Epidermal growth factor receptor expression and gene amplification in colorectal carcinoma:: an immunohistochemical and chromogenic in situ hybridization study

被引:122
作者
Shia, J
Klimstra, DS
Li, AR
Qin, J
Saltz, L
Teruya-Feldstein, J
Akram, M
Chung, KY
Yao, D
Paty, PB
Gerald, W
Chen, BY
机构
[1] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA
[2] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA
[3] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA
[4] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA
关键词
cetuximab; anti-EGFR therapy; gene amplification;
D O I
10.1038/modpathol.3800417
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Recent data suggest that detection of epidermal growth factor receptor protein by immunohistochemistry ( IHC) does not predict response to the antiepidermal growth factor receptor drug, cetuximab, in patients with colorectal carcinoma. In searching for foundation for further investigation to optimize patient selection for cetuximab therapy, this study sought to exploit the tissue microarray and chromogenic in situ hybridization techniques to evaluate the status of epidermal growth factor receptor gene amplification in colorectal cancer and its relationship with protein expression by IHC. The study included 158 primary or metastatic colorectal adenocarcinomas. Immunohistochemical results were scored as 0 - 3 + based on the intensity of membrane staining. The in situ hybridization signals were counted in 30 nuclei per tissue core. Overall, the rate of tissue loss was 7%, yielding 147 analyzable cases: 123 primary, 24 metastatic. Positive immunohistochemical staining of any intensity was detected in 85% ( 105/ 123) of primary and 79% ( 19/ 24) of metastatic tumors, whereas gene amplification ( 45 gene copies/ nucleus) was only seen in 12% ( 15/ 123) of primary and 8% ( 2/ 24) of metastatic tumors. Only 2/ 15 primary and 1/ 2 metastatic tumors that showed gene amplification were amplified at a high level ( 410 gene copies/ nucleus). Although a positive correlation was detected between the intensity of protein expression and the likelihood of gene amplification in both the primary ( P = 0.01) and the metastatic ( P = 0.05) tumors, IHC had a low specificity ( 17% in primary, 23% in metastatic) in predicting gene amplification. Conversely, all tumors that did not express the protein by IHC lacked gene amplification. Thus, this study shows that only a small fraction of epidermal growth factor receptor- positive colorectal carcinomas detected by IHC are associated with gene amplification. Additional studies are needed to determine whether epidermal growth factor receptor gene amplification bears any informative value in predicting response to cetuximabbased therapy.
引用
收藏
页码:1350 / 1356
页数:7
相关论文
共 36 条
[21]   Tissue microarrays for high-throughput molecular profiling of tumor specimens [J].
Kononen, J ;
Bubendorf, L ;
Kallioniemi, A ;
Bärlund, M ;
Schraml, P ;
Leighton, S ;
Torhorst, J ;
Mihatsch, MJ ;
Sauter, G ;
Kallioniemi, OP .
NATURE MEDICINE, 1998, 4 (07) :844-847
[22]   Color multiplex polymerase chain reaction for quantitative analysis of epidermal growth factor receptor genes in colorectal adenocarcinorna [J].
Layfield, LJ ;
Bernard, PS ;
Goldstein, NS .
JOURNAL OF SURGICAL ONCOLOGY, 2003, 83 (04) :227-231
[23]  
LENZ HJ, 2004, P AM SOC CLIN ONC NE
[24]   Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib [J].
Lynch, TJ ;
Bell, DW ;
Sordella, R ;
Gurubhagavatula, S ;
Okimoto, RA ;
Brannigan, BW ;
Harris, PL ;
Haserlat, SM ;
Supko, JG ;
Haluska, FG ;
Louis, DN ;
Christiani, DC ;
Settleman, J ;
Haber, DA .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 350 (21) :2129-2139
[25]   Chromogenic in situ hybridization (CISH):: a novel alternative in screening archival breast cancer tissue samples for HER-2/neu status [J].
Madrid, MA ;
Lo, RW .
BREAST CANCER RESEARCH, 2004, 6 (05) :R593-R600
[26]   Evaluation of epidermal growth factor receptor (EGFR) by chromogenic in situ hybridization (CISH™) and immunohistochemistry (IHC) in archival gliomas using bright-field microscopy [J].
Marquez, A ;
Wu, R ;
Zhao, JX ;
Tao, JH ;
Shi, ZR .
DIAGNOSTIC MOLECULAR PATHOLOGY, 2004, 13 (01) :1-8
[27]   Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer [J].
Mendelsohn, J ;
Baselga, J .
JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (14) :2787-2799
[28]   Her 2/neu expression and gene amplification in colon cancer [J].
Nathanson, DR ;
Culliford, AT ;
Shia, J ;
Chen, BY ;
D'Alessio, M ;
Zeng, ZS ;
Nash, GM ;
Gerald, W ;
Barany, F ;
Paty, PB .
INTERNATIONAL JOURNAL OF CANCER, 2003, 105 (06) :796-802
[29]   EGFR and cancer prognosis [J].
Nicholson, RI ;
Gee, JMW ;
Harper, ME .
EUROPEAN JOURNAL OF CANCER, 2001, 37 :S9-S15
[30]   Protein overexpression and gene amplification of HER-2 and EGFR in colorectal cancers:: an immunohistochemical and fluorescent in situ hybridization study [J].
Ooi, A ;
Takehana, T ;
Li, XL ;
Suzuki, S ;
Kunitomo, K ;
Iino, H ;
Fujii, H ;
Takeda, Y ;
Dobashi, Y .
MODERN PATHOLOGY, 2004, 17 (08) :895-904