Differential expression of the epidermal growth factor receptor and its ligands in primary non-small cell lung cancers and adjacent benign lung.
Differential expression of the epidermal growth factor receptor and its ligands in primary non-small cell lung cancers and adjacent benign lung.
复制标题
DOI：
--
复制
发表时间：
1993-05
期刊：
影响因子：
11.2
通讯作者：
V. Rusch;J. Baselga;C. Cordon-Cardo;J. Orazem;M. Zaman;S. Hoda;J. McIntosh;J. Kurie;E. Dmitrovsky
中科院分区：
文献类型：
--
作者：
V. Rusch;J. Baselga;C. Cordon-Cardo;J. Orazem;M. Zaman;S. Hoda;J. McIntosh;J. Kurie;E. Dmitrovsky
表皮生长因子受体（EGFR）及其配体之一转化生长因子α（TGF-α）被认为在非小细胞肺癌（NSCLC）中起着潜在的自分泌环的作用。然而，EGFR和TGF-α相关配体的表达模式在原发性NSCLC和邻近良性肺组织中尚未完全表征。为此，我们通过北方分析，在原发性肿瘤和未受累肺的配对样本中，全面检测了EGFR及其配体TGF-α、表皮生长因子（EGF）和双调蛋白（AR）的共表达和差异表达。对于那些在恶性肺中过表达的RNA种类，通过免疫组织化学研究单细胞表达模式。样本来自57例连续患者，这些患者接受了仔细分期的可切除NSCLC切除术，并进行了前瞻性随访。大多数（114个中的112个）组织样本产生了高质量的RNA。EGFR在88份组织样本中的82份（93%）中表达，而TGF-α在72份样本中的62份（86%）中表达，AR在70份样本中的64份（92%）中表达。EGF在肿瘤和正常肺组织中均不表达。在肿瘤和未受累肺的RNA表达模式的比较中，在45%（22/44）的肿瘤中发现EGFR过表达，而在61%（22/36）的肿瘤中观察到TGF-α过表达，在63%（22/35）的肿瘤中观察到AR表达降低。细胞类型和分期不影响差异表达，表明这是原发性NSCLC的常见事件。EGFR和TGF-α同时过表达仅见于38%的肿瘤。EGFR同时过表达和AR表达减少仅见于21%的肿瘤。到目前为止，EGFR、TGF-α和AR的差异表达与无病生存期或总生存期无关。这些发现表明，组织学上不同的肿瘤可以表达自分泌或旁分泌生长因子环的相似成分。肿瘤标本中EGFR及其配体与未受累肺组织相比的差异表达是NSCLC中的常见事件，可能参与肿瘤生长，但不一定影响肿瘤进展或组织学。
The epidermal growth factor receptor (EGFR) and one of its ligands, transforming growth factor alpha (TGF-alpha), 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-alpha-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-alpha, 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-alpha 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-alpha 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-alpha 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-alpha, 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.