Estrogens influence the natural history of Sinclair swine cutaneous melanoma

Initial results (Cancer Res., 48: 1708-1711, 1988) suggest that ovariectomy alters the proliferation of congenital exophytic melanoma in Sinclair swine. In order to provide a phenotypic basis for this effect, histopathological staging of 375 exophytic melanomas from 236 intact male and female Sinclair swine was compared with 114 lesions from 51 gonadectomized (6 weeks of age) and 90 lesions from castrated swine receiving s.c. silastic implants of estradiol during the first year of life. A rapid progression from actively proliferating tumor cells (Stages I-III) to regressive lesions (Stages IV-V) was virtually complete by 16 weeks of age in intact swine of both sexes. Bilateral ovariectomy reduced (P less than 0.02) tumor volume over time compared with intact animals. Replacement of estradiol in gilts increased tumor volume to that in intact animals. In contrast, neither bilateral orchidectomy nor estradiol replacement altered tumor volume in boars. Ovariectomy significantly reduced the tumor macrophage, keratinocyte, and fibroblast invasion that normally replaces tumor cells and expands tumor volume (Stages IV and V) with increasing age. Chronic exposure to estradiol reversed this process. Orchidectomy and estradiol replacement did not significantly affect histopathological stage in boars with increasing age. A significant number (20 of 41; 49%) of Stage III lesions (greater than 75% tumor cells) in swine of both sexes contained low but reproducibly measurable amounts of receptor for estrogen determined radiometrically and by enzyme-linked immunosorbent assay. These results suggest that reproductive steroids influence the natural history of these heritable lesions, and that the effect may be via alteration of host immune status.