Stromal ColXα1 expression correlates with tumor-infiltrating lymphocytes and predicts adjuvant therapy outcome in ER-positive/HER2-positive breast cancer
Abstract Background The breast cancer microenvironment contributes to tumor progression and response to chemotherapy. Previously, we reported that increased stromal Type X collagen α1 (ColXα1) and low TILs correlated with poor pathologic response to neoadjuvant therapy in estrogen receptor and HER2-...
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| Format: | Article |
| Language: | English |
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BMC
2019-11-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12885-019-6134-y |
| _version_ | 1818157771675140096 |
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| author | Chaohui Lisa Zhao Kamaljeet Singh Alexander S. Brodsky Shaolei Lu Theresa A. Graves Mary Anne Fenton Dongfang Yang Ashlee Sturtevant Murray B. Resnick Yihong Wang |
| author_facet | Chaohui Lisa Zhao Kamaljeet Singh Alexander S. Brodsky Shaolei Lu Theresa A. Graves Mary Anne Fenton Dongfang Yang Ashlee Sturtevant Murray B. Resnick Yihong Wang |
| author_sort | Chaohui Lisa Zhao |
| collection | DOAJ |
| description | Abstract Background The breast cancer microenvironment contributes to tumor progression and response to chemotherapy. Previously, we reported that increased stromal Type X collagen α1 (ColXα1) and low TILs correlated with poor pathologic response to neoadjuvant therapy in estrogen receptor and HER2-positive (ER+/HER2+) breast cancer. Here, we investigate the relationship of ColXα1 and long-term outcome of ER+/HER2+ breast cancer patients in an adjuvant setting. Methods A total of 164 cases with at least 5-year follow-up were included. Immunohistochemistry for ColXα1 was performed on whole tumor sections. Associations between ColXα1expression, clinical pathological features, and outcomes were analyzed. Results ColXα1 expression was directly proportional to the amount of tumor associated stroma (p = 0.024) and inversely proportional to TILs. Increased ColXα1 was significantly associated with shorter disease free survival and overall survival by univariate analysis. In multivariate analysis, OS was lower in ColXα1 expressing (HR = 2.1; 95% CI = 1.2–3.9) tumors of older patients (> = 58 years) (HR = 5.3; 95% CI = 1.7–17) with higher stage (HR = 2.6; 95% CI = 1.3–5.2). Similarly, DFS was lower in ColXα1 expressing (HR = 1.8; 95% CI = 1.6–5.7) tumors of older patients (HR = 3.2; 95% CI = 1.3–7.8) with higher stage (HR = 2.7; 95% CI = 1.6–5.7) and low TILs. In low PR+ tumors, higher ColXα1 expression was associated with poorer prognosis. Conclusion ColXα1 expression is associated with poor disease free survival and overall survival in ER+/HER2+ breast cancer. This study provides further support for the prognostic utility of ColXα1 as a breast cancer associated stromal factor that predicts response to chemotherapy. |
| first_indexed | 2024-12-11T15:19:30Z |
| format | Article |
| id | doaj.art-f91ad71a403846a2922564339a7eac6e |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-11T15:19:30Z |
| publishDate | 2019-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-f91ad71a403846a2922564339a7eac6e2022-12-22T01:00:26ZengBMCBMC Cancer1471-24072019-11-011911810.1186/s12885-019-6134-yStromal ColXα1 expression correlates with tumor-infiltrating lymphocytes and predicts adjuvant therapy outcome in ER-positive/HER2-positive breast cancerChaohui Lisa Zhao0Kamaljeet Singh1Alexander S. Brodsky2Shaolei Lu3Theresa A. Graves4Mary Anne Fenton5Dongfang Yang6Ashlee Sturtevant7Murray B. Resnick8Yihong Wang9Department of Pathology and Laboratory Medicine, Rhode Island Hospital and Lifespan Medical Center, Warren Alpert Medical School of Brown UniversityDepartment of Pathology and Laboratory Medicine, Women and Infant Hospital, Warren Alpert Medical School of Brown UniversityDepartment of Pathology and Laboratory Medicine, Rhode Island Hospital and Lifespan Medical Center, Warren Alpert Medical School of Brown UniversityDepartment of Pathology and Laboratory Medicine, Rhode Island Hospital and Lifespan Medical Center, Warren Alpert Medical School of Brown UniversityDepartment of Surgery, Rhode Island Hospital and Lifespan Medical Center, Warren Alpert Medical School of Brown