Clinicopathological significance of calreticulin in breast invasive ductal carcinoma

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 cance...

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Bibliographic Details
Published in:Modern pathology 2010-12, Vol.23 (12), p.1559-1566
Main Authors: Lwin, Zin-Mar, Guo, Chunhua, Salim, Agus, Yip, George Wai-Cheong, Chew, Fook-Tim, Nan, Jiang, Thike, Aye Aye, Tan, Puay-Hoon, Bay, Boon-Huat
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Biomarkers
Biomarkers, Tumor - analysis
Biomarkers, Tumor - metabolism
Blotting, Western
Breast cancer
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Calreticulin - analysis
Calreticulin - biosynthesis
Carcinoma, Ductal, Breast - metabolism
Carcinoma, Ductal, Breast - pathology
Cells
Endoplasmic reticulum
Epidemiology
Epidermal growth factor
Female
Fluorescent Antibody Technique
Hospitals
Humans
Immunohistochemistry
Metastasis
Middle Aged
Pathology
Prognosis
Proteins
Reverse Transcriptase Polymerase Chain Reaction
Tissue Array Analysis
Young Adult
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Summary: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.
ISSN:0893-3952
1530-0285
DOI:10.1038/modpathol.2010.173