EGFR in gastric carcinomas: prognostic significance of protein overexpression and high gene copy number

被引:247
作者
Kim, M. A. [1 ]
Lee, H. S. [2 ]
Lee, H. E. [1 ]
Jeon, Y. K. [1 ]
Yang, H. K. [3 ,4 ]
Kim, W. H. [1 ,4 ]
机构
[1] Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 110799, South Korea
[2] Seoul Natl Univ, Bundang Hosp, Dept Pathol, Gyeonggi, South Korea
[3] Seoul Natl Univ, Coll Med, Dept Surg, Seoul 110799, South Korea
[4] Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul 110799, South Korea
关键词
epidermal growth factor receptor; gene amplification; stomach neoplasm; survival analysis; tissue array analysis;
D O I
10.1111/j.1365-2559.2008.03021.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Aims: Epidermal growth factor receptor (EGFR) expression has been observed in a variety of solid tumours with the potential of new targeted therapeutic agents. The aim was to evaluate the EGFR status of gastric carcinoma (GC) using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Methods and results: The EGFR status was evaluated in GC tissues from 511 patients using IHC and FISH. In addition, the clinicopathological characteristics were examined and the results were compared with the EGFR status. One hundred and forty cases (27.4%) showed EGFR overexpression by IHC. EGFR overexpression was associated with older age (P = 0.001), moderately or poorly differentiated histology (P = 0.001) and higher stage disease (P = 0.046). Sixteen cases (3.1%) showed high polysomy and 12 cases (2.3%) had gene amplification by FISH. The correlation between IHC and FISH results was statistically significant (P < 0.001). The patients with GC who had EGFR overexpression had an unfavourable prognosis and multivariate analysis showed that EGFR overexpression was a possible independent unfavourable prognostic factor. Conclusions: EGFR overexpression was observed in a subset of cases with GC and was associated with an unfavourable prognosis. It will be important to evaluate EGFR status to interpret future clinical trials properly using EGFR targeted agents.
引用
收藏
页码:738 / 746
页数:9
相关论文
共 29 条
[1]  
Amann J, 2005, CANCER RES, V65, P226
[2]   Critical update and emerging trends in epidermal growth factor receptor targeting in cancer [J].
Baselga, J ;
Arteaga, CL .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (11) :2445-2459
[3]   Comparison of two antibodies for immunohistochemical evaluation of epidermal growth factor receptor expression in colorectal carcinomas, adenomas, and normal mucosa [J].
Bhargava, R ;
Chen, BY ;
Klimstra, DS ;
Saltz, LB ;
Hedvat, C ;
Tang, LH ;
Gerald, W ;
Teruya-Feldstein, J ;
Paty, PB ;
Qin, J ;
Shia, J .
CANCER, 2006, 106 (08) :1857-1862
[4]   Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer [J].
Cappuzzo, F ;
Hirsch, FR ;
Rossi, E ;
Bartolini, S ;
Ceresoli, GL ;
Bemis, L ;
Haney, J ;
Witta, S ;
Danenberg, K ;
Domenichini, I ;
Ludovini, V ;
Magrini, E ;
Gregorc, V ;
Doglioni, C ;
Sidoni, A ;
Tonato, M ;
Franklin, WA ;
Crino, L ;
Bunn, PA ;
Varella-Garcia, M .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2005, 97 (09) :643-655
[5]   Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry [J].
Chung, KY ;
Shia, J ;
Kemeny, NE ;
Shah, M ;
Schwartz, GK ;
Tse, A ;
Hamilton, A ;
Pan, D ;
Schrag, D ;
Schwartz, L ;
Klimstra, DS ;
Fridman, D ;
Kelsen, DP ;
Saltz, LB .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (09) :1803-1810
[6]   Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer [J].
Cunningham, D ;
Humblet, Y ;
Siena, S ;
Khayat, D ;
Bleiberg, H ;
Santoro, A ;
Bets, D ;
Mueser, M ;
Harstrick, A ;
Verslype, C ;
Chau, I ;
Van Cutsem, E .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 351 (04) :337-345
[7]   Phase II trial of erlotinib in gastroesophageal junction and gastric adenocarcinomas: SWOG 0127 [J].
Dragovich, Tomislav ;
McCoy, Sheryl ;
Fenoglio-Preiser, Cecilia M. ;
Wang, Jiang ;
Benedetti, Jacqueline K. ;
Baker, Amanda F. ;
Hackett, Christopher B. ;
Urba, Susan G. ;
Zaner, Ken S. ;
Blanke, Charles D. ;
Abbruzzese, James L. .
JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (30) :4922-4927
[8]   Epidermal growth factor receptor in non-small-cell lung carcinomas:: Correlation between gene copy number and protein expression and impact on prognosis [J].
Hirsch, FR ;
Varella-Garcia, M ;
Bunn, PA ;
Di Maria, MV ;
Veve, R ;
Bremnes, RM ;
Barón, AE ;
Zeng, C ;
Franklin, WA .
JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (20) :3798-3807
[9]   Gastric cancer [J].
Hohenberger, P ;
Gretschel, S .
LANCET, 2003, 362 (9380) :305-315
[10]   GENE AMPLIFICATION AND OVEREXPRESSION OF EGF RECEPTOR IN SQUAMOUS-CELL CARCINOMAS OF THE HEAD AND NECK [J].
ISHITOYA, J ;
TORIYAMA, M ;
OGUCHI, N ;
KITAMURA, K ;
OHSHIMA, M ;
ASANO, K ;
YAMAMOTO, T .
BRITISH JOURNAL OF CANCER, 1989, 59 (04) :559-562