UniversityDepartment of Medicine, Rhode Island Hospital and Lifespan Medical Center, Warren Alpert Medical School of Brown UniversityDepartment of Pathology and Laboratory Medicine, Rhode Island Hospital and Lifespan Medical Center, Warren Alpert Medical School of Brown UniversityDepartment of Pathology and Laboratory Medicine, Rhode Island Hospital and Lifespan Medical Center, Warren Alpert Medical School of Brown UniversityDepartment of Pathology and Laboratory Medicine, Rhode Island Hospital and Lifespan Medical Center, Warren Alpert Medical School of Brown UniversityDepartment of Pathology and Laboratory Medicine, Rhode Island Hospital and Lifespan Medical Center, Warren Alpert Medical School of Brown UniversityAbstract Background The breast cancer microenvironment contributes to tumor progression and response to chemotherapy. Previously, we reported that increased stromal Type X collagen α1 (ColXα1) and low TILs correlated with poor pathologic response to neoadjuvant therapy in estrogen receptor and HER2-positive (ER+/HER2+) breast cancer. Here, we investigate the relationship of ColXα1 and long-term outcome of ER+/HER2+ breast cancer patients in an adjuvant setting. Methods A total of 164 cases with at least 5-year follow-up were included. Immunohistochemistry for ColXα1 was performed on whole tumor sections. Associations between ColXα1expression, clinical pathological features, and outcomes were analyzed. Results ColXα1 expression was directly proportional to the amount of tumor associated stroma (p = 0.024) and inversely proportional to TILs. Increased ColXα1 was significantly associated with shorter disease free survival and overall survival by univariate analysis. In multivariate analysis, OS was lower in ColXα1 expressing (HR = 2.1; 95% CI = 1.2–3.9) tumors of older patients (> = 58 years) (HR = 5.3; 95% CI = 1.7–17) with higher stage (HR = 2.6; 95% CI = 1.3–5.2). Similarly, DFS was lower in ColXα1 expressing (HR = 1.8; 95% CI = 1.6–5.7) tumors of older patients (HR = 3.2; 95% CI = 1.3–7.8) with higher stage (HR = 2.7; 95% CI = 1.6–5.7) and low TILs. In low PR+ tumors, higher ColXα1 expression was associated with poorer prognosis. Conclusion ColXα1 expression is associated with poor disease free survival and overall survival in ER+/HER2+ breast cancer. This study provides further support for the prognostic utility of ColXα1 as a breast cancer associated stromal factor that predicts response to chemotherapy.http://link.springer.com/article/10.1186/s12885-019-6134-yCollagenTumor infiltrating lymphocytesTumor microenvironmentBreast cancerAdjuvant chemotherapy |
| spellingShingle | Chaohui Lisa Zhao Kamaljeet Singh Alexander S. Brodsky Shaolei Lu Theresa A. Graves Mary Anne Fenton Dongfang Yang Ashlee Sturtevant Murray B. Resnick Yihong Wang Stromal ColXα1 expression correlates with tumor-infiltrating lymphocytes and predicts adjuvant therapy outcome in ER-positive/HER2-positive breast cancer BMC Cancer Collagen Tumor infiltrating lymphocytes Tumor microenvironment Breast cancer Adjuvant chemotherapy |
| title | Stromal ColXα1 expression correlates with tumor-infiltrating lymphocytes and predicts adjuvant therapy outcome in ER-positive/HER2-positive breast cancer |
| title_full | Stromal ColXα1 expression correlates with tumor-infiltrating lymphocytes and predicts adjuvant therapy outcome in ER-positive/HER2-positive breast cancer |
| title_fullStr | Stromal ColXα1 expression correlates with tumor-infiltrating lymphocytes and predicts adjuvant therapy outcome in ER-positive/HER2-positive breast cancer |
| title_full_unstemmed | Stromal ColXα1 expression correlates with tumor-infiltrating lymphocytes and predicts adjuvant therapy outcome in ER-positive/HER2-positive breast cancer |
| title_short | Stromal ColXα1 expression correlates with tumor-infiltrating lymphocytes and predicts adjuvant therapy outcome in ER-positive/HER2-positive breast cancer |
| title_sort | stromal colxα1 expression correlates with tumor infiltrating lymphocytes and predicts adjuvant therapy outcome in er positive her2 positive breast cancer |
| topic | Collagen Tumor infiltrating lymphocytes Tumor microenvironment Breast cancer Adjuvant chemotherapy |
| url | http://link.springer.com/article/10.1186/s12885-019-6134-y |
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