title: Prognostic value of matrix metalloproteinases (MMP-2 and MMP-9) in patients with lymph node-negative breast carcinoma.
abstract: Twenty-five to thirty percent of patients with node-negative breast cancer are expected to relapse following surgery, therefore great efforts have been made to identify new prognostic markers that could be useful in defining patients for additional therapy. The expression of MMP-2 and MMP-9 has been associated with high potential of metastasis in several human carcinomas including breast cancer. In the present study we examined the prognostic value of immunoreactive MMP-2/MMP-9 protein in 270 consecutive lymph node negative cases who received radical mastectomy or modified radical mastectomy. Among the patients, 211 cases received adjuvant endocrine therapy and/or adjuvant chemotherapy. Using immunohistochemical assay, we found that 56.7% of the resected tumors were positive for MMP-2 whereas 59.6% of the samples were positive for MMP-9. Chi2 test demonstrated a significant direct association between MMP-2 and MMP-9 (p < 0.001); positive immunostaining of MMP-2 was significantly related to higher tumor grade (p < 0.001) and larger tumor size (p = 0.012); positive immunostaining of MMP-9 was significantly related to higher tumor grade (p = 0.002). In univariate analysis, using Cox-proportional hazard model we found MMP-2, MMP-9 and the co-expression of MMPs (MMP2/MMP9) were significantly associated with patients' relapse free survival (p = 0.016, 0.015 and 0.013 respectively) but not overall survival (p = 0.122, 0.320 and 0.091 respectively). Log-rank test also showed that MMP-2, MMP-9 or the co-expression of MMP2/MMP9 was unfavorable prognostic factor for relapse free survival but not overall survival. In subgroup analysis, we found MMPs were more prognostic for patients with no adjuvant treatment than for patients with adjuvant therapy. In multivariate analysis, using Cox-proportional hazard model we found co-expression of MMPs, larger tumor size and higher tumor grade were unfavorable for relapse free survival (p = 0.038, 0.007 and 0.015 for each). We concluded that MMP-2 and MMP-2 are unfavorable prognostic factors in breast cancer patients. They might be potential predictive factor for adjuvant systemic therapy. The co-expression of MMP-2 and MMP-9 has significantly prognostic value in node-negative patients.
authors.affiliation: Department of Breast Surgery, Cancer Hospital/Cancer Institute, Fudan University, Shanghai, PR China.
authors.forename: He-Cheng
authors.initials: HC
authors.lastname: Li
authors.forename: Dao-Cheng
authors.initials: DC
authors.lastname: Cao
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Yi-Feng
authors.initials: YF
authors.lastname: Hou
authors.forename: Jiong
authors.initials: J
authors.lastname: Wu
authors.forename: Jin-Song
authors.initials: JS
authors.lastname: Lu
authors.forename: Gen-Hong
authors.initials: GH
authors.lastname: Di
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Fang-Ming
authors.initials: FM
authors.lastname: Li
authors.forename: Zhou-Luo
authors.initials: ZL
authors.lastname: Ou
authors.forename: Cui
authors.initials: C
authors.lastname: Jie
authors.forename: Zhen-Zhou
authors.initials: ZZ
authors.lastname: Shen
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Shao
mesh_terms: D018931:Antineoplastic Agents, Hormonal; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015411:Mastectomy, Modified Radical; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D018931:Antineoplastic Agents, Hormonal; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9