Expression and prognostic significance of metalloproteinases and their tissue inhibitors in patients with small-cell lung cancer

Purpose: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are important in tumor development and progression. MMP expression has been correlated with advanced clinical stage and poor survival in some tumors, bur data for small-cell lung cancer (SCLC) are lacking. The aim ob this study was to assess the expression of MMPs and TIMPs in SCLC and to evaluate their importance relative ta standard prognostic factors, Patients and Methods: Expression of MMP-1, -2, -3, -9, -11, -13, and -14 and TIMP-1, -2, -3, and -4 was evaluated by immunohistochemistry (IHC). In situ hybridization wets used to confirm expression of specific mRNAs. Clinical data collected included sex, tumor stage, performance status, weight loss, hematology (hemoglobin, WBC, platelets) and biochemistry (sodium, albumin, alkaline phosphatase, lactate dehydrogenase), treatment, and survival, Results: Samples from 46 patients were evaluated: 30 males, 16 females: 29 limited, 17 extensive stage; 35 Eastern Cooperative Oncology Group performance status 0-1. Positive IHC staining was evident for MMP-1 and -9 in 60% to 70% of tumor cells, and for MMP-1 a, -13, and -14 and TIMP-2 and -3 in 70% to 100% of tumor cells, Stromal staining of TIMP-1 to -3 was present in less thorn 30% of specimens. On multivariate analysis, only stage and decreased tumoral expression of TIMP-1 were significant for response (P = .043), Significant factors for survival were tumor stage (P = .0021); weight loss (P = .013); and high tumor cell expression of MMP-3 (P = .077), MMP-11 (P = .031), and MMP-14 (P = .019), MMP and TIMP expression did not differ significantly between stages, Conclusion: MMPs and TIMPs are widely expressed in SCLC. Increased tumoral expression of MMP-3, -11, and -14 were independent negative prognostic factors for survival. The results support the evaluation of synthetic MMP inhibitors in patients with SCLC. (C) 1999 by American Society of Clinical Oncology.