EGFR overexpression in malignant pleural mesothelioma - An immunohistochemical and molecular study with clinico-pathological correlations

被引:119
作者
Destro, A
Ceresoli, GL
Falleni, M
Zucali, PA
Morenghi, E
Bianchi, P
Pellegrini, C
Cordani, N
Vaira, V
Alloisio, M
Rizzi, A
Bosari, S
Roncalli, M
机构
[1] Univ Milan, Dept Pathol, IRCCS, Ist Clin Humanitas, I-20089 Milan, Italy
[2] IRCCS, Ist Clin Humanitas, Genet Mol Lab, I-20089 Milan, Italy
[3] IRCCS, Ist Clin Humanitas, Dept Oncol, I-20089 Milan, Italy
[4] Osped Maggiore Policlin, Fdn IRCCS, I-20142 Milan, Italy
[5] IRCCS, Ist Clin Humanitas, Clin Trial Off, I-20089 Milan, Italy
[6] Humanitas Gavazzeni, Dept Thorac Surg, I-24125 Bergamo, Italy
关键词
mesothelioma; EGFR; immunohistochemistry; real-time PCR; prognostic factors;
D O I
10.1016/j.lungcan.2005.10.016
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The epidermal growth factor receptor (EGFR) is overexpressed in many epithelial malignancies, against which some antitumoral drugs have been developed. There is a lack of information as to EGFR expression in malignant pleural mesothelioma (MPM), an aggressive and fatal cancer poorly responsive to current oncotogical treatments. Our aim was to: (a) compare EGFR immunohistochemical expression with mRNA levels measured by real time PCR; (b) assess the relationships between EGFR expression and clinico-pathologicat data including survival; (c) analyze the EGFR mutations. We developed an immunohistochemical method of EGFR evaluation based on the number of immunoreactive cells and staining intensity in 61 MPMs. EGFR immunoreactivity was documented in 34/61 (55.7%) cases. A significant correlation between EGFR protein and mRNA levels (p=0.0077) was found, demonstrating the reliability of our quantification method of EGFR membrane expression. Radically resected patients (p = 0.005) and those with epithelial histotype (p = 0.048) showed an increased survival. No statistical correlation between EGFR immunoreactivity and patients survival was observed. No EGFR mutation was documented. This study documents EGFR overexpression in MPM at the protein and the transcriptional levels; it proposes a reliabte method for EGFR expression evaluation in MPM. EGFR levels are not associated with chnico-pathological features of patients, including survival. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:207 / 215
页数:9
相关论文
共 36 条
[31]   Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: Results in 183 patients [J].
Sugarbaker, DJ ;
Flores, RM ;
Jaklitsch, MT ;
Richards, WG ;
Strauss, GM ;
Carson, JM ;
DeCamp, MM ;
Swanson, SJ ;
Bueno, R ;
Lukanich, JM ;
Baldini, EH ;
Mentzer, SJ .
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY, 1999, 117 (01) :54-63
[32]  
Travis W., 1999, Histological Typing of Lung and Pleural Tumours
[33]   Pleural mesothelioma: little evidence, still time to do trials [J].
Treasure, T ;
Sedrakyan, A .
LANCET, 2004, 364 (9440) :1183-1185
[34]   Diffuse malignant mesothelioma of the peritoneum and pleura, analysis of markers [J].
Trupiano, JK ;
Geisinger, KR ;
Willingham, MC ;
Manders, P ;
Zbieranski, N ;
Case, D ;
Levine, EA .
MODERN PATHOLOGY, 2004, 17 (04) :476-481
[35]   Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes [J].
Vandesompele, Jo ;
De Preter, Katleen ;
Pattyn, Filip ;
Poppe, Bruce ;
Van Roy, Nadine ;
De Paepe, Anne ;
Speleman, Frank .
GENOME BIOLOGY, 2002, 3 (07)
[36]   Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma [J].
Vogelzang, NJ ;
Rusthoven, JJ ;
Symanowski, J ;
Denham, C ;
Kaukel, E ;
Ruffie, P ;
Gatzemeier, U ;
Boyer, M ;
Emri, S ;
Manegold, C ;
Niyikiza, C ;
Paoletti, P .
JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (14) :2636-2644