Skip to main content
Top
Published in: Annals of Surgical Oncology 5/2008

01-05-2008 | Gastrointestinal Oncology

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

Authors: Cristina Semino-Mora, Hui Liu, Thomas McAvoy, Carol Nieroda, Kimberley Studeman, Armando Sardi, Andre Dubois

Published in: Annals of Surgical Oncology | Issue 5/2008

Login to get access

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.
Literature
1.
go back to reference Bradley RF, Stewart JH, Russell GB, et al. Pseudomyxoma peritonei of appendiceal origin: a clinicopathologic analysis of 101 patients uniformly treated at a single institution, with literature review. Am J Surg Pathol 2006;30:551–9PubMedCrossRef Bradley RF, Stewart JH, Russell GB, et al. Pseudomyxoma peritonei of appendiceal origin: a clinicopathologic analysis of 101 patients uniformly treated at a single institution, with literature review. Am J Surg Pathol 2006;30:551–9PubMedCrossRef
2.
go back to reference Mann WJ Jr., Wagner J, Chumas J, et al. The management of pseudomyxoma peritonei. Cancer 1990;66:1636–40PubMedCrossRef Mann WJ Jr., Wagner J, Chumas J, et al. The management of pseudomyxoma peritonei. Cancer 1990;66:1636–40PubMedCrossRef
3.
go back to reference Aho AJ, Heinonen R, Lauren P. Benign and malignant mucocele of the appendix. Histological types and prognosis. Acta Chir Scand 1973;139:392–400PubMed Aho AJ, Heinonen R, Lauren P. Benign and malignant mucocele of the appendix. Histological types and prognosis. Acta Chir Scand 1973;139:392–400PubMed
4.
go back to reference Witkamp AJ, de Bree E, Kaag MM, van Slooten GW, van CF, Zoetmulder FA. Extensive surgical cytoreduction and intraoperative hyperthermic intraperitoneal chemotherapy in patients with pseudomyxoma peritonei. Br J Surg 2001;88:458–63PubMedCrossRef Witkamp AJ, de Bree E, Kaag MM, van Slooten GW, van CF, Zoetmulder FA. Extensive surgical cytoreduction and intraoperative hyperthermic intraperitoneal chemotherapy in patients with pseudomyxoma peritonei. Br J Surg 2001;88:458–63PubMedCrossRef
5.
go back to reference Galani E, Marx GM, Steer CB, et al. Pseudomyxoma peritonei: the ‘controversial’ disease. Int J Gynecol Cancer 2003;13:413–8PubMedCrossRef Galani E, Marx GM, Steer CB, et al. Pseudomyxoma peritonei: the ‘controversial’ disease. Int J Gynecol Cancer 2003;13:413–8PubMedCrossRef
6.
go back to reference Loungnarath R, Causeret S, Bossard N, et al. Cytoreductive surgery with intraperitoneal chemohyperthermia for the treatment of pseudomyxoma peritonei: a prospective study. Dis Colon Rectum 2005;48:1372–9PubMedCrossRef Loungnarath R, Causeret S, Bossard N, et al. Cytoreductive surgery with intraperitoneal chemohyperthermia for the treatment of pseudomyxoma peritonei: a prospective study. Dis Colon Rectum 2005;48:1372–9PubMedCrossRef
7.
go back to reference Loungnarath R, Causeret S, Brigand C, et al. [Pseudomyxoma peritonei: new concept and new therapeutic approach]. Ann Chir 2005;130:63–9PubMedCrossRef Loungnarath R, Causeret S, Brigand C, et al. [Pseudomyxoma peritonei: new concept and new therapeutic approach]. Ann Chir 2005;130:63–9PubMedCrossRef
8.
go back to reference Levine EA, Stewart JH, Russell GB, et al. Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy for peritoneal surface malignancy: experience with 501 procedures. J Am Coll Surg 2007;204:943–53PubMedCrossRef Levine EA, Stewart JH, Russell GB, et al. Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy for peritoneal surface malignancy: experience with 501 procedures. J Am Coll Surg 2007;204:943–53PubMedCrossRef
9.
go back to reference Gough DB, Donohue JH, Schutt AJ, et al. Pseudomyxoma peritonei. Long-term patient survival with an aggressive regional approach. Ann Surg 1994;219:112–9PubMedCrossRef Gough DB, Donohue JH, Schutt AJ, et al. Pseudomyxoma peritonei. Long-term patient survival with an aggressive regional approach. Ann Surg 1994;219:112–9PubMedCrossRef
10.
go back to reference Shen P, Hawksworth J, Lovato J, et al. Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy with mitomycin C for peritoneal carcinomatosis from nonappendiceal colorectal carcinoma. Ann Surg Oncol 2004;11:178–86PubMedCrossRef Shen P, Hawksworth J, Lovato J, et al. Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy with mitomycin C for peritoneal carcinomatosis from nonappendiceal colorectal carcinoma. Ann Surg Oncol 2004;11:178–86PubMedCrossRef
