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
[1]   Pemetrexed (ALIMTA), a novel multitargeted antineoplastic agent [J].
Adjei, AA .
CLINICAL CANCER RESEARCH, 2004, 10 (12) :4276S-4280S
[2]  
Arteaga CL, 2002, ONCOLOGIST, V7, P31
[3]  
Baldini Elizabeth H, 2004, Thorac Surg Clin, V14, P543
[4]  
Brabender J, 2001, CLIN CANCER RES, V7, P1850
[5]  
Cai YC, 2004, ARCH PATHOL LAB MED, V128, P68
[6]   Gefitinib in pretreated non-small-cell lung cancer (NSCLC):: Analysis of efficacy and correlation with HER2 and epidermal growth factor receptor expression in locally advanced or metastatic NSCLC [J].
Cappuzzo, F ;
Gregorc, V ;
Rossi, E ;
Cancellieri, A ;
Magrini, E ;
Paties, CT ;
Ceresoli, G ;
Lombardo, L ;
Bartolini, S ;
Calandri, C ;
De Rosa, M ;
Villa, E ;
Crinò, L .
JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (14) :2658-2663
[7]   Akt phosphorylation and gefitinib efficacy in patients with advanced non-small-cell lung cancer [J].
Cappuzzo, F ;
Magrini, E ;
Ceresoli, GL ;
Bartolini, S ;
Rossi, E ;
Ludovini, V ;
Gregorc, V ;
Ligorio, C ;
Cancellieri, A ;
Damiani, S ;
Spreafico, A ;
Paties, CT ;
Lombardo, L ;
Calandri, C ;
Bellezza, G ;
Tonato, M ;
Crinò, L .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2004, 96 (15) :1133-1141
[8]   Therapeutic outcome according to histologic subtype in 121 patients with malignant pleural mesothelioma [J].
Ceresoli, GL ;
Locati, LD ;
Ferreri, AJM ;
Cozzarini, C ;
Passoni, P ;
Melloni, G ;
Zannini, P ;
Bolognesi, A ;
Villa, E .
LUNG CANCER, 2001, 34 (02) :279-287
[9]   MALIGNANT PLEURAL MESOTHELIOMA AND EPIDERMAL GROWTH-FACTOR RECEPTOR (EGF-R) - RELATIONSHIP OF EGF-R WITH HISTOLOGY AND SURVIVAL USING FIXED PARAFFIN EMBEDDED TISSUE AND THE F4, MONOCLONAL-ANTIBODY [J].
DAZZI, H ;
HASLETON, PS ;
THATCHER, N ;
WILKES, S ;
SWINDELL, R ;
CHATTERJEE, AK .
BRITISH JOURNAL OF CANCER, 1990, 61 (06) :924-926
[10]   THE EPIDERMAL GROWTH-FACTOR RECEPTOR AS A PROGNOSTIC MARKER - RESULTS OF 370 PATIENTS AND REVIEW OF 3009 PATIENTS [J].
FOX, SB ;
SMITH, K ;
HOLLYER, J ;
GREENALL, M ;
HASTRICH, D ;
HARRIS, AL .
BREAST CANCER RESEARCH AND TREATMENT, 1994, 29 (01) :41-49