title: Beta-fibroblast growth factor expression in human and murine squamous cell carcinomas and its relationship to regional endothelial cell proliferation.
abstract: Surgical biopsies from ten head and neck squamous cell carcinomas were labeled in vitro with bromodeoxyuridine. In histological sections, bromodeoxyuridine-positive nuclei and beta-fibroblast growth factor (beta-FGF) were stained using immunohistochemistry. In clearly discernible clusters of tumor cells, the cytoplasm shows strong positive beta-FGF staining, whereas other tumor regions are completely beta-FGF negative. Within positively stained areas, the tumor cell bromodeoxyuridine labeling index is higher in comparison to beta-FGF-negative areas by a factor of 5 +/- 0.8. This is reflected in a positive correlation of the tumor cell labeling index and the relative extent of beta-FGF-positive tumor areas. Viable tumor areas bordering on necrosis, which are known to be hypoxic, are beta-FGF negative. The average tumor endothelial cell labeling index was 1.8 +/- 0.6%, as compared to 0.16% in adjacent normal mucosa. Since endothelial cell pulse labeling indices are too low for a further quantitative analysis, the relationship of beta-FGF expression and endothelial cell turnover was studied in more detail in two fairly well-differentiated murine squamous cell carcinoma lines (AT 84 and AT 478). Labeling indices were higher and endothelial cell doubling times were significantly shorter in beta-FGF-positive as compared to beta-FGF-negative tumor areas (AT 84, 9.3 h versus 25.4 h; AT 478/25, 6.8 h versus 16 h). Thus, the discrete expression of beta-FGF is associated with regional differences in endothelial cell kinetics. In two generations of the tumor line AT 478, characterized by different volume doubling times of 18 days (AT 478/25) and 36 days (AT 478/4), beta-FGF-positive areas represent 75.5 +/- 6% and 19.7 +/- 7% of the viable tumor tissue, respectively. This indicates a correlation between beta-FGF production of tumor cells and growth rate.
authors.affiliation: GSF-Institut f. Strahlenbiologie, Neuherberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Schultz-Hector
authors.forename: S
authors.initials: S
authors.lastname: Haghayegh
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000473:pathology; D002455:Cell Division; D004730:Endothelium, Vascular / Q000737:chemistry / Q000473:pathology*; D016222:Fibroblast Growth Factor 2 / Q000032:analysis*; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D009389:Neovascularization, Pathologic; D014407:Tumor Cells, Cultured
chemical_list: D016222:Fibroblast Growth Factor 2