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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

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background and Aims

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.

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ACKNOWLEDGMENTS

Supported in part by National Institutes of Health grant CA82312, USUHS grant HU83KT funded by an unrestricted gift in memory of Jessie McAvoy, and the E. Allen Davis Memorial fund. This paper is dedicated to the memory of Jessie McAvoy.

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Authors and Affiliations

  1. Laboratory of Gastrointestinal and Liver Studies, Department of Medicine, Uniformed Services University and United States Military Cancer Institute, Bethesda, MD, 20814, USA

    Cristina Semino-Mora, Hui Liu, Thomas McAvoy, Carol Nieroda & Andre Dubois

  2. University of Maryland, College Park, MD, 20742, USA

    Thomas McAvoy

  3. Mercy Health Services, Baltimore, MD, 21202, USA

    Carol Nieroda, Kimberley Studeman & Armando Sardi

Authors
  1. Cristina Semino-Mora
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  2. Hui Liu
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  3. Thomas McAvoy
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  4. Carol Nieroda
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  5. Kimberley Studeman
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  6. Armando Sardi
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  7. Andre Dubois
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Correspondence to Andre Dubois.

Additional information

Presented in part at the Society of Surgical Oncology, Cancer Symposium. March 23-26, 2006, San Diego, California.

None of the authors have any financial and personal relationship with others that might bias their work, and potential conflicts do not exist.

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Semino-Mora, C., Liu, H., McAvoy, T. et al. 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. Ann Surg Oncol 15, 1414–1423 (2008). https://doi.org/10.1245/s10434-007-9778-9

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