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High preoperative plasma TIMP‐1 is prognostic for early relapse in primary breast carcinoma
Author(s) -
Kuvaja Paula,
TalvensaariMattila Anne,
TurpeenniemiHujanen Taina
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23531
Subject(s) - medicine , quartile , proportional hazards model , oncology , breast carcinoma , univariate analysis , breast cancer , carcinoma , prospective cohort study , prognostic variable , survival analysis , multivariate analysis , cancer , gastroenterology , confidence interval
TIMP‐1 is a natural inhibitor of extracellular matrix degrading enzymes called matrix metalloproteinases. In addition to its capacity to inhibit matrix degradation, TIMP‐1 has been shown to promote cell growth and inhibit apoptosis. The expression of TIMP‐1 in tumor tissue, as well as in circulating blood, has therefore been shown to associate with worsened survival in several malignancies. In our study, a prospective series of 213 patients with primary breast carcinoma was assessed. Circulating pre‐ and postoperative TIMP‐1 levels were assayed using enzyme‐linked immunosorbent assay analysis. It was shown that high preoperative plasma TIMP‐1 was a powerful predictor of systemic early relapse in breast carcinoma, with HR 8.1 (95% CI 1.8–37.6) ( p = 0.007) as a log‐transformed continuous variable in Cox regression univariate analysis. It was shown to be independent of, and superior to, nodal status as a prognostic variable in multivariate analysis, and not associated with any known prognostic clinicopathological parameters. Kaplan‐Meier analysis showed that the patients belonging to the highest quartile of circulating TIMP‐1 levels had a worsened recurrence‐free survival of 79% compared to 94% RFS among patients in the lower quartiles ( p = 0.016). The postoperative levels of circulating plasma TIMP‐1 were not found to be prognostic for relapse. In conclusion, preoperative plasma TIMP‐1 was found to be a powerful prognostic factor for early systemic relapse in primary breast carcinoma. © 2008 Wiley‐Liss, Inc.