Investigating the impact of polysomy 17 in breast cancer patients with HER2 amplification through meta-analysis

Objectives Since studies regarding the effect of polysomy 17 (P17) in breast cancer cases with some specific clinical findings are few in number and are in small sample sizes, meta-analysis was implemented to exhibit the effects of P17 in patients with Human Epidermal growth factor Receptor 2 (HER2) amplification on lymph node involvement and tumor grade. Materials and methods Pubmed literature database was scanned up to June 2017 by using the keywords “polysomy 17 breast cancer” and 141 studies were accessed. Ultimately four of the reviewed papers have been found to be appropriate for examining the effect of P17 on lymph node involvement and tumor grade. Prior to meta-analysis, publication bias and heterogeneity of the studies was examined. Results Meta-analysis in the examining the effect of polysomy 17 on lymph node involvement (OR=1.708, 95% CI: 1.068–2.733), on grade [3]/[3,1] (OR=3.402, 95% CI: 1.726–6.707), on grade [3]/[3, 2] (OR=2.581, 95% CI: 0.778–8.559) and on grade [2]/[2,1] (OR=1.854, 95% CI: 0.531–6.468) was determined in those with HER2 amplification. Conclusion It was observed that in terms of lymph node involvement, P17 was a risk factor in patients and with regard to tumor grade, P17 was a risk factor when grade increased in patients with amplification.

Outcome of HER2 Testing by FISH applying ASCO/CAP 2007 and 2013 guideline in IHC equivocal group of breast cancer: Experience at tertiary cancer care centre

Background and Objectives: HER2 testing guideline of ASCO/CAP for interpretation and reporting has recently been revised. The study is aimed to measure the impact of 2013 CAP guideline on equivocal HER2 test outcome (immunohistochemistry [IHC] 2+) when tested by fluorescent in situ hybridization (FISH). The study also aims at finding the frequency of polysomy and monosomy of chromosome 17. Materials and Methods: Specimens were collected in Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India. IHC was performed in every case, and FISH was performed in IHC2+ cases. Results: In final analysis includes 557 subjects on the basis of CAP guideline 2007 and CAP guideline 2013. One hundred ninety-two subjects (34.4%) were HER2 amplified according to CAP scoring 2007, and 246 subjects (44%) according to 2013 CAP scoring. Conclusions: FISH results were evaluated (IHC2 + interpreted according to CAP 2007 guideline) with both 2007 and 2013 ASCO/CAP scoring criteria, we identified significantly more HER2 positive cases as compared to cases evaluated using the 2007 criteria (P < 0.05). We also found that in breast carcinoma, HER2 status in the presence of polysomy 17 may vary with the scoring criteria used. Evaluation of FISH result using 2013 ASCO/CAP criteria means that more patients with breast cancer may be appropriate for targeted treatment with trastuzumab, potentially improving their outcome.

Chromosome 17 polysomy: correlation with histological parameters and HER2NEU gene amplification

AimsHER2NEU gene amplification is present in the majority of invasive breast carcinomas that have HER2 protein overexpression. A subset of breast cancers harbour an increased chromosome 17 (CEP17) copy number (polysomy 17). We investigated the clinicopathologic significance of polysomy 17 in correlation with various histological parameters and HER2NEU gene amplification.MethodsWe collected the surgical specimens of 266 consecutive cases of primary invasive breast carcinomas. HER2NEU gene status and CEP17 copy numbers were assessed by fluorescent in situ hybridisation (FISH). Chromosome 17 polysomy was determined by the presence of ≥3 average CEP17 signals per nucleus.Results63 tumours (23.7%) harboured polysomy 17. Carcinomas with polysomy 17 were associated with adverse histological indicators including high histological grade, high nuclear grade, poor Nottingham Prognostic Index, advanced local tumour extent and progesterone receptor negativity. Polysomy 17 was common to HER2NEU amplified and unamplified tumours, and more frequently observed in HER2NEU unamplified (71.4%) cases.Conclusions In the absence of the gene amplification, HER2 protein overexpression may be explained by other mechanisms including polysomy 17.