Epidermal growth factor receptor (EGFr) expression in non-small cell lung carcinomas correlates with metastatic involvement of hilar and mediastinal lymph nodes in the squamous subtype

Fontanini, Gabriella; Vignati, S; Bigini, D; Mussi, Alfredo; Lucchi, H.; Angeletti, Carlo Alberto; Pingitore, Raffaele; Pepe, Stefano; Basolo, Fulvio; Bevilacqua, Generoso

doi:10.1016/0959-8049(93)00421-m

Cited by 115 publications

(67 citation statements)

References 28 publications

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“…Stromal proliferation is an important, though poorly understood, collagenous host response to tumor invasion (28). Growth factors (29), extracellular matrix enzymes (30,31), and proliferative activity of tumor cells (4) form an intricate network of cooperative factors that regulate stromal proliferation. One of the first studies of the impact of stromal proliferation on the prognosis of lung adenocarcinoma was reported by Shimosato et al in 1980 (25).…”

Section: Discussionmentioning

confidence: 99%

Prognostic Values of Stromal Proportion and PCNA, Ki-67, and p53 Proteins in Patients with Resected Adenocarcinoma of the Lung

et al. 2000

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Section: Discussionmentioning

confidence: 99%

Prognostic Values of Stromal Proportion and PCNA, Ki-67, and p53 Proteins in Patients with Resected Adenocarcinoma of the Lung

et al. 2000

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“…7,8 Clinically, reduced E-cad expression was found to correlate with dedifferentiation, invasiveness, and poor prognosis in NSCLC, although there was an inconsistency regarding its dependability as a prognostic factor. [9][10][11] On the other hand, overexpression of EGFR was reported to be associated with lymph node involvement and poor prognosis in NSCLC. 11,12 Few investigations addressed the coexpression of E-cad and EGFR, 13 and the relation between this expression and patient survival in NSCLC.…”

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confidence: 99%

“…[9][10][11] On the other hand, overexpression of EGFR was reported to be associated with lymph node involvement and poor prognosis in NSCLC. 11,12 Few investigations addressed the coexpression of E-cad and EGFR, 13 and the relation between this expression and patient survival in NSCLC. The aim of this study was to utilize a high-throughput tissue microarray (TMA) and immunohistochemistry (IHC) for assessment of E-cad and EGFR expressions in two major subtypes of NSCLC, adenocarcinoma (AdC) and squamous cell carcinoma (SCC), to evaluate their association with clinicopathologic variables and patient survival, and to address their possible value as prognosticators.…”

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confidence: 99%

Altered E-cadherin and epidermal growth factor receptor expressions are associated with patient survival in lung cancer: a study utilizing high-density tissue microarray and immunohistochemistry

et al. 2004

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E-cadherin (E-cad) and epidermal growth factor receptor (EGFR) are important cell adhesion and signaling pathway mediators. This study aimed to assess their expression in lung adenocarcinoma (AdC) and squamous cell carcinoma (SCC) and their association with clinicopathologic variables. In all, 130 resectable lung cancers (stages I-IIIA) were studied using a high-density tissue microarray. Two to three cores from each case were arrayed into three blocks using a Beecher system. Immunohistochemistry was performed using an avidinbiotin complex method and monoclonal antibodies against E-cad and EGFR. Unequivocal membrane staining in 410% of tumor cells was considered as a positive expression of E-cad and EGFR. Markers expression and coexpression were analyzed against clinicopathologic variables (age, gender, smoking status, performance status, weight loss, histology, grade, stage, and lymph node involvement) and patient survival. There were 118, 126, and 115 cases that were fully assessable for E-cad, EGFR, and both markers, respectively. For E-cad, 65 cases (55%) were positive ( þ ), 53 (45%) were negative (À); 23 cases of the negative group had only cytoplasmic staining. For EGRF, 43 cases (34%) were ( þ ), and 83 (66%) were (À). There was no significant association between E-cad or EGFR, and any of the clinicopathologic variables except for an association between EGFR( þ ) and SCC histologic type. Both negative and cytoplasmic staining of E-cad correlated with shorter patient survival with P ¼ 0.008 and 0.002, respectively. EGFR expression did not correlate with patient survival; however, patients with E-cad(À)/EGFR( þ ) phenotype had poorer survival than those with E-cad( þ )/EGFR(À) (P ¼ 0.026). Our study suggests that lung AdC and SCC may be stratified based on expression of E-cad and EGFR with the E-cad(À)/EGFR( þ ) expression having a worse disease outcome. Moreover, the cytoplasmic expression of E-cad may represent an altered localization of this protein in association with tumorigenicity.

