TUMOR VASCULARITY - A NOVEL PROGNOSTIC FACTOR IN ADVANCED CERVICAL-CARCINOMA

Objective: In the search for the optimal treatment of advanced cervica l cancer, the identification of valid prognostic factors obtainable wi thout histopathologic investigation of the entire tumor and the locore gional lymph nodes is of paramount interest. Tumor microvessel density has recently been demonstrated to correlate strongly with disease agg ressiveness in breast cancer and other malignancies. Methods: We estab lished a computerized image analysis system to quantify tumor microvas cularity by using the closest-individual method, which determines the distribution of distances from random points within the tumor to the c losest microvessel (DTCMV). Tumor microvascularity was assessed in par affin sections of two cylindrical 2 x 20-mm core biopsies obtained tra nsvaginally from the 12 and 6 o'clock positions of each tumor and then immunohistochemically stained for Factor VIII-related antigen. The on cologic relevance of tumor vascularity is studied in an open prospecti ve trial. Results: Tumor vascularity was quantified in 42 patients wit h cervical cancers >3 cm in largest diameter, FIGO stages Ib-IVa. This new parameter representing pathophysiological tumor-host interactions was independent of various other patient and tumor characteristics, i ncluding age, FIGO stage, tumor size, differentiation, lymph node meta stases and lymphatic space involvement. Thirty-nine patients were trea ted with curative intent either by primary surgery (n = 22) or radiati on (n = 17), After a median observation time of 18 months (range 4-41 months), the patients with higher tumor vascularity (mean DTCMV <83 mu m) had significantly shorter disease-free (P = 0.025) and overall (P = 0.032) survival probabilities than patients with lower tumor vascula rity (mean DTCMV greater than or equal to 83 mu m). Cox regression ana lysis identified tumor vascularity as the strongest independent progno stic factor in this group of patients. Conclusions: The assessment of tumor microvascularity by computerized image analysis of defined tumor biopsies could become a novel means of predicting tumor aggressivenes s in non-early cervical cancer. (C) 1995 Academic Press, Inc.