11.
go back to reference Yan H, Pestieau SR, Shmookler BM, et al. Histopathologic analysis in 46 patients with pseudomyxoma peritonei syndrome: failure versus success with a second-look operation. Mod Pathol 2001;14:164–71PubMedCrossRef Yan H, Pestieau SR, Shmookler BM, et al. Histopathologic analysis in 46 patients with pseudomyxoma peritonei syndrome: failure versus success with a second-look operation. Mod Pathol 2001;14:164–71PubMedCrossRef
12.
go back to reference Semino-Mora C, Doi SQ, Marty A, et al. Intracellular and interstitial expression of H. pylori virulence genes in gastric precancerous intestinal metaplasia and adenocarcinoma. J Infect Dis 2003;187:1165–77PubMedCrossRef Semino-Mora C, Doi SQ, Marty A, et al. Intracellular and interstitial expression of H. pylori virulence genes in gastric precancerous intestinal metaplasia and adenocarcinoma. J Infect Dis 2003;187:1165–77PubMedCrossRef
13.
go back to reference O’Connell JT, Tomlinson JS, Roberts AA, et al. Pseudomyxoma peritonei is a disease of MUC2-expressing goblet cells. Am J Pathol 2002;161:551–64PubMed O’Connell JT, Tomlinson JS, Roberts AA, et al. Pseudomyxoma peritonei is a disease of MUC2-expressing goblet cells. Am J Pathol 2002;161:551–64PubMed
14.
go back to reference O’Connell JT, Hacker CM, Barsky SH. MUC2 is a molecular marker for pseudomyxoma peritonei. Mod Pathol 2002;15:958–72PubMedCrossRef O’Connell JT, Hacker CM, Barsky SH. MUC2 is a molecular marker for pseudomyxoma peritonei. Mod Pathol 2002;15:958–72PubMedCrossRef
15.
go back to reference Li JD, Dohrman AF, Gallup M, et al. Transcriptional activation of mucin by Pseudomonas aeruginosa lipopolysaccharide in the pathogenesis of cystic fibrosis lung disease. Proc Natl Acad Sci USA 1997;94:967–72PubMedCrossRef Li JD, Dohrman AF, Gallup M, et al. Transcriptional activation of mucin by Pseudomonas aeruginosa lipopolysaccharide in the pathogenesis of cystic fibrosis lung disease. Proc Natl Acad Sci USA 1997;94:967–72PubMedCrossRef
16.
go back to reference Dohrman A, Miyata S, Gallup M, et al. Mucin gene (MUC 2 and MUC 5AC) upregulation by Gram-positive and Gram-negative bacteria. Biochim Biophys Acta 1998;1406:251–9PubMed Dohrman A, Miyata S, Gallup M, et al. Mucin gene (MUC 2 and MUC 5AC) upregulation by Gram-positive and Gram-negative bacteria. Biochim Biophys Acta 1998;1406:251–9PubMed
17.
go back to reference Souei-Mhiri M, Tlili-Graies K, Ben CL, et al. Mucocele of the appendix. Retrospective study of 10 cases. J Radiol 2001;82:463–8PubMed Souei-Mhiri M, Tlili-Graies K, Ben CL, et al. Mucocele of the appendix. Retrospective study of 10 cases. J Radiol 2001;82:463–8PubMed
18.
go back to reference Kuroki Y, Otagiri S, Tsukada K. Disseminated peritoneal adenomucinosis associated with a panperitonitis-like onset: report of a case. Surg Today 2001;31:646–50PubMedCrossRef Kuroki Y, Otagiri S, Tsukada K. Disseminated peritoneal adenomucinosis associated with a panperitonitis-like onset: report of a case. Surg Today 2001;31:646–50PubMedCrossRef
19.
go back to reference Ronnett BM, Zahn CM, Kurman RJ, et al. Disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis. A clinicopathologic analysis of 109 cases with emphasis on distinguishing pathologic features, site of origin, prognosis, and relationship to “pseudomyxoma peritonei”. Am J Surg Pathol 1995;19:1390–408PubMedCrossRef Ronnett BM, Zahn CM, Kurman RJ, et al. Disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis. A clinicopathologic analysis of 109 cases with emphasis on distinguishing pathologic features, site of origin, prognosis, and relationship to “pseudomyxoma peritonei”. Am J Surg Pathol 1995;19:1390–408PubMedCrossRef
20.
go back to reference Tummuru MK, Cover TL, Blaser MJ. Cloning and expression of a high-molecular-mass major antigen of Helicobacter pylori: evidence of linkage to cytotoxin production. Infect Immun 1993;61:1799–809PubMed Tummuru MK, Cover TL, Blaser MJ. Cloning and expression of a high-molecular-mass major antigen of Helicobacter pylori: evidence of linkage to cytotoxin production. Infect Immun 1993;61:1799–809PubMed
21.
go back to reference Lan Z-D, Dai L, Zhuo X-L, et al. Gene cloning and sequencing of BmK AS and BmK AS-