Association between the Expression of KISS1, KISS1R and MMP-9 in Invasive Breast Carcinomas

Abstract

Metastases are the leading cause of fatal outcome in patients with breast cancer, therefore different proteins related to metastasis are widely studied for the potential to control the spread of cancer cells. It has been shown in various types of cancers that the anti-metastatic role of the KISS1/KISS1R system has been performed by suppressing metalloproteinase 9 (MMP-9) expression, but there is evidence that the relationship between KISS1/KISS1R signalling and MMP-9 in breast cancer seems to be different. The aim of the current study was to assess the association between protein expression of KISS1, KISS1R and MMP-9 using software-based measurement of staining intensity and the possible link to tumour size, grade and receptor status in invasive breast carcinomas. Standard histopathological parameters were determined by an experienced pathologist and immunohistochemical staining for KISS1, KISS1R and MMP-9 was performed on tissue samples from 54 patients. Evaluation of staining intensity was performed using ImageJ software on RGB images by two operators. Results showed significant strong positive correlation between KISS1, KISS1R and MMP-9 and strong expression of studied proteins in tumour associated stromal cells. No association was found between the expression of the studied proteins and size, receptor status or grade. Higher expression of KISS1R, however, was observed in HER2-negative compared to HER2-positive carcinomas, which might indicate an alternative pathway for stimulating pro- proliferation of tumour cells when HER2 expression is low.