title: Calpastatin is associated with lymphovascular invasion in breast cancer.
abstract: Metastasis of breast cancer is a major contributor to mortality. Histological assessment of vascular invasion (VI) provides important prognostic information and demonstrates that VI occurs predominantly via lymphatics in breast cancer. We sought to examine genes and proteins involved in lymphovascular invasion (LVI) to understand the mechanisms of this key disease process. A gene expression array of 91 breast cancer patients was analysed by an Artificial Neural Network (ANN) approach using LVI to supervise the analysis. 89 transcripts were significantly associated (p<0.001) with the presence of LVI. Calpastatin, a specific calpain inhibitor, had the second lowest selection error and was investigated in breast cancer specimens using real-time PCR (n=56) and immunohistochemistry (n=53). Both calpastatin mRNA and protein levels were significantly associated with the presence of LVI (p=0.014 and p=0.025 respectively). The data supports the hypothesis that calpastatin may play a role in regulating the initial metastatic dissemination of breast cancer.
authors.affiliation: Academic Oncology, University of Nottingham, School of Molecular Medical Sciences, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham NG5 1PB, UK.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Storr
authors.forename: Rabab A A
authors.initials: RA
authors.lastname: Mohammed
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Woolston
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Green
authors.forename: Tim
authors.initials: T
authors.lastname: Parr
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Spiteri
authors.forename: Carlos
authors.initials: C
authors.lastname: Caldas
authors.forename: Graham R
authors.initials: GR
authors.lastname: Ball
authors.forename: Ian O
authors.initials: IO
authors.lastname: Ellis
authors.forename: Stewart G
authors.initials: SG
authors.lastname: Martin
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002154:Calpain / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011237:Predictive Value of Tests; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D002135:Calcium-Binding Proteins; C033668:calpastatin; D002154:Calpain