.2% ± 5.5% 5-year survival) groups for treatment failure in potentially curative (RO) resected NSCLC.

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Multiple molecular marker testing (p53, C-Ki-ras, c-erbB-2) improves estimation of prognosis in potentially curative resected non-small cell lung cancer

et al. 2000

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“…Another unsolved problem is the association between HER2 status and prognosis in lung cancer patients. Overexpression of the HER2 protein is associated with shorter survival in some, 1,5,16 but not all, 4,6,17,18 reports. Overexpression of p185 HER2 was evaluated by IHC in those studies.…”

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confidence: 98%

“…[1][2][3][4][5][6] This oncogene family encodes for the growth factor tyrosine kinase receptors, which activate the intracellular signal-transduction pathway for cell proliferation. The product of the HER2 (erbB2) gene is a 185 dalton transmembrane protein (p185 HER2 ) tyrosine kinase.…”

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confidence: 99%

Correlation between encoded protein overexpression and copy number of the HER2 gene with survival in non‐small cell lung cancer

Nakamura

Saji

Ogata

et al. 2002

Intl Journal of Cancer

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The HER2 oncogene, which encodes the tyrosine kinase receptor, is commonly overexpressed in several types of cancer. Treatment using a humanized monoclonal antibody bound to HER2 product is becoming standard therapy for advanced breast cancer. Overexpression occurs in approximately 30% of non-small cell lung cancers (NSCLCs) and has been associated with poor prognosis. However, the frequency of a genetic aberration in the HER2 gene in lung cancer and the association between gene amplification and prognosis are poorly defined. To clarify these relationships, we simultaneously analyzed protein overexpression by immunohistochemistry (IHC) and determined the gene copy number by FISH in 50 surgical specimens of NSCLC. A lowgrade increase in the copy number (3 to 8 copies) of the HER2 gene was detected in 44% of tumors. Most represented polysomy of chromosome 17. Protein overexpression was observed in 26%. Overexpression was detected in adenocarcinoma more frequently than in squamous cell carcinoma. No significant correlation was observed between copy number increase and overexpression. Neither gene copy number increase nor overexpression correlated with survival. We conclude that the significance of HER2 status in NSCLC is different from that in breast cancer because high-grade amplification occurs rarely.

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“…Immunohistochemical studies have reported EGFR overexpression in 22 -81% of NSCLC tumours depending on the antibody used and cut point that defines overexpression (Veale et al, 1987;Volm et al, 1993;Pfeiffer et al, 1996;Cornianu and Tudose, 1997;Pastorino et al, 1997;Rusch et al, 1997;Fontanini et al, 1998;Greatens et al, 1998;D'Amico et al, 1999;Fu et al, 1999;Cox et al, 2000;Ohsaki et al, 2000;Selvaggi et al, 2002;Hirsch et al, 2003;Kanematsu et al, 2003;Mukohara et al, 2003;Onn et al, 2003). The majority of these studies have failed to demonstrate an association with prognosis (Table 1).…”

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confidence: 99%

Coexpression of epidermal growth factor receptor with related factors is associated with a poor prognosis in non-small-cell lung cancer

2004

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The epidermal growth factor receptor (EGFR) is commonly expressed in non-small-cell lung cancer (NSCLC) and promotes a host of mechanisms involved in tumorigenesis. However, EGFR expression does not reliably predict prognosis or response to EGFR-targeted therapies. The data from two previous studies of a series of 181 consecutive surgically resected stage I -IIIA NSCLC patients who had survived in excess of 60 days were explored. Of these patients, tissue was available for evaluation of EGFR in 179 patients, carbonic anhydrase (CA) IX in 177 patients and matrix metalloproteinase-9 (MMP-9) in 169 patients. We have previously reported an association between EGFR expression and MMP-9 expression. We have also reported that MMP-9 (P ¼ 0.001) and perinuclear (p)CA IX (P ¼ 0.03) but not EGFR expression were associated with a poor prognosis. Perinuclear CA IX expression was also associated with EGFR expression (Po0.001). Multivariate analysis demonstrated that coexpression of MMP-9 with EGFR conferred a worse prognosis than the expression of MMP-9 alone (Po0.001) and coexpression of EGFR and pCA IX conferred a worse prognosis than pCA IX alone (P ¼ 0.05). A model was then developed where the study population was divided into three groups: group 1 had expression of EGFR without coexpression of MMP-9 or pCA IX (number ¼ 21); group 2 had no expression of EGFR (number ¼ 75); and group 3 had coexpression of EGFR with pCA IX or MMP-9 or both (number ¼ 70). Group 3 had a worse prognosis than either groups 1 or 2 (P ¼ 0.0003 and 0.027, respectively) and group 1 had a better prognosis than group 2 (P ¼ 0.036). These data identify two cohorts of EGFR-positive patients with diametrically opposite prognoses. The group expressing either EGFR and or both MMP-9 and pCA IX may identify a group of patients with activated EGFR, which is of clinical relevance with the advent of EGFR-targeted therapies.

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Lack of prognostic significance of epidermal growth factor receptor and the oncoprotein p185HER-2 in patients with systemically untreated non-small-cell lung cancer: an immunohistochemical study on cryosections

Cited by 128 publications

References 29 publications

Multiple molecular marker testing (p53, C-Ki-ras, c-erbB-2) improves estimation of prognosis in potentially curative resected non-small cell lung cancer

Multiple molecular marker testing (p53, C-Ki-ras, c-erbB-2) improves estimation of prognosis in potentially curative resected non-small cell lung cancer

Correlation between encoded protein overexpression and copy number of the HER2 gene with survival in non‐small cell lung cancer

Coexpression of epidermal growth factor receptor with related factors is associated with a poor prognosis in non-small-cell lung cancer

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