Malignant progression of papillomas induced by the initiation--promotion protocol in NMRI mouse skin

Recording of individual responses to initiation-promotion was used to study the relationship between papilloma and carcinoma formation in NMRI mouse skin. This type of analysis is without precedent in that it allows a statistical evaluation of the data which was impossible with previously published analyses based upon cumulative tumor response data evaluated in other mouse strains. Initiation with DMBA and promotion with TPA yielded papillomas consisting of two sub-populations, reversible and persistent papillomas. The ratio of persisting to reversible papillomas was independent of the duration of promotion, indicating comparable growth rates for both types of papillomas. Fifty percent of the persistent and 4% of all papillomas progressed into carcinomas. Promotion for > 20 weeks increased neither the total number of papillomas nor the number of carcinomas. Both the maximum number of persistent and the maximum number of reversible papillomas correlated with the risk of malignant progression, excluding persistent papillomas as being the exclusive precursor lesions for malignant progression.