SPECTRUM OF GLANDULAR DIFFERENTIATION IN EXPERIMENTAL CARCINOMA OF THE ESOPHAGUS INDUCED BY 2,6-DIMETHYLNITROSOMORPHOLINE UNDER THE INFLUENCE OF ESOPHAGOJEJUNOSTOMY

To investigate the influence of reflux esophagitis (RE) on the glandular differentiation of carcinomas of the esophagus induced by 2,6-dimethylnitrosomorpholine (2,6-DMNM), a study was carried out using 4 experimental groups and 2 control groups of 8-week-old Sprague-Dawley rats, each consisting of 20 males and 20 females. An esophagojejunostomy (EJ) with gastric preservation was performed in two groups of animals. Fifteen days thereafter the potent esophagotropic carcinogen 2,6-DMNM was subcutaneously injected, once a week for Life, at doses of 1/100 and 1/10 of the 50% lethal dose in each group respectively. The result was a spectrum of carcinomatous tumors mainly developing in the lower half of the esophagus, which were thoroughly investigated by serial sectioning, staining for mucins, and in selected cases by electron microscopy. They were classified as follows: 16 pure squamous cell carcinomas (SCC), 5 SCC with focal mucous or glandular differentiation (FGD), 11 pure adenocarcinomas (ADC), and 12 ADC with areas of squamous cell differentiation (SCD). By contrast, in 2 similar experimental groups in which the previous EJ was not performed, 15 animals showed SCC of the pure type, without evidence of mucous or glandular differentiation. No tumors were observed in the two control groups without carcinogen treatment. Of these, the group that underwent EJ showed reflux esophagitis. In conclusion, the tumors of the esophagus induced by 2,6 DMNM under the influence of EJ are not only pure ADC and pure SCC, as we have previously reported, but also intermediate tumors showing either SCC with focal mucous or glandular differentiation (SCC + FGD) or ADC with areas of squamous cell differentiation (ADC + SCD). These intermediate tumors resemble the adenosquamous carcinoma of the esophagus seen in humans.