Introduction: Genetic predisposition is one of the important risk factors that increase the incidence of breast cancer. The Her-2/neu gene is considered the most frequently amplified oncogene and is accompanied with either amplification or deletion of the TOP2A gene with an equal frequency.
Aim of the study: The aim of the study was to compare patients with familial breast cancer (FBC) with those having sporadic breast cancer (SBC) and also to evaluate the combined study on the hormonal status, immunostaining for Her-2/neu, and Her-2/neu and TOP2A copy number alterations by fluorescence in-situ hybridization (FISH).
Patients and methods: A total of 22 patients with invasive breast carcinomas were involved: 12 positive for the criteria that define FBC and 10 positive for SBC. Representative sections of formalin-fixed paraffin-embedded blocks were subjected to immunostaining for Her-2/neu (Hercep test), estrogen receptors, and progesterone receptors and also to FISH in order to evaluate TOP2A and Her-2/neu copy number alterations.
Results: FBC tumors were more aggressive than SBC tumors, as assessed by pathological parameters and immunohistochemical markers (lower estrogen receptor and progesterone receptor expression). However, the frequency of Her-2/neu gene amplification and protein overexpression was equal between the two groups. TOP2A gene amplification was observed in 25% of FBC patients compared with 20% of SBC patients. Coamplification of both Her-2/neu and TOP2A genes was observed in 8.3% of FBC patients and in 20% of SBC patients. In contrast, Her-2/neu amplification alone was observed in 25% of FBC patients compared with 10% of SBC patients. Importantly, TOP2A amplification without Her-2/neu gene amplification was observed in 16.7% of FBC patients but was not observed among SBC patients.
Conclusion: FBC tumors were more aggressive than SBC tumors. This study suggests that TOP2A gene amplification occurs both in FBC and in SBC patients but more frequently among FBC patients. Moreover, TOP2A gene amplification may occur independent of Her-2/neu amplification. We can conclude that this parameter should be determined on a routine basis in breast cancer patients, especially when FBC is suspected. In addition, a combined approach using immunohistochemical analysis and FISH can optimize Her-2/neu testing for breast carcinoma patients, especially among those with immunohistochemistry-equivocal tumors.