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Morphometric Evaluation of Tumor Matrix Metalloproteinase 9 Predicts Survival after Surgical Resection of Adenocarcinoma of the Lung¹

Department of Pathology [C. A. P., F. S.] and Thoracic Surgery of Hospital do Câncer AC Camargo [R. Y.] and Marilia Medical School [P. E. d. O. C.] and Departments of Thoracic Surgery [R. B.], Oncology [T. T.], and Pathology [L. A., A. G., A. G. P. d. S., P. S., V. L. C.], School of Medicine, University of São Paulo, São Paulo, Brazil, and Duke University and VA Medical Centers, Durham, North Carolina 27705 [R. T. V.]

Purpose: Recently, several matrix metalloproteinases (MMPs) have shown promise as prognosticators in non-small cell lung cancer. In this study, we sought to validate the importance of MMP-9 and to study the relationships between MMP-9 and several other tumor or stromal markers.

Experimental Design: We examined MMP-9 and several other markers in tumor tissues from 152 patients with surgically excised adenocarcinomas of the lung. Their preoperative clinical stages were T_1–4N₀M₀; however, pathological exam of their resected tissues demonstrated that 33 were stage II, and 64 were stage III. We used immunohistochemistry and morphometry to evaluate the amount of tumor staining for MMP-9, and the outcome for our study was survival time until death from recurrent lung cancer.

Results: Multivariate Cox model analysis demonstrated that pathological stage was significantly related to survival time (P < 0.01), but quantitative staining of the tumor for MMP-9 added prognostic information (P < 3.0 x10^-16) and was more strongly prognostic than pathological stage. In the subset of pathological stage I patients, staining for MMP-9 was also significantly associated with survival (P < 1.0 x10^-6), and a cutpoint at the median staining of 11.2% for MMP-9 divided them into two groups with distinctive survival times. Those with MMP-9 > 11.2% had a median survival time of just 11 months. Those with MMP-9 < 11.2% had not reached a median survival and had a mean survival time of >62 months.

Conclusions: Tumor staining for MMP-9 in resected adenocarcinoma of the lung is strongly related to survival. Patients with >11.2% staining in their tumors comprise a subset with a high hazard for dying of lung cancer and may be an appropriate target for prospective studies of adjuvant chemotherapy after surgical resection.

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