Flow cytometry and Zollinger-Ellison syndrome: Relationship to clinical course

Abstract

Background: With successful means of controlling gastric acid secretion in patients with Zollinger-Ellison syndrome, the gastrinoma itself is becoming the major determinant of long-term survival. No methods have yet been described to predict which tumors will have more malignant courses thereby indicating which patients should undergo aggressive surgery or antitumor therapy. Because DNA analysis, using flow cytometry, has proved helpful in this regard in other tumors, the current study was designed to evaluate its utility in gastrinoma patients. Methods: Flow cytometry was performed on 81 paraffin-embedded gastrinoma specimens from 59 patients. Results were compared with preoperative patient characteristics, findings at surgery, and postoperative follow up. Results: Tumors were diploid in 54% of patients, near diploid in 15%, pure tetraploid in 0%, nontetraploid aneuploid in 25%, and multiple stem line aneuploid in 5%. All patients with multiple stem line aneuploid tumors had widespread metastases whereas all patients with nontetraploid aneuploid tumors had localized or regional disease. Median S phase percentage was 3.6. S phase percentages were higher in patients with widespread metastatic disease than in patients with localized or regional disease. Disease extent also correlated closely with fasting serum gastrin level. After removing this variable with logistic regression analysis, the significant correlation between disease extent and DNA analysis persisted. Conclusions: DNA analysis of gastrinoma tissue specimens correlates independently with the extent of disease and may be useful in planning therapeutic strategies for patients with Zollinger-Ellison syndrome.