FISH and HER2/ neu equivocal immunohistochemistry in breast carcinoma

Indian J Cancer. 2019 Apr-Jun;56(2):119-123. doi: 10.4103/ijc.IJC_333_18.

Abstract

Aim: The aim of this study was to validate the role of fluorescence in situ hybridization (FISH) in investigating HER2/neu gene amplification (human epidermal growth factor receptor 2) in patients with HER2/neu equivocal breast cancer diagnosed on immunohistochemistry (IHC).

Materials and methods: This was a retrospective study conducted from January 2013 to October 2017. A total of 134 patients diagnosed with invasive breast carcinoma and HER2/neu equivocal status on IHC were analyzed. Also, the cases for the years 2016 and 2017 formed a subgroup that was analyzed further to study the impact of pre-analytical factors on IHC and FISH results.

Results: A total of 134 women with HER2/neu IHC equivocal breast cancer were included in the study with a median age of 50 years (range 25-81). HER2/neu amplification by FISH was noted in 72 (54%) cases, whereas it was non-amplified in 52 (39%) cases. Ten cases were reported as equivocal even on FISH (ASCO/CAP 2013 guidelines). Polysomy 17 was noted in 55 cases (41%), of which 26 patients were≤50 years and 29 patients were >50 years of age. Twenty (36%) of these 55 cases showed HER2/neu amplification, whereas 26 (48%) cases were non-amplified and 9 (16%) cases were reported as equivocal on FISH. Also, more than half of the polysomy cases were hormone receptor negative.

Conclusion: IHC is a good screening tool for negative and positive results. Any patient targeted for trastuzumab therapy should undergo confirmation of HER2/neu equivocal status by FISH analysis. We also suggest that if a non-classical FISH pattern is seen, the test should be repeated with a non-centromeric chromosome 17 reference locus probe for better treatment planning.

Keywords: Breast carcinoma; FISH; HER2/neu; immunohistochemistry.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Chromosome Aberrations
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence*
  • Middle Aged
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / isolation & purification*
  • Retrospective Studies
  • Trastuzumab / therapeutic use

Substances

  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab