Overexpression of matrix metalloproteinase 2 predicts unfavorable outcome in early-stage non-small cell lung cancer.

This prospective study was performed to assess the impact of matrix metalloproteinase (MMP) 2 expression on the clinical course of patients with operable non-small cell lung cancer (NSCLC). Specimens of 193 consecutive patients with completely resected NSCLC were examined for MMP-2 expression by immunohistochemical staining with a polyclonal antibody. Homogeneous immunostaining of cancer cells was considered positive and heterogeneous, or no staining was considered negative concerning overexpression of MMP-2. Four specimens were excluded from further analyses because of unspecific staining. The median follow-up period was 71.5 months (range, 12-120 months). Overexpression of MMP-2 was observed in 64 (33.9%) of 189 patients and did not correlate with clinicopathoiogical parameters. In patients without lymph node involvement (pN0 stage) MMP-2 overexpression was an independent prognostic parameter for unfavorable outcome: Log-rank analysis showed a significant association of MMP-2 overexpression with shortened cancer-related survival (P = 0.04) and disease-free survival (P = 0.03). Multivariate regression analysis confirmed MMP-2 overexpression as predictor of shortened cancer-related survival in NSCLC without lymph node involvement (P = 0.005, relative risk, 2.6). The present study revealed that MMP-2 overexpression predicts a poor prognosis in early-stage NSCLC. Therefore, it might be worth investigating the role of MMP inhibitors as adjuvant therapeutic agents in NSCLC.

The 17-1A antigen is expressed on primary, metastatic and disseminated non-small cell lung carcinoma cells.

In view of the high incidence of early distant tumor relapses in apparently completely resected (R0, M0) non-small cell lung cancer (NSCLC), there is a need for an adjuvant therapy. Considering the low tumor burden in these patients, an adjuvant therapy with monoclonal antibodies (i.e., the 17-1A MAb) might be appropriate. The purpose of our study was to test whether the 17-1A antigen is expressed on primary and metastatic NSCLC carcinoma cells. Using immunohistochemistry, the expression of 17-1A was analysed in primary tumors (n = 60) and in lymph node metastases (n = 7) of patients with NSCLC. Additionally, we investigated in 6 patients the expression of 17-1A on disseminated tumor cells in the bone marrow, which were detected by the pan-cytokeratin MAb A45-B/B3 using a double-labeling technique. The 17-1A antigen was homogeneously expressed in 47 (78.3%) out of 60 primary NSCLCs. The expression of 17-1A was independent from the tumor histology, the grade of differentiation, and other clinicopathological parameters (ploidy status, TNM-stage). Lymph node metastases were positive in 4 (57.4%) out of 7 cases. The double-labeling experiments demonstrated that 17-1A is coexpressed on disseminated tumor cells in the bone marrow in 5 (83%) out of 6 patients. The 17-1A antigen is expressed on the majority of primary, metastatic, and disseminated NSCLC cells. Patients with 17-1A-positive tumors might benefit from an adjuvant therapy with MAb 17-1A after completely resected NSCLC.

Reduced expression of plakoglobin indicates an unfavorable prognosis in subsets of patients with non-small-cell lung cancer.

PURPOSE: Plakoglobin is thought to play a key role in cadherin-mediated epithelial cell adhesion, because it is a common component of desmosomal and nondesmosomal adherens junctions. Because loss of homotypic cell adhesion is an important early step in invasion and metastasis of solid tumors, we evaluated the frequency and prognostic significance of a deficient expression of plakoglobin in human lung cancer. PATIENTS AND METHODS: At primary surgery, representative specimens of the primary tumor were obtained from 96 consecutive patients with completely resected non-small-cell lung carcinoma (NSCLC) without overt distant metastases. Cryostat sections of these specimens and metastatic lymph nodes were stained with monoclonal antibody (mAb) PG 5.1 against plakoglobin, using an immunoperoxidase technique. Patients were monitored for a median of 39 months (range, 12 to 56) after surgery. RESULTS: Absent or severely reduced expression of plakoglobin (ie, < 30% positive tumor cells) was observed in 39 patients (40.6%). There was no significant correlation to established risk factors, such as the histology, extension, and histologic grade of the primary tumor and metastatic lymph node involvement, or expression of alpha-catenin. Expression of plakoglobin in lymph node metastases ranged from 0% to greater than 60% positive tumor cells. Deficient plakoglobin expression on the primary tumor was significantly correlated to a shortened disease-free and overall survival in patients with adenocarcinomas, pT1-2 tumors, or negative lymph nodes (pN0). In patients with pT1-2 tumors, the independence of this prognostic influence from established risk factors was demonstrated by Cox regression analyses (disease-free survival, P = .002; overall survival, P = .038). CONCLUSION: Deficient expression of plakoglobin appears to be an important event in the progression of NSCLC.