Pseudomyxoma peritonei: is disease progression related to microbial agents? A study of bacteria, MUC2 AND MUC5AC expression in disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis.
OBJECTIVE
Pseudomyxoma peritonei (PMP) is characterized by peritoneal tumors arising from a perforated appendiceal adenoma or adenocarcinoma, but associated entry of enteric bacteria in the peritoneum has not been considered as a cofactor. Because Gram-negative organisms can upregulate MUC2 mucin gene expression, we determined whether bacteria were detectable in PMP tissues.


METHODS
In situ hybridization was performed on resection specimens from five control subjects with noninflamed, nonperforated, non-neoplastic appendix and 16 patients with PMP [six with disseminated peritoneal adenomucinosis (DPAM) and 10 with peritoneal mucinous carcinomatosis (PMCA)]. Specific probes were designed to recognize: (1) 16S rRNA common to multiple bacteria or specific to H. pylori; (2) H. pylori cagA virulence gene; or (3) MUC2 or MUC5AC apomucins. Specimens from one patient with PMCA were examined by ultrastructural immunohistochemistry. Bacterial density and apomucin expression were determined in four histopathological compartments (epithelia, inflammatory cells, stroma, and free mucus).


RESULTS
Enteric bacteria were detected in all specimens. Bacterial density and MUC2 expression were significantly (p < 0.05) higher in PMCA than in DPAM and controls and were highest in free mucin. MUC2 was also expressed in dysplastic epithelia and in associated inflammatory cells. MUC2 expression was significantly correlated with bacterial density.


CONCLUSIONS
Multiple enteric bacteria are present in PMP, and bacterial density and MUC2 expression is highest in the malignant form of PMP. Based on these observations, we propose that the bacteria observed in PMP may play a role in the mucinous ascites and perhaps promote carcinogenesis.
Semino-Mora
Cristina
C
Laboratory of Gastrointestinal and Liver Studies, Department of Medicine, Uniformed Services University and United States Military Cancer Institute, Bethesda, MD 20814, USA.
Liu
Hui
H
McAvoy
Thomas
T
Nieroda
Carol
C
Studeman
Kimberley
K
Sardi
Armando
A
Dubois
Andre
A
D002288:Adenocarcinoma, Mucinous / Q000378:metabolism / Q000382:microbiology; D001065:Appendix / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D015342:DNA Probes; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D016481:Helicobacter Infections / Q000378:metabolism / Q000382:microbiology*; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D017403:In Situ Hybridization; D046529:Microscopy, Electron, Transmission; D055271:Mucin 5AC; D055262:Mucin-2; D009077:Mucins / Q000235:genetics / Q000378:metabolism*; D010534:Peritoneal Neoplasms / Q000378:metabolism / Q000382:microbiology*; D011379:Prognosis; D011553:Pseudomyxoma Peritonei / Q000378:metabolism / Q000382:microbiology*; D015347:RNA Probes
D014408:Biomarkers, Tumor; D015342:DNA Probes; C524625:MUC2 protein, human; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D055262:Mucin-2; D009077:Mucins; D015347:RNA Probes