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“…More importantly, EGFR expression in human breast tumours has been correlated with a poor prognosis (Perez et al, 1984;Sainsbury et al, 1985;Received 17April 1996Revised 7 August 1996 Accepted 8 August 1996 Correspondence to: R Perez and F-D Bohmer Macias et al, 1986Macias et al, , 1987aKlijn et al, 1992), and a link between EGFR activity and the malignant process has also been suggested for a number of other epithelial tumours, including non-small-cell lung cancer (NSCLC) (Khazaie et al, 1993;Modjtahedi and Dean, 1994;Fontanini et al, 1995). Therefore, the evaluation of the EGF/EGFR system as a potential target for tumour therapy is highly warranted (Baselga and Mendelsohn, 1994a;Modjtahedi and Dean, 1994).…”

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confidence: 99%

Growth inhibition of human lung adenocarcinoma cells by antibodies against epidermal growth factor receptor and by ganglioside GM3: involvement of receptor-directed protein tyrosine phosphatase(s)

Pestana

Greiser²,

Sánchez³

et al. 1997

Br J Cancer

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Summary Growth of the EGF receptor-expressing non-small-cell lung carcinoma cell line H125 seems to be at least partially driven by autocrine activation of the resident EGF receptors. Thus, the possibility of an EGF receptor-directed antiproliferative treatment was investigated in vitro using a monoclonal antibody (cxEGFR ior egf/r3) against the human EGF receptor and gangliosides which are known to possess antiproliferative and anti-tyrosine kinase activity. The moderate growth-inhibitory effect of aEGFR ior egf/r3 was strongly potentiated by the addition of monosialoganglioside G M3 Likewise, the combination of aEGFR ior egf/r3 and GM3 inhibited EGF receptor autophosphorylation activity in Hi 25 cells more strongly than either agent alone. A synergistic inhibition of EGF receptor autophosphorylation by aEGFR ior egf/r3 and GM3 was also observed in the human epidermoid carcinoma cell line A431. In both cell lines, the inhibition of EGF receptor autophosphorylation by GM3 was prevented by pretreatment of the cells with pervanadate, a potent inhibitor of protein tyrosine phosphatases (PTPases). Also, GM3 accelerated EGF receptor dephosphorylation in isolated A431 cell membranes. These findings indicate that GM3 has the capacity to activate EGF receptor-directed PTPase activity and suggest a novel possible mechanism for the regulation of cellular PTPases.

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Epidermal growth factor receptor (EGFr) expression in non-small cell lung carcinomas correlates with metastatic involvement of hilar and mediastinal lymph nodes in the squamous subtype

Cited by 115 publications

References 28 publications

Prognostic Values of Stromal Proportion and PCNA, Ki-67, and p53 Proteins in Patients with Resected Adenocarcinoma of the Lung

Prognostic Values of Stromal Proportion and PCNA, Ki-67, and p53 Proteins in Patients with Resected Adenocarcinoma of the Lung

Altered E-cadherin and epidermal growth factor receptor expressions are associated with patient survival in lung cancer: a study utilizing high-density tissue microarray and immunohistochemistry

Growth inhibition of human lung adenocarcinoma cells by antibodies against epidermal growth factor receptor and by ganglioside GM3: involvement of receptor-directed protein tyrosine phosphatase(s)

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