title: Clinicopathological significance of calreticulin in breast invasive ductal carcinoma.
abstract: Calreticulin is a chaperone protein located in the lumen of the endoplasmic reticulum. The association of calreticulin with pathological conditions such as autoimmune disorders and certain types of cancer have been reported. However, little is known about its role in the pathogenesis of breast cancer. The aim of this study was to determine the expression of calreticulin in vitro and correlate its expression levels in breast cancer tissue samples with clinicopathological parameters. Calreticulin expression was evaluated in MCF-7 and MDA-MB-231 breast cancer cells by real-time RT-PCR, Western blot, immunohistochemistry, and immunofluorescence staining. Patient tissue microarrays were constructed from 228 breast cancer specimens for immunohistochemical analysis. The in vitro study showed a higher calreticulin expression in more aggressive MDA-MB-231 cells as compared with MCF-7 cells at both mRNA and protein levels. In all, 227 out of 228 breast cancer samples exhibited calreticulin staining in at least 5% of the cancer cells. Calreticulin immunostaining was observed to be localized to the cytoplasm of the cancer cells. Regression analysis of calreticulin immunostaining in the tissue microarrays revealed that its expression was positively correlated to logarithm of (log) tumor size (P=0.046) and development of distant metastasis (P=0.017). Multivariate analysis confirmed calreticulin expression as an independent predictor of log tumor size and occurrence of distant metastasis. The data suggest that calreticulin expression is associated with more advanced tumors and is a potential prognostic biomarker.
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Zin-Mar
authors.initials: ZM
authors.lastname: Lwin
authors.forename: Chunhua
authors.initials: C
authors.lastname: Guo
authors.forename: Agus
authors.initials: A
authors.lastname: Salim
authors.forename: George Wai-Cheong
authors.initials: GW
authors.lastname: Yip
authors.forename: Fook-Tim
authors.initials: FT
authors.lastname: Chew
authors.forename: Jiang
authors.initials: J
authors.lastname: Nan
authors.forename: Aye Aye
authors.initials: AA
authors.lastname: Thike
authors.forename: Puay-Hoon
authors.initials: PH
authors.lastname: Tan
authors.forename: Boon-Huat
authors.initials: BH
authors.lastname: Bay
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D037282:Calreticulin / Q000032:analysis / Q000096:biosynthesis*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D037282:Calreticulin