Genetic and Expression Analysis of HER-2 and EGFR Genes in Salivary Duct Carcinoma: Empirical and Therapeutic Significance

作者: Michelle D. Williams , Dianna B. Roberts , Merrill S. Kies , Li Mao , Randal S. Weber

DOI: 10.1158/1078-0432.CCR-09-0238

关键词:

摘要: Purpose: Salivary duct carcinoma overexpresses epidermal growth factor receptor (EGFR) and HER-2, although the underlying mechanisms remain undefined. Because of potential utilization these markers as treatment targets, we evaluated protein gene status by several techniques to determine complementary value. Experimental Design: A tissue microarray 66 salivary carcinomas was used for immunohistochemical analysis HER-2 EGFR expression (semiquantitatively into a three-tiered system), fluorescence in situ hybridization copy number, chromosomes 7 17 ploidy status. Sequencing exons 18, 19, 21 mutations carried out. Result: For , 46 (69.7%) tumors showed some form (17 at 3+, 2+, 12 1+) but none amplification. Five (9.4%) 53 exon 18 ( n = 3) 19 2). Polysomy chromosome (average >2.5 copies/cell) detected 15 (25.0%) 60 (6 5 2 1+, 0+ expression) correlated with poor 3-year survival P 0.015). (25.8%) expressed (10 3 4 1+). Eight amplification 1 expression). Chromosome polysomy found 8 (15.7%) 51 tumors; two had (3+, Conclusion: Our study shows that ) harbor subset may guide therapy, b pursue an aggressive clinical course cases high expression, c be selected targeted therapy. Clin Cancer Res; 16(8); 2266–74. ©2010 AACR.

参考文章(50)
Klein Hj, Hübner G, Kleinsasser O, Salivary duct carcinoma. A group of salivary gland tumors analogous to mammary duct carcinoma European Archives of Oto-rhino-laryngology. ,vol. 192, pp. 100- ,(1968)
J A Fletcher, J S Ross, HER-2/neu (c-erb-B2) gene and protein in breast cancer. American Journal of Clinical Pathology. ,vol. 112, ,(1999)
T Ettl, S Schwarz, N Kleinsasser, A Hartmann, T E Reichert, O Driemel, Overexpression of EGFR and absence of C-KIT expression correlate with poor prognosis in salivary gland carcinomas Histopathology. ,vol. 53, pp. 567- 577 ,(2008) , 10.1111/J.1365-2559.2008.03159.X
Leon Barnes, Uma Rao, Lydia Contis, John Krause, Ann Schwartz, Philip Scalamogna, Salivary duct carcinoma. Part II. Immunohistochemical evaluation of 13 cases for estrogen and progesterone receptors, cathepsin D, and c-erbB-2 protein. Oral Surgery, Oral Medicine, Oral Pathology. ,vol. 78, pp. 74- 80 ,(1994) , 10.1016/0030-4220(94)90120-1
Leon Barnes, Uma Rao, John Krause, Lydia Contis, Ann Schwartz, Philip Scalamogna, Salivary duct carcinoma: Part I. A clinicopathologic evaluation and DNA image analysis of 13 cases with review of the literature Oral Surgery, Oral Medicine, Oral Pathology. ,vol. 78, pp. 64- 73 ,(1994) , 10.1016/0030-4220(94)90119-8
Michael Jaehne, Kerstin Roeser, Thorsten Jaekel, Jan David Schepers, Natalie Albert, Thomas Löning, Clinical and immunohistologic typing of salivary duct carcinoma Cancer. ,vol. 103, pp. 2526- 2533 ,(2005) , 10.1002/CNCR.21116
Samuel K. Chan, Mark E. Hill, William J. Gullick, The Role of the Epidermal Growth Factor Receptor in Breast Cancer Journal of Mammary Gland Biology and Neoplasia. ,vol. 11, pp. 3- 11 ,(2006) , 10.1007/S10911-006-9008-2
Jason T. Lewis, Rhett P. Ketterling, Kevin C. Halling, Carol Reynolds, Robert B. Jenkins, Daniel W. Visscher, Analysis of intratumoral heterogeneity and amplification status in breast carcinomas with equivocal (2+) HER-2 immunostaining. American Journal of Clinical Pathology. ,vol. 124, pp. 273- 281 ,(2005) , 10.1309/J9VXABUGKC4Y07DL
Anna M. Bofin, Borgny Ytterhus, Cara Martin, John J. O’Leary, Bjørn M. Hagmar, Detection and quantitation of HER-2 gene amplification and protein expression in breast carcinoma. American Journal of Clinical Pathology. ,vol. 122, pp. 110- 119 ,(2004) , 10.1309/8A2DJFT07NE6EWHE
Federico Cappuzzo, Fred R. Hirsch, Elisa Rossi, Stefania Bartolini, Giovanni L. Ceresoli, Lynne Bemis, Jerry Haney, Samir Witta, Kathleen Danenberg, Irene Domenichini, Vienna Ludovini, Elisabetta Magrini, Vanesa Gregorc, Claudio Doglioni, Angelo Sidoni, Maurizio Tonato, Wilbur A. Franklin, Lucio Crino, Paul A. Bunn, Marileila Varella-Garcia, Epidermal Growth Factor Receptor Gene and Protein and Gefitinib Sensitivity in Non–Small-Cell Lung Cancer Journal of the National Cancer Institute. ,vol. 97, pp. 643- 655 ,(2005) , 10.1093/JNCI/DJI112