ABSTRACT
We have recently characterized ITIH5 as a new extracellular matrix protein that exhibits clear expression loss in a variety of human tumour entities, including breast cancer. The aim of the present study was to decipher the molecular cause of ITIH5 expression loss in breast cancer and to learn more about the possible role of this molecule in cancer diseases. ITIH5 protein expression was found to be strongly reduced in 42% of invasive breast carcinomas-interestingly, with significant association with poor patient outcome. ITIH5 promoter methylation was frequently detected in breast cell lines and in primary carcinomas (40%), and it was functionally correlated with loss of ITIH5 mRNA expression. Moreover, ITIH5 promoter methylation was also significantly associated with poor clinical patient outcome and also with the occurrence of lymph node and distant metastases. In conclusion, we propose that ITIH5 may represent a novel metastasis repressor in human breast cancer. Both ITIH5 protein expression and ITIH5 promoter methylation may serve as prognostic biomarkers, thereby helping improve clinical patient outcome.
Subject(s)
Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Carcinoma, Ductal/genetics , Carcinoma, Intraductal, Noninfiltrating/genetics , DNA Methylation/genetics , Gene Silencing , Promoter Regions, Genetic/genetics , Proteinase Inhibitory Proteins, Secretory/genetics , Breast Neoplasms/pathology , Carcinoma, Ductal/pathology , Carcinoma, Intraductal, Noninfiltrating/pathology , Cell Line, Tumor , Disease Progression , Female , Follow-Up Studies , Gene Expression Regulation, Neoplastic/genetics , Humans , Neoplasm Invasiveness , Neoplasm Staging , Oligonucleotide Array Sequence Analysis , Phenotype , Prognosis , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
We report a case of multifocal urothelial carcinoma in situ of the left ureter with early stromal invasion and concomitant in situ lesions in bladder, prostate and seminal vesicle. After complete topographical mapping of the cystoprostatovesiculectomy specimen the unusual manifestation of urothelial carcinoma in situ in a seminal vesicle turned out to be a tumour spread via the ductus ejaculatorius into the seminal vesicle. DNA sequencing of the tumour suppressor gene TP53 of different tumour lesions revealed identical wild-type sequences.
