DEFECTIVE BASEMENT-MEMBRANE IN LARYNGEAL CARCINOMAS WITH HETEROGENEOUS LOSS OF DISTINCT COMPONENTS

In this study, we evaluated immunohistochemically the composition of t he tumor-associated epithelial basement membrane (BM) in a series of 6 6 laryngeal squamous cell carcinomas (SCC) and compared these results with those from 10 cases with laryngeal dysplasia and five cases with normal mucosa (controls). The major BM components collagen IV and VII, laminin-l, perlecan (heparan sulfate proteoglycan), and fibronectin w ere evaluated. The extent of the retained BM material was quantified b y semiautomated morphometry. A subsequent statistical analysis correla ted the immunohistochemical findings with the histopathologically eval uated degree of tumor cell differentiation. In our series, we observed a distinct correlation between the degree of tumor cell differentiati on and the amount of retained BM material. The loss of BM affected the various components differently with a more extensive loss of collagen VII even in highly differentiated tumors and a progressive loss of co llagen IV immunostaining with decreasing tumor cell differentiation. W ith respect to the other BM components, a stepwise loss of BM material also was seen with decreasing degree of the tumor cell differentiatio n. This loss, however was not at a statistically significant level, so these parameters did not show further statistically relevant data. In dysplastic lesions (regardless of the degree of dysplasia), focal BM disruptions were seen that affected the various BM components to a ver y similar extent. Our observations provide evidence that laryngeal car cinomas show a progressive loss of BM material along with decreasing t umor cell differentiation. This loss of BM, however, affects the vario us BM components differently. This indicates a dysregulation of the BM , either induced by uncoordinated neosynthesis or selectively enhanced degradation by proteases or both. Finally, the Bill analysis may prov ide information on the biological course of the tumors. The loss of co llagen VII may serve as a marker for ''early'' invasive tumor growth, whereas the amount of collagen IV provides significant information on the loss of tumor cell differentiation. Copyright (C) 1998 by W.B. Sau nders Company.