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PREVALENCE OF HER2 FLUORESCENCE IN SITU HYBRIDIZATION (FISH) POSITIVITY AND NEGATIVITY AMONG HER2 IMMUNOHISTOCHEMICAL STAIN EQUIVOCAL (2+) BREAST SPECIMENS: A CROSS SECTIONAL STUDY.

Author

Ian Fidel Aristotle R. Galapon

Related Institution

Department of Pathology - Baguio General Hospital and Medical Center - Department of Health

Publication Information

Publication Type
Research Report
Date
January 1, 2018-December 31, 2019

Abstract

Introduction: Breast cancer being the most common malignancy and a major cause of death among women, are diagnosed based on histopathologic examination. It has been a practice to use breast panel immunohistochemistry (ER, PR and HER-2) for prognostication and to direct patient treatment. The interpretation of HER-2, however, remains subjective. In line with this, a number of equivocal interpretation on immunohistochemistry (IHC) accounts for 15% of all breast cancer patients. These tumors with equivocal results require further testing through fluorescence in-situ hybridization (FISH) to confirm the expression of the HER-2 gene, making a patient eligible for trastuzumab therapy. FISH, however, is unavailable in the current setting, and specimens need to be transported to a FISH testing facility which is only available in the National Capital Region, not to mention the imposed restrictions in mobility and risk of exposure due to the COVID-19 pandemic. This study aimed to determine the prevalence of FISH HER-2 positivity and negativity among HER-2 IHC equivocal tumors of either core needle, excision biopsy and modified radical mastectomy specimens. Additionally, it aimed to determine correlation between FISH HER-2 status and each of the identified clinicopathologic characteristics (age, tumor type, tumor size and hormone receptor [ER/PR] status). Methodology: This is a cross-sectional study which made use of secondary data collection. A total of 60 cases (core needle [33], excision biopsy [1] and modified radical mastectomy [26]) with HER-2 equivocal results on IHC were selected using simple random sampling. The variables identified were age, tumor size, tumor type, hormone receptor status and FISH HER-2 status, and were evaluated using frequencies and percentages. Correlation between FISH HER-2 and each of the identified clinicopathologic characteristics were evaluated using chi-square. Results: Majority of cases with HER-2 equivocal IHC results were older than 50 years old (63.3%), have tumors of ductal type (70%), and have tumors greater than 2 cm but less than or equal to 5 cm (30%); though most cases submitted for FISH testing were core needle biopsies, so actual size was not measured. Hormone receptor positive cases comprise 86.7% and 81.7% of ER-positive and PR-positive, respectively. Only 16.7% of these IHC HER-2 equivocal cases expressed the HER-2 gene by FISH. The remaining 83.3% were negative for the HER-2 gene. Lastly, no significant relationship between FISH HER-2 status and clinicopathologic characteristics, was found. Conclusion: Even a skilled pathologist would encounter problems in interpreting immunohistochemistry. HER-2 interpretation, in particular, is largely subjective and it is almost inevitable that equivocal interpretation would suffice at times. More advanced methods exist to determine the expression of the gene. Fluorescence in-situ hybridization is of great utility to resolve the problem of subjective interpretation of IHC, guiding clinicians in prognostication and determining suitable treatment. Despite its cost, FISH provides certainty in providing proper management to further improve a patient's quality of life.

References

1. Amedos, M , Nerukar, A , Osin, P . Discordance between core needle biopsy and excisional biopsy for estrogen receptor, progesterone receptor and HER2 status in early breast cancer.Annals of Oncology 20(12): 2009
2. Agesborg, S , Mixon, C , Nguyen, T . Immunohistochemistry and alternative FISH testing in breast cancer with HER2 equivocal amplificationBreast Cancer Research and Treatment 170, 321-328, 2018
3. Zhang, H , Ren, G , Wang, X . HER-2 gene amplification by fluorescence in situ hybridization (FISH) compared with immunohistochemistry (IHC) in breast cancer: a study of 528 casesSpringerPlus 134, 743-749, 2012

Physical Location

LocationLocation CodeAvailable FormatAvailability
Baguio General Hospital 2600 Abstract Print Format

 
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