The levels of tissue inhibitor of metalloproteinases 1 in plasma and tumor response to preoperative radiochemotherapy and survival in patients with rectal cancer
Background: The aim of this study was to analyze whether the level of tissue inhibitor of metalloproteinases (TIMP) 1 is associated with the tumor response and survival to preoperative radiochemotherapy in rectal cancer patients.
Patients and methods: Ninety-two patients with histologically confirmed non-metastatic rectal cancer of clinical stage I- III were treated with preoperative radiochemotherapy, surgery and postoperative chemotherapy. Plasma TIMP-1 concentrations were measured prior to the start of the treatment with an enzyme-linked immunosorbent assay (ELISA).
Results: Median follow-up time was 68 months (range: 3-93 months) and was 80 months (range: 68-93 months) in survivors. The 5-year locoregional control (LRC), disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) rates for all patients were 80.2%, 56.4%, 63.7% and 52.2%, respectively. The median TIMP-1 level was 185 ng/mL (range: 22-523 ng/mL) and the mean level (±standard deviation) was 192 (±87) ng/mL. Serum TIMP-1 levels were found to be significantly increased in patients with preoperative CRP>12 mg/L and in those who died from rectal cancer or had cT4 tumors. No correlation was established for age, gender, CEA level, platelets count, histopathological grade and response to preoperative therapy, resectability and disease re-appearance. On univariate analysis, various parameters favorably influenced one or more survival endpoints: TIMP-1 <170 ng/mL, CRP <12 mg/L, platelets count <290 10E9/L, CEA <3.4mg/L, age <69 years, male gender, early stage disease (cN0 and/or cT2-3), radical surgery (R0) and response and results to preoperative radiochemotherapy. In multivariate model, LRC was favorably influenced by N-downstage, DFS by lower CRP and N-downstage, DSS by lower CRP and N-downstage and OS by lower TIMP-1 level, lower CRP and N-downstage.
Conclusion: Although we did not find any association between pretreatment serum TIMP-1 levels and primary tumor response to preoperative radiochemotherapy in our cohort of patients with rectal cancer, TIMP-1 levels were recognized as an independent prognostic factor for OS in these patients.