Moderate over-expression of HER2 may be cause of late recurrences of breast cancer.

B132 Over-expression of HER2 oncogene is generally caused by gene9s amplification. It leads to increasing gene copies number and consequently elevating transcription, translation levels that finally lead to high amount HER2 on the cell surface. This condition of cancer cell was described in details and it accompanies by high level of proliferation of cancer cells, inhibiting apoptosis bed survival and poor prognosis. But small proportion of breast cancer cases exist with over-expression of HER2, but without gene9s amplification. These cases are divided on two types. Over-expression in the first of them is caused by polysomia of 17 chromosome, so result of it is also increasing number of gene but with whole chromosome. Over-expression in the second type is caused by high ("non-stop") transcription of existing diploid number of 17 chromosome and so HER2 gene. Over-expression of HER2 without gene9s amplification is very poor investigated and even aren9t recognized by some authors. We have investigated 96 cases of breast cancer with positive immunohistochemical reaction of HER2. Expression of E-cadherin, Ki-67, progesterone and estrogen receptors were analyzed by immunohistochemistry. Expression of E-cadherin has been low in all cases. It points on increasing metastasis potential of such cancer cells. Generally breast cancer cases with over-expression of HER2 have shown relatively high level of proliferation (measured by Ki-67 expression) and absence of hormone receptors. But little amount of cases with over-expression of HER2 have shown low level of proliferation, preserved expression of estrogen receptors and disappearance of progesterone receptors. Such phenotype suggests good survival, latent development of tumor. But increasing potential for metastasis and inhibition of apoptosis suggest late recurrences. Recently we have analyzed some cases from last group via chromogenic in situ hybridization reaction (CISH). We have revealed polysomia of 17 chromosome in these cases. At present we proceeded clinical review for two cases and it was found that both cases are recurrences, moreover survival of these woman were 7 years for the first women and 12 years for the second . We have compared phenotypes of primary tumors and recurrences (which were available in our archive) and they are identical. It suggests that moderate over-expression of HER2, which is not accompanied by gene9s amplification may lead to latent behavior of tumor and late recurrences in future.