The frequency and clinical significance of centromere enumeration probe 17 alterations in human epidermal growth factor receptor 2 immunohistochemistry-equivocal invasive breast cancer
Published Date: 25th July 2022
Publication Authors: Chagla LS
Background and Aims
Keratinocyte or non-melanoma skin cancer (NMSC) is the most common malignancy worldwide, encompassing basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). The mainstay of treatment for NMSC is excision. The likelihood of recurrence is directly related to achieving tumour-free margins. Just 1 per cent of BCCs recur where margins are clear1,2, compared with 31–41 per cent when margins are involved3,4. Equivalent data for cSCC are lacking but, given the metastatic potential (5–47 per cent)5, complete excision is paramount. In the UK, the majority of complex and high-risk skin cancers are excised by plastic surgeons.
Methods and Results
A large BC cohort (n = 6049) with HER2 immunohistochemistry score 2+ and florescent in-situ hybridisation (FISH) results was included to assess the prevalence of CEP17 alterations. Another cohort (n = 885) with available clinicopathological data was used to evaluate the effect of CEP17 in the setting of NAT. HER2-amplified tumours with monosomy 17 (CEP17 copy number < 1.5 per nucleus), normal 17 (CEP17 1.5–< 3.0) and polysomy 17 (CEP17 ≥ 3.0) were observed in 16, 59 and 25%, respectively, compared with 3, 74 and 23%, respectively, in HER2-non-amplified tumours. There was no significant relationship between CEP17 alterations and pathological complete response (pCR) rate in both HER2-amplified and HER2-non-amplified tumours. The independent predictors of pCR were oestrogen (ER) negativity in HER2-amplified tumours [ER negative versus positive; odds ratio (OR) = 11.80; 95% confidence interval (CI) = 1.37–102.00; P = 0.02], and histological grade 3 in HER2 non-amplified tumours (3 versus 1, 2; OR = 5.54; 95% CI = 1.61–19.00; P = 0.007).
Conclusion
The impacts of CEP17 alterations are not as strong as those of HER2/CEP17 ratio and HER2 copy number. The hormonal receptors status and tumour histological grade are more useful to identify BC patients with a HER2 immunohistochemistry-equivocal score who would benefit from NAT.
Katayama, A; Chagla, L et al. (2022). The frequency and clinical significance of centromere enumeration probe 17 alterations in human epidermal growth factor receptor 2 immunohistochemistry-equivocal invasive breast cancer. Histopathology. epub 25 Jul(.), p... [Online]. Available at: https://onlinelibrary.wiley.com/doi/full/10.1111/his.14728 [Accessed 15 August 2022]
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