Comparison of Immunohistochemical 2 (+) HER2 Gene Status with SISH in Invasive Breast Carcinoma

Background: The aim of this study is to evaluate the HER2 (c-erbB-2) gene status in patients with invasive breast cancer who have received an equivocal (2+) score during immunohistochemical (IHC) testing. The study employs the Silver DNA in Situ Hybridization (SISH) technique for this estimation and further investigates its association with various clinicopathological variables. Materials and methods: This study is a retrospective analysis consisting of 133 formalin-fixed paraffin-embedded tissue blocks from female patients diagnosed with invasive breast carcinoma and having an equivocal (2+) HER2 IHC score. HER2 DNA amplification in all cases was studied using the SISH technique. ER, PR, and Ki-67 stainings were evaluated by the IHC method. Results: From a total of 442 invasive breast carcinoma cases, 224 (50.70%) were found to be HER2 negative, 85 (19.20%) were HER2 3(+), and 133 (30.10%) had an equivocal 2+ HER2 score as determined by IHC. Among these 133 cases, HER-2 gene amplification was confirmed in 29.30% (39/133) by SISH. A statistically significant association was found between SISH status and Ki-67 index (P=0.04). Additionally, for cases with negative SISH results, a positive correlation was observed between the estrogen receptor (ER) and progesterone receptor (PR) statuses (P <0.01). Conclusion: The study underscores the importance of employing genetic tests like SISH to confirm the HER-2 gene status in cases with an equivocal 2+ IHC score. The SISH technique is emphasized as easy, time-efficient, cost-effective, and a reliable method for such confirmatory tests.