An analysis of HER-2/neu gene status in invasive ductal carcinomas using immunohistochemistry and fluorescence in situ hybridization

Authors: REŞİT DOĞAN KÖSEOĞLU, AHMET MÜSLEHİDDİNOĞLU, ÜNAL ERKORKMAZ, JÜLİDE SALİHA CAFERLER, PERVİN DÜRER, YAVUZ HAKAN ÖZÖN

Abstract: To determine the concordance rates between results from immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assays for the HER-2/neu gene in cases of invasive ductal carcinoma. IHC and FISH are 2 of the most frequently used methods to determine HER-2/neu gene status in invasive breast carcinomas. Materials and methods: The present study includes 59 female patients with invasive ductal carcinoma. The mean age was 57.8 years. Axillary lymph node status could be evaluated in 30 patients with axillary dissection. HER-2/neu gene overexpression and amplification were analyzed in primary tumor tissues by IHC and FISH assays, respectively. The evaluation of the IHC assay was performed using a score of 0, 1+, 2+, or 3+, while a HER-2/neu-to-CEP17 ratio greater than 2 was accepted as positive for HER-2/neu gene amplification. Results: The overall rate of HER-2/neu gene amplification was 28.8% (17 cases) among all members of the study group, while this rate was 48% (12 cases) in the group with axillary lymph node metastasis. The rate of HER-2/neu overexpression (score of 3+) was 11.9% (7 cases). HER-2/neu gene amplification was associated with tumor grade (P < 0.05). There was a significant relationship between the results of the IHC and FISH assays (P < 0.001). All of the cases with a score of 3+ were FISH-positive, while 97% of cases with a score of 0 and 44% of cases with a score of 1+ were FISH-negative. HER-2/neu gene amplification was determined in 80% of the cases with a score of 2+. Among cases with positive lymph node status, the concordance rates were 100% in cases with scores of 0, 2+, and 3+, while this rate was found to be 29% in cases with a score of 1+. Conclusion: Our found rate (11.9%) of HER-2/neu overexpression was lower than the rates reported in the literature, while our HER-2/neu gene amplification rate (28.8%) was compatible with the reported rates. HER-2/neu gene amplification was associated with tumor grade. Although high rates of concordance between HER-2/neu gene overexpression and amplification in cases with scores of 2+ and 3+ were obtained, the discordance rate in cases with a score of 1+ was higher than those of other studies. The discordance rate in cases with a score of 1+ and positive lymph node status was higher than that of the total study group. According to our results, a score of 1+ indicated less conclusive immunostaining for the HER-2/neu gene, and cases with scores of 1+ in the metastatic group had a higher rate of HER-2/neu gene amplification than that of the total study group. Our results show that FISH analysis for HER-2/neu gene status should be performed in cases with an immunostaining score of 1+, especially in those cases with positive axillary lymph node results.

Keywords: Invasive breast carcinoma, HER-2/neu, FISH, IHC

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