Background: Interstitial cells of Cajal (ICCs) are claimed to be involvedin gut electromotor activity. We investigated whether absent or diminished ICCs in the esophagogastricjunction (EGJ) may be responsible for EGJ incompetence in gastro-esophageal reflux disease (GERD). Material/Methods:Endoscopic specimens were obtained from the upper and mid third of the esophagus and from the EGJ of29 patients (17 men, 12 women, mean age: 46.7 years) with GERD (5 grade A, 5 B, 6 C, and 13 D, Los Angelesclassification) and from 8 controls. Sections were prepared for inmunohistochemical investigation usingan ICC marker c-kit. Controls had normal rabbit serum substituted for the primary antiserum. Results:C-kit-positive branched ICC-like cells were detected in the esophageal and EGJ musculature of the controls.They were distinguishable from the c-kit-negative unbranched smooth muscle cells and from the c-kit-positiveunbranched mast cells. Immunoreactivity was absent in the negative controls. ICCs in the esophageal bodyexisted in GERD and in controls, but were absent from the EGJ of 12 patients (2 grade C, 10 D) and occasionallydetected in 5 of group A, 5 of B, 4 of C, and 3 of group D patients. Conclusions: ICCs were demonstratedin the esophageal body and EGJ of controls. In GERD patients they were detected in the esophageal body,but were deficient or absent in the EGJ. It is postulated that ICC absence or deficiency is responsiblefor EGJ incompetence and GER. The cause of ICC deficiency or absence needs to be investigated.

Keywords: Esophagitis, Peptic - pathology, Esophagogastric Junction - pathology, Esophagus - pathology, Gastroesophageal Reflux - pathology, Proto-Oncogene Proteins c-kit - analysis