Impact of Using Median Vs. Mean in Calculating ERBB2 FISH Results in Breast Cancer

Overview

Journal Cancer Med J

Date 2021 Jun 7

PMID 34095900

Authors

Jie Song

Alexander Yu

Diana Munoz

Song Han

Manjunath Nimmakayalu

Peter C Hu

Jianli Dong

Affiliations

Soon will be listed here.

Abstract

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.

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