Charakterisierung der putativen Klasse II Tumorsuppressorgene ITIH5, IRX1 und SCN4B im duktalen in situ Karzinom der Brust und ihre potentielle Eignung als Biomarker zur Risikoabschätzung

RWTH Publications (RWTH Aachen)

Abstract

Breast cancer is the most common tumour disease in women worldwide. Due to the mammography screening programme introduced at the beginning of the 2000s, the proportion of ductal carcinoma in situ (DCIS) has increased enormously and continues to rise due to increasingly sensitive screening methods. DCIS are a non-invasive precursor of ductal invasive carcinomas, but they are treated clinically as invasive tumours, as there are still no valid biomarkers. The aim of this work was to characterise the class II tumour suppressor gene (C2TSG) ITIH5 and the putative C2TSGs IRX1 and SCN4B in DCIS. In addition, the potential suitability of these three genes as tumour markers for DCIS and as markers for assessing the risk of malignant degeneration of DCIS into invasive ductal carcinoma was discussed. The tumour-suppressive role of the ITIH5 gene in particular has already been well studied in breast cancer. The IRX1 and SCN4B genes have already been investigated in other tumour entities, but have so far been little researched in breast cancer. A collective of paraffin-fixed tissue with DCIS tissue and normal breast tissue was compiled. The protein expression of the candidate genes was analysed using immunohistochemical staining. In addition, a promoter DNA methylation analysis was performed for ITIH5 using pyrosequencing. The data obtained were evaluated together with clinical and histological data. The promoter region of ITIH5 is hypermethylated in DCIS compared to normal tissue. This results in reduced ITIH5 protein expression in DCIS. IRX1 protein expression is also reduced in DCIS compared to normal tissue. There is no difference in SCN4B protein expression between normal tissue and DCIS. However, SCN4B protein expression shows a positive correlation with the expression of the hormone receptors estrogen receptor and progesterone receptor, whereas IRX1 protein expression correlates negatively with estrogen receptor expression. In summary, this study shows that there is no clear evidence for the suitability of all three genes as biomarkers in DCIS. Follow-up data must be collected for further investigation.

Authors 1

1. Cosima Maria Kunze corresponding Aachen

   RWTH Aachen University

   Affiliation as printed

   RWTH Aachen