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 (TIMP s) are important in tumor development and progression. MMP expression has b een correlated with advanced clinical stage and poor survival in some tumor s, 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 evaluat e their importance relative ta standard prognostic factors, Patients and Methods: Expression of MMP-1, -2, -3, -9, -11, -13, and -14 an d TIMP-1, -2, -3, and -4 was evaluated by immunohistochemistry (IHC). In si tu hybridization wets used to confirm expression of specific mRNAs. Clinica l 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 performa nce status 0-1. Positive IHC staining was evident for MMP-1 and -9 in 60% t o 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 l ess thorn 30% of specimens. On multivariate analysis, only stage and decrea sed 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 signi ficantly between stages, Conclusion: MMPs and TIMPs are widely expressed in SCLC. Increased tumoral expression of MMP-3, -11, and -14 were independent negative prognostic fact ors for survival. The results support the evaluation of synthetic MMP inhib itors in patients with SCLC. (C) 1999 by American Society of Clinical Oncol ogy.