Tumor Microenvironment of Metastasis in Human Breast Carcinoma: A Potential Prognostic Marker Linked to Hematogenous Dissemination
Purpose: Multiphoton-based intravital imaging has shown that invasive carcinoma cells in mouse and rat mammary tumors intravasate when associated with perivascular macrophages, identifying a potential tumor microenvironment of metastasis (TMEM). We define TMEM as the tripartite arrangement of an inv...
| Main Authors: | , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
American Association for Cancer Research
2014
|
| Online Access: | http://hdl.handle.net/1721.1/84614 https://orcid.org/0000-0003-3214-4554 |
| _version_ | 1826189583826550784 |
|---|---|
| author | Gertler, Frank Robinson, Brian D. Sica, Gabriel L. Liu, Yi-Fang Rohan, Thomas E. Condeelis, John S. Jones, Joan G. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Gertler, Frank Robinson, Brian D. Sica, Gabriel L. Liu, Yi-Fang Rohan, Thomas E. Condeelis, John S. Jones, Joan G. |
| author_sort | Gertler, Frank |
| collection | MIT |
| description | Purpose: Multiphoton-based intravital imaging has shown that invasive carcinoma cells in mouse and rat mammary tumors intravasate when associated with perivascular macrophages, identifying a potential tumor microenvironment of metastasis (TMEM). We define TMEM as the tripartite arrangement of an invasive carcinoma cell, a macrophage, and an endothelial cell. The aim of this study was to determine if TMEM density in human breast carcinoma samples predicts the development of systemic, hematogenous metastases.
Experimental Design: A case-control study of 30 patients who developed metastatic breast cancer and 30 patients without metastatic disease was done. Cases were matched to controls based on currently used prognostic criteria. Paraffin-embedded primary breast cancer samples were stained using a triple immunohistochemical method allowing simultaneous identification of carcinoma cells, macrophages, and endothelial cells. Two pathologists, blinded to outcome, evaluated the number of TMEM per 20 high-power fields.
Results: No association was seen between TMEM density and tumor size or grade, lymph node metastasis, lymphovascular invasion, or hormone receptor status. TMEM density was greater in the group of patients who developed systemic metastases compared with the patients with only localized breast cancer (median, 105 versus 50, respectively; P = 0.00006). For every 10-unit increase in TMEM density, the odds ratio for systemic metastasis was 1.9 (95% confidence interval, 1.1-3.4).
Conclusions: TMEM density predicted the development of systemic, hematogenous metastases. The ability of TMEM to predict distant metastasis was independent of lymph node status and other currently used prognosticators. Quantitation of TMEM may be a useful new prognostic marker for breast cancer patients. |
| first_indexed | 2024-09-23T08:17:57Z |
| format | Article |
| id | mit-1721.1/84614 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:17:57Z |
| publishDate | 2014 |
| publisher | American Association for Cancer Research |
| record_format | dspace |
| spelling | mit-1721.1/846142022-09-30T08:50:47Z Tumor Microenvironment of Metastasis in Human Breast Carcinoma: A Potential Prognostic Marker Linked to Hematogenous Dissemination Gertler, Frank Robinson, Brian D. Sica, Gabriel L. Liu, Yi-Fang Rohan, Thomas E. Condeelis, John S. Jones, Joan G. Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Gertler, Frank Purpose: Multiphoton-based intravital imaging has shown that invasive carcinoma cells in mouse and rat mammary tumors intravasate when associated with perivascular macrophages, identifying a potential tumor microenvironment of metastasis (TMEM). We define TMEM as the tripartite arrangement of an invasive carcinoma cell, a macrophage, and an endothelial cell. The aim of this study was to determine if TMEM density in human breast carcinoma samples predicts the development of systemic, hematogenous metastases. Experimental Design: A case-control study of 30 patients who developed metastatic breast cancer and 30 patients without metastatic disease was done. Cases