CHRONIC ESOPHAGITIS EVOLVING TO VERRUCOUS SQUAMOUS-CELL CARCINOMA - POSSIBLE ROLE OF EXOGENOUS CHEMICAL CARCINOGENS

Background & Aims: A patient exposed to aerosolized lye and ingested k erosene was followed up for 16 years with chronic esophagitis before d eveloping verrucous esophageal squamous carcinoma, The aim of this stu dy was to elucidate the pathogenesis of the carcinoma, Methods: Multip le biopsy specimens were graded according to the severity of esophagit is and dysplasia, Molecular biological techniques and immunocytologica l assay were used to look for human papillomavirus infection, p53 muta tions, loss of heterozygosity for TP53 and chromosome 8 markers, and r as mutations, Results: Morphological features of the chronic esophagit is in this patient were similar to the precancerous lesions from high- risk areas for esophageal squamous cancer and the precancerous lesions induced in rats by N-methyl-N-nitrosoaniline. Gastroesophageal acid r eflux and human papillomavirus infection were ruled out, No loss of he terozygosity of p53 or for chromosome 8 markers was found. Mutations o f the ras oncogene were not identified, By immunocytological assay ove rexpression of p53 was identified only in the invasive portion of the carcinoma, Conclusions: In this patient, verrucous squamous carcinoma evolved from chronic esophagitis, squamous papillary hyperplasia, and dysplasia, Although exogenous carcinogens may have been important, the y probably did not act by causing loss of heterozygosity or ras mutati ons, p53 overexpression occurred late.