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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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| Published in: | Modern pathology 2010-12, Vol.23 (12), p.1559-1566 |
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| creator | 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 |
| description | 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. |
| doi_str_mv | 10.1038/modpathol.2010.173 |
| format | article |
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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.</description><identifier>ISSN: 0893-3952</identifier><identifier>EISSN: 1530-0285</identifier><identifier>DOI: 10.1038/modpathol.2010.173</identifier><identifier>PMID: 20834237</identifier><identifier>CODEN: MODPEO</identifier><language>eng</language><publisher>United States: Elsevier Limited</publisher><subject>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</subject><ispartof>Modern pathology, 2010-12, Vol.23 (12), p.1559-1566</ispartof><rights>Copyright Nature Publishing Group Dec 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-b26e6ca3b2113aafca5713b72ad0cd076796a15ba511858cdb36579dac71bd53</citedby><cites>FETCH-LOGICAL-c470t-b26e6ca3b2113aafca5713b72ad0cd076796a15ba511858cdb36579dac71bd53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,2744,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20834237$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lwin, Zin-Mar</creatorcontrib><creatorcontrib>Guo, Chunhua</creatorcontrib><creatorcontrib>Salim, Agus</creatorcontrib><creatorcontrib>Yip, George Wai-Cheong</creatorcontrib><creatorcontrib>Chew, Fook-Tim</creatorcontrib><creatorcontrib>Nan, Jiang</creatorcontrib><creatorcontrib>Thike, Aye Aye</creatorcontrib><creatorcontrib>Tan, Puay-Hoon</creatorcontrib><creatorcontrib>Bay, Boon-Huat</creatorcontrib><title>Clinicopathological significance of calreticulin in breast invasive ductal carcinoma</title><title>Modern pathology</title><addtitle>Mod Pathol</addtitle><description>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. 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Academic</collection><jtitle>Modern pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lwin, Zin-Mar</au><au>Guo, Chunhua</au><au>Salim, Agus</au><au>Yip, George Wai-Cheong</au><au>Chew, Fook-Tim</au><au>Nan, Jiang</au><au>Thike, Aye Aye</au><au>Tan, Puay-Hoon</au><au>Bay, Boon-Huat</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinicopathological significance of calreticulin in breast invasive ductal carcinoma</atitle><jtitle>Modern pathology</jtitle><addtitle>Mod Pathol</addtitle><date>2010-12</date><risdate>2010</risdate><volume>23</volume><issue>12</issue><spage>1559</spage><epage>1566</epage><pages>1559-1566</pages><issn>0893-3952</issn><eissn>1530-0285</eissn><coden>MODPEO</coden><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><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.</abstract><cop>United States</cop><pub>Elsevier Limited</pub><pmid>20834237</pmid><doi>10.1038/modpathol.2010.173</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| 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 |
| title | Clinicopathological significance of calreticulin in breast invasive ductal carcinoma |
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