Patterns of proliferation related to vasculature in human head-and-neck carcinomas before and after transplantation in nude mice

Purpose: The predictive potential of tumor cell kinetic parameters may be i mproved when they are studied in relation to other microenvironmental param eters. The purpose of this investigation was to quantitatively categorize h uman tumor samples according to proliferation patterns. Second, it was exam ined whether these characteristics are retained after xenotransplantation. Methods and Materials: Fifty tumor samples from head-and-neck cancer patien ts were immunohistochemically stained for Ki-67 and-vessels. Also, parts of the samples were transplanted into nude mice. Tumors were categorized acco rding to previously described patterns of proliferation. Vascular and proli feration patterns were analyzed using an image processing system. Results: The 50 tumors were categorized into four patterns of proliferation by visual assessment: marginal (6), intermediate (10), random (21), and mi xed (12). One tumor could not be classified. These patterns were quantified by calculating the Ki-67 labeling index in distinct zones at increasing di stance from vessels yielding good discrimination and significant difference s between patterns. The probability of growth after xenotransplantation was significantly higher for tumors with a labeling index and vascular density above the median value compared to tumors with both parameters below the m edian (82% vs. 35%). Fifty percent of the tumors retained their proliferati on patterns after xenotransplantation. Conclusion: The categorization by proliferation pattern previously describe d by others was reproduced quantitatively and spatially related to the vasc ular network using a computerized image processing system. The combination of quantitative and architectural information of multiple microenvironmenta l parameters adds a new dimension to the study of treatment resistance mech anisms. Tumor models representative of the various patterns can be used to further investigate the relevance of these architectural patterns. (C) 2001 Elsevier Science Inc.