Cancer Therapy : Clinical Antibiotic Treatment Decreases Microbial Burden Associated with Pseudomyxoma Peritonei and Affects b-Catenin Distribution

Purpose: Pseudomyxoma peritonei is an understudied cancer in which an appendiceal neoplasm invades the peritoneum and forms tumor foci on abdominal organs. Previous studies have shown that bacteria reside within pseudomyxoma peritonei tumors andmucin. Thus, we sought to analyze the effect of antibiotics on bacterial density and b-catenin expression within pseudomyxoma peritonei samples. ExperimentalDesign: The study included 48patients: 19with disseminated peritoneal adenomucinosis (DPAM)and29withperitonealmucinous carcinomatosis (PMCA). Fourteenpatientswere given antibiotics (30 mg lansoprazole, 1 g amoxicillin, and 500 mg clarithromycin) twice a day for 14 days. One week after completion of therapy, surgery was conducted and specimens were harvested for pathology, bacterial culture, ISH, and immunohistochemistry. Results: ISH showed the presence of bacteria in 83% of the patient samples, with a higher Helicobacter pylori density observed in PMCA versus DPAM. PMCA patients treated with antibiotics had a significantly lower bacterial density anddecreasedb-catenin levels in the cytoplasm, the cell nuclei, andmucin-associated cells. Although not significant, similar trends were observed in DPAM patients. Cell membrane b-catenin was significantly increased in both DPAM and PMCA patients receiving antibiotics. Conclusions: Bacteria play an important role in pseudomyxoma peritonei. Antibiotic treatment improved the histopathology of tissue, particularly in PMCA patients. In PMCA, antibiotics decreased bacterial density and were associated with a significant b-catenin decrease in the cytoplasm, cell nuclei, and mucin along with a small membrane increase. These results suggest that antibiotics offer potential protection against cell detachment, cellular invasion, and metastasis. Clin Cancer Res; 19(14); 3966–76.