PMID- 34095900 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220813 VI - 4 IP - 3 DP - 2021 Dec TI - Impact of Using Median vs. Mean in Calculating ERBB2 FISH Results in Breast Cancer. PG - 87-96 AB - INTRODUCTION: Erb-b2 receptor tyrosine kinase 2 (ERBB2) testing is used to measure the status of ERBB2 gene expression and DNA amplification. Test results have been reported with a discrepancy as high as 20%. The purpose of this study was to improve ERBB2 fluorescence in situ hybridization (FISH) sensitivity by evaluating results generated by median as well as mean calculations. METHODS: We retrospectively identified breast cancer cases at our institution in which ERBB2 FISH testing was performed in-house from June 2018 to May 2020. FISH results were classified using the 2018 American Society of Clinical Oncology/College of American Pathologists guidelines: groups 1 and 5 are FISH positive and negative, respectively, and groups 2-4 are equivocal requiring additional work-up. FISH counting sheets were collected and regrouped by median ERBB2 copy number counts and median ERBB2/CEP17 ratio and compared with the mean ERBB2 and mean ERBB2/CEP17 ratio. Intra-tumor genetic heterogeneity and CEP17 copy number gain (CEP17 >/=3) were assessed to see if they affect the discrepancy between median and mean groups. RESULTS: Seventy-two breast cancer cases were collected and evaluated. Eleven cases (11 of 72 [15%]) had discrepant grouping by mean and median calculations. A significant number of discrepancies were found for CEP17 copy number gain (p = 0.027) but not for ERBB2 (p = 0.411), the ERBB2/CEP17 ratio (p = 0.445), FISH results (p = 0.194), or genetic heterogeneity (p = 0.465). Among the four cases regrouped to median group 1, 2 were from mean group 3 and underwent anti-ERBB2 targeted therapy and 2 were from mean groups 4 and 5 may have benefitted from targeted therapy with more than 30% amplified cells. The median may be better to reflect the monosomy subclone within tumor tissues for the case 387 moved from mean group 5 to median group 2. The 6 cases moved from mean group 5 to median group 4 with CEP17 copy number gain may have had a poor prognosis based on other study result. CONCLUSION: Including the median calculation may increase ERBB2 sensitivity and identification of CEP17 copy number gain. Further clinical studies are necessary to examine the outcome of including median in calculating ERBB2/CEP17 values. FAU - Song, Jie AU - Song J AD - Program in Diagnostic Genetics and Genomics, School of Health Professions, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. FAU - Yu, Alexander AU - Yu A AD - School of Medicine, The University of Texas Medical Branch, Galveston, Texas, USA. FAU - Munoz, Diana AU - Munoz D AD - Health Information Management, Houston Methodist, Houston, Texas, USA. FAU - Han, Song AU - Han S AD - Department of Pathology, The University of Texas Medical Branch, Galveston, Texas, USA. FAU - Nimmakayalu, Manjunath AU - Nimmakayalu M AD - Program in Diagnostic Genetics and Genomics, School of Health Professions, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. FAU - Hu, Peter C AU - Hu PC AD - Program in Diagnostic Genetics and Genomics, School of Health Professions, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. FAU - Dong, Jianli AU - Dong J AD - Department of Pathology, The University of Texas Medical Branch, Galveston, Texas, USA. LA - eng GR - TL1 TR001440/TR/NCATS NIH HHS/United States PT - Journal Article DEP - 20210415 PL - India TA - Cancer Med J JT - Cancer medicine journal JID - 101744997 PMC - PMC8171267 MID - NIHMS1695277 OTO - NOTNLM OT - Breast cancer OT - CEP17 OT - ERBB2 OT - FISH OT - Mean OT - Median EDAT- 2021/06/08 06:00 MHDA- 2021/06/08 06:01 PMCR- 2021/12/01 CRDT- 2021/06/07 06:15 PHST- 2021/06/07 06:15 [entrez] PHST- 2021/06/08 06:00 [pubmed] PHST- 2021/06/08 06:01 [medline] PHST- 2021/12/01 00:00 [pmc-release] PST - ppublish SO - Cancer Med J. 2021 Dec;4(3):87-96. Epub 2021 Apr 15.