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(American Journal of Pathology. 2001;159:2125-2135.)
© 2001 American Society for Investigative Pathology

Regular Article

Expression of Matrix Metalloproteinases in Invasive Pulmonary Adenocarcinoma with Bronchioloalveolar Component and Atypical Adenomatous Hyperplasia

Fumiyuki Kumaki^*, Kazuhiro Matsui, Toshiaki Kawai^*, Yuichi Ozeki, Zu-Xi Yu, Victor J. Ferrans and William D. Travis

From the Departments of Pathology and Thoracic Surgery,^*
National Defense Medical College, Tokorozawa, Saitama, Japan; the Pathology Section,
National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland; and the Department of Pulmonary and Mediastinal Pathology,
Armed Forces Institute of Pathology, Washington, District of Columbia

To investigate the association between the expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) and the clinicopathological features in lepidic and invasive components of adenocarcinoma of the lung, we performed immunostaining for type IV collagen, various MMPs, and TIMPs in 27 cases of invasive adenocarcinomas and 5 cases of atypical adenomatous hyperplasia of alveolar epithelial cells (AAH). Mean extent of lepidic growth was 61% and the survival was significantly better in cases with 50% or more lepidic component. The preservation of type IV collagen in lepidic areas correlated inversely with lymphatic or vascular invasion (P = 0.02 and 0.002, respectively). Five-year survival was reduced in cases showing destruction of type IV collagen (P = 0.004) or expression of MMP-2 (P = 0.008) in lepidic areas. MMP-2 co-localized with MT-1-MMP (its activating enzyme) and TIMP-2 in neoplastic cells. Reactivity for other MMPs and TIMPs did not correlate with destruction of type IV collagen or prognosis. Type IV collagen was preserved in all cases of AAH. MMP-2, but not MT-1-MMP, was expressed in two of the five cases of AAH. Immunostaining for type IV collagen MMP-2 is useful in evaluating the prognosis of the lung.

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