PMID- 16648870 OWN - NLM STAT- MEDLINE DCOM- 20070808 LR - 20230210 IS - 0893-3952 (Print) IS - 0893-3952 (Linking) VI - 19 IP - 7 DP - 2006 Jul TI - Expression of epidermal growth factor receptor in squamous cell carcinomas of the anal canal is independent of gene amplification. PG - 942-9 AB - Immunohistochemical detection of expression of the epidermal growth factor receptor (EGFR) has been utilized to identify eligible patients with solid malignant tumors, including colorectal adenocarcinoma, for monoclonal antibody therapy (eg, cetuximab). The EGFR status in squamous cell carcinoma of the anal canal, an uncommon malignancy traditionally treated with chemoradiation, has not been well investigated. In this study, 38 primary squamous cell carcinomas of the anal canal were immunohistochemically examined for EGFR expression and analyzed by fluorescence in situ hybridization (FISH) for EGFR gene copy numbers. The results showed a variable degree of EGFR expression in 21 (55%) tumors, among which 13 (62%) cases exhibited a 2+ to 3+ staining pattern according to the Dako EGFR phamDx interpretation guide. There were no significant differences among tumors stratified by stage, degree of keratinization, or tissue block storage times. FISH analysis showed that none of the 34 cases with interpretable results had EGFR gene amplification. Increased gene copy numbers due to polysomy 7 were seen in seven of 18 (39%) cases that expressed EGFR protein and four of 16 (25%) cases that did not (P=0.3876). Ten (56%) tumors with positive EGFR staining showed a balanced disomy 7 pattern and one case with monosomy 7 exhibited strong EGFR expression (3+). These results demonstrate that EGFR is overexpressed in more than one-half of the squamous cell carcinomas of the anal canal through mechanisms other than gene amplification. These observations may have important therapeutic implications since EGFR-based targeted therapies have shown promise for other malignant neoplasms. FAU - Alvarez, Gustavo AU - Alvarez G AD - Lauren V Ackerman Laboratory of Surgical Pathology, Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110-1093, USA. FAU - Perry, Arie AU - Perry A FAU - Tan, Benjamin R AU - Tan BR FAU - Wang, Hanlin L AU - Wang HL LA - eng PT - Journal Article DEP - 20060428 PL - United States TA - Mod Pathol JT - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc JID - 8806605 RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Anus Neoplasms/genetics/*metabolism/pathology MH - Carcinoma, Squamous Cell/genetics/*metabolism/pathology MH - ErbB Receptors/genetics/*metabolism MH - Female MH - Gene Amplification MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Male MH - Middle Aged MH - Retrospective Studies MH - *Up-Regulation EDAT- 2006/05/02 09:00 MHDA- 2007/08/09 09:00 CRDT- 2006/05/02 09:00 PHST- 2006/05/02 09:00 [pubmed] PHST- 2007/08/09 09:00 [medline] PHST- 2006/05/02 09:00 [entrez] AID - S0893-3952(22)03351-8 [pii] AID - 10.1038/modpathol.3800608 [doi] PST - ppublish SO - Mod Pathol. 2006 Jul;19(7):942-9. doi: 10.1038/modpathol.3800608. Epub 2006 Apr 28.