Abstract
Introduction. It is essential to accurately identify HER2-amplified tumors for effective classification and treatment of breast cancer patients. The most precise method for detecting HER2 gene amplification is fluorescence in situ hybridization (FISH) testing. When tumor status is uncertain in IHC analysis, FISH testing becomes necessary for proper classification into the category of triple-positive carcinomas. Data on the biology of such tumors and their response to therapy are limited and inconsistent, which makes this topic an interesting area for further research.
Aim. To characterize the distribution of HER2 FISH testing results in ER+/PR+ breast cancer.
Materials and methods. 247 samples of ER+/PR+ breast tumors were studied. The HER2 gene amplification was analyzed using the fluorescence in situ hybridization (FISH) method. The average number of signals from the centromere of chromosome 17 (CEN17) and HER2 gene per nucleus, as well as their ratio, were calculated. The results were grouped according to the level of amplification.
Results. In the triple-positive carcinoma group, the distribution of amplification groups was as follows: group 1 (HER2/CEN17 signal ratio ≥ 2.0, HER2 signals/cell nucleus ≥ 4.0) — 91.7 %, group 3 (HER2/CEN17 signal ratio < 2.0, HER2 signals/cell nucleus ≥ 6.0) — 7.3 %, group 4 (HER2/CEN17 signal ratio < 2.0, HER2 signals/cell nucleus 4.0 - 6.0) — 0.91 %. "Non-classical" FISH results were found in 92.8 % of cases. In the ER+/PR+/HER2- carcinoma group, the frequency of "non-classical" results was 30.4 %.
Сonclusion. In the triple-positive breast cancer group, the frequency of "non-classical" FISH results is 9 times higher than the frequency of such results in the general testing cohort (according to literature data) and 2 times higher than the frequency of such results in the ER+/PR+/HER2- cancer group. These results may be due to bidirectional crosstalk between the estrogen receptors and HER2 signaling pathways and may determine the biology of this group of tumors. Limited data on the interpretation and clinical significance of "non-classical" FISH results make it difficult to choose drug therapy for patients with breast cancer and determine the prognosis of the disease.
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