Differential expression of the epidermal growth factor receptor and its ligands in primary non-small cell lung cancers and adjacent benign lung Journal Article

  

Authors:	Rusch, V.; Baselga, J.; Cordon-Cardo, C.; Orazem, J.; Zaman, M.; Hoda, S.; McIntosh, J.; Kurie, J.; Dmitrovsky, E.
Article Title:	Differential expression of the epidermal growth factor receptor and its ligands in primary non-small cell lung cancers and adjacent benign lung
Abstract:	The epidermal growth factor receptor (EGFR) and one of its ligands, transforming growth factor α (TGF-α), are thought to function as a potential autocrine loop in non-small cell lung cancer (NSCLC). However, the expression pattern of EGFR and the TGF-α-related ligands have not been fully characterized in primary NSCLC and adjacent benign lung tissue. For this reason, we comprehensively examined the coexpression and differential expression of EGFR and its ligands, TGF-α, epidermal growth factor (EGF), and amphiregulin (AR), by Northern analysis, in paired samples of primary tumors and uninvolved lung. For those RNA species overexpressed in malignant lung, single cell expression patterns were studied by immunohistochemistry. Specimens were obtained from 57 consecutive patients who underwent resection of carefully staged resectable NSCLC and were followed prospectively. Most (112 of 114) tissue samples yielded high-quality RNA. EGFR was expressed in 82 of 88 (93%) tissue samples, while TGF-α was expressed in 62 of 72 (86%) samples, and AR was expressed in 64 of 70 (92%) samples. EGF was unexpressed in total cellular RNA in both tumor and uninvolved lung. In a comparison of RNA expression patterns in tumors and uninvolved lung, overexpression of EGFR was found in 45% (22 of 44) of tumors, while overexpression of TGF-α was seen in 61 % (22 of 36) of tumors, and decreased expression of AR was seen in 63% (22 of 35) of tumors. Cell type and stage did not influence differential expression, indicating that this is a frequent event in primary NSCLC. Simultaneous overexpression of EGFR and TGF-α was seen in only 38% of tumors. Simultaneous overexpression of EGFR and decreased expression of AR were seen in only 21 % of tumors. Thus far, the differential expression of EGFR, TGF-α, and AR does not correlate with either disease-free or overall survival. These findings indicate that histologically dissimilar tumors can express similar components of autocrine or paracrine growth factor loops. Differential expression of EGFR and its ligands in tumor specimens compared to uninvolved lung is a common event in NSCLC and may participate in tumor growth without necessarily influencing tumor progression or histology. © 1993, American Association for Cancer Research. All rights reserved.
Keywords:	immunohistochemistry; epidermal growth factor; adult; cancer survival; controlled study; human tissue; aged; human cell; major clinical study; histopathology; comparative study; follow-up studies; neoplasm staging; prospective studies; adenocarcinoma; gene expression; lung non small cell cancer; carcinoma, non-small-cell lung; lung neoplasms; epidermal growth factor receptor; receptor, epidermal growth factor; rna; lung; transforming growth factors; ligands; blotting, northern; glycoproteins; amphiregulin; transforming growth factor alpha; northern blotting; growth substances; middle age; receptor upregulation; human; male; female; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.
Journal Title:	Cancer Research
Volume:	53
Issue:	10
ISSN:	0008-5472
Publisher:	American Association for Cancer Research
Date Published:	1993-05-15
Start Page:	2379
End Page:	2385
Language:	English
PUBMED:	7683573
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0027159063&partnerID=40&md5=bce0033f9aa7b04fc79b7f03ea239cf7
Notes:	Source: Scopus

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