were matched to controls based on currently used prognostic criteria. Paraffin-embedded primary breast cancer samples were stained using a triple immunohistochemical method allowing simultaneous identification of carcinoma cells, macrophages, and endothelial cells. Two pathologists, blinded to outcome, evaluated the number of TMEM per 20 high-power fields. Results: No association was seen between TMEM density and tumor size or grade, lymph node metastasis, lymphovascular invasion, or hormone receptor status. TMEM density was greater in the group of patients who developed systemic metastases compared with the patients with only localized breast cancer (median, 105 versus 50, respectively; P = 0.00006). For every 10-unit increase in TMEM density, the odds ratio for systemic metastasis was 1.9 (95% confidence interval, 1.1-3.4). Conclusions: TMEM density predicted the development of systemic, hematogenous metastases. The ability of TMEM to predict distant metastasis was independent of lymph node status and other currently used prognosticators. Quantitation of TMEM may be a useful new prognostic marker for breast cancer patients. National Institutes of Health (U.S.) (Grant GM58801) National Cancer Institute (U.S.). Integrative Cancer Biology Program (Grant 1-U54-CA112967) 2014-01-31T16:02:43Z 2014-01-31T16:02:43Z 2009-03 2008-12 Article http://purl.org/eprint/type/JournalArticle 1078-0432 1557-3265 http://hdl.handle.net/1721.1/84614 Robinson, B. D., G. L. Sica, Y.-F. Liu, T. E. Rohan, F. B. Gertler, J. S. Condeelis, and J. G. Jones. “Tumor Microenvironment of Metastasis in Human Breast Carcinoma: A Potential Prognostic Marker Linked to Hematogenous Dissemination.” Clinical Cancer Research 15, no. 7 (March 10, 2009): 2433-2441. https://orcid.org/0000-0003-3214-4554 en_US http://dx.doi.org/10.1158/1078-0432.ccr-08-2179 Clinical Cancer Research Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf American Association for Cancer Research PMC |
| spellingShingle | Gertler, Frank Robinson, Brian D. Sica, Gabriel L. Liu, Yi-Fang Rohan, Thomas E. Condeelis, John S. Jones, Joan G. Tumor Microenvironment of Metastasis in Human Breast Carcinoma: A Potential Prognostic Marker Linked to Hematogenous Dissemination |
| title | Tumor Microenvironment of Metastasis in Human Breast Carcinoma: A Potential Prognostic Marker Linked to Hematogenous Dissemination |
| title_full | Tumor Microenvironment of Metastasis in Human Breast Carcinoma: A Potential Prognostic Marker Linked to Hematogenous Dissemination |
| title_fullStr | Tumor Microenvironment of Metastasis in Human Breast Carcinoma: A Potential Prognostic Marker Linked to Hematogenous Dissemination |
| title_full_unstemmed | Tumor Microenvironment of Metastasis in Human Breast Carcinoma: A Potential Prognostic Marker Linked to Hematogenous Dissemination |
| title_short | Tumor Microenvironment of Metastasis in Human Breast Carcinoma: A Potential Prognostic Marker Linked to Hematogenous Dissemination |
| title_sort | tumor microenvironment of metastasis in human breast carcinoma a potential prognostic marker linked to hematogenous dissemination |
| url | http://hdl.handle.net/1721.1/84614 https://orcid.org/0000-0003-3214-4554 |
| work_keys_str_mv | AT gertlerfrank tumormicroenvironmentofmetastasisinhumanbreastcarcinomaapotentialprognosticmarkerlinkedtohematogenousdissemination AT robinsonbriand tumormicroenvironmentofmetastasisinhumanbreastcarcinomaapotentialprognosticmarkerlinkedtohematogenousdissemination AT sicagabriell tumormicroenvironmentofmetastasisinhumanbreastcarcinomaapotentialprognosticmarkerlinkedtohematogenousdissemination AT liuyifang tumormicroenvironmentofmetastasisinhumanbreastcarcinomaapotentialprognosticmarkerlinkedtohematogenousdissemination AT rohanthomase tumormicroenvironmentofmetastasisinhumanbreastcarcinomaapotentialprognosticmarkerlinkedtohematogenousdissemination AT condeelisjohns tumormicroenvironmentofmetastasisinhumanbreastcarcinomaapotentialprognosticmarkerlinkedtohematogenousdissemination AT jonesjoang tumormicroenvironmentofmetastasisinhumanbreastcarcinomaapotentialprognosticmarkerlinkedtohematogenousdissemination |