PMID- 23154768 OWN - NLM STAT- MEDLINE DCOM- 20130121 LR - 20191210 IS - 1532-0979 (Electronic) IS - 0147-5185 (Linking) VI - 36 IP - 12 DP - 2012 Dec TI - Silver-enhanced in situ hybridization for determination of EGFR copy number alterations in non-small cell lung cancer. PG - 1801-8 LID - 10.1097/PAS.0b013e31826ff153 [doi] AB - Epidermal growth factor receptor (EGFR) gene mutation and high gene copy number (CN) predict response to EGFR tyrosine kinase inhibitor therapy in the adenocarcinoma subtype of non-small cell lung cancer (NSCLC). The aims of this study were first to compare automated enzyme metallographic silver-enhanced in situ hybridization (SISH) with conventionally used fluorescence in situ hybridization (FISH) in the determination of EGFR CN in NSCLC tissue sections, and second to assess the association of EGFR CN with EGFR mutations and clinicopathological parameters. FISH and SISH were performed on tissue microarrays and large sections. Samples from 56 consecutively surgically resected NSCLC patients (cohort 1) and from 60 selected lung adenocarcinoma patients (cohort 2) were analyzed. EGFR CN was classified applying the Colorado criteria, and agreement between both methods was evaluated using kappa values. EGFR CN was compared with EGFR protein expression and EGFR gene mutations. The results of SISH and FISH were identical in 114 of the 116 cases examined using the 2 techniques. One case was FISH+, SISH-, and 1 case was FISH- and SISH+. The agreement between the 2 methods was good in cohort 1 (kappa=0.642 [0.428, 0.823]) and excellent in cohort 2 (kappa=0.963 [0.870, 1.000]). EGFR positivity by FISH and SISH was associated with high EGFR protein expression (P<0.001) and EGFR mutation (P<0.001). These results validate the use of SISH for assessing EGFR CN alterations in NSCLC. The advantage of a permanent result and the possibility of bright-field microscopy make SISH an attractive alternative to FISH. FAU - Wulf, Marie-Angela AU - Wulf MA AD - Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland. FAU - Bode, Beata AU - Bode B FAU - Zimmermann, Dieter AU - Zimmermann D FAU - Rufibach, Kaspar AU - Rufibach K FAU - Weder, Walter AU - Weder W FAU - Moch, Holger AU - Moch H FAU - Soltermann, Alex AU - Soltermann A FAU - Tischler, Verena AU - Tischler V LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Validation Study PL - United States TA - Am J Surg Pathol JT - The American journal of surgical pathology JID - 7707904 RN - 0 (Acetates) RN - 0 (Biomarkers, Tumor) RN - 0 (Silver Compounds) RN - 19PPS85F9H (silver acetate) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - *Acetates MH - Aged MH - Automation, Laboratory MH - Biomarkers, Tumor/analysis/*genetics MH - Carcinoma, Non-Small-Cell Lung/enzymology/*genetics/pathology MH - *DNA Copy Number Variations MH - DNA Mutational Analysis MH - ErbB Receptors/analysis/*genetics MH - Female MH - *Gene Dosage MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization/*methods MH - In Situ Hybridization, Fluorescence MH - Lung Neoplasms/enzymology/*genetics/pathology MH - Male MH - Middle Aged MH - Mutation MH - Predictive Value of Tests MH - Reproducibility of Results MH - *Silver Compounds MH - Tissue Array Analysis EDAT- 2012/11/17 06:00 MHDA- 2013/01/23 06:00 CRDT- 2012/11/17 06:00 PHST- 2012/11/17 06:00 [entrez] PHST- 2012/11/17 06:00 [pubmed] PHST- 2013/01/23 06:00 [medline] AID - 00000478-201212000-00007 [pii] AID - 10.1097/PAS.0b013e31826ff153 [doi] PST - ppublish SO - Am J Surg Pathol. 2012 Dec;36(12):1801-8. doi: 10.1097/PAS.0b013e31826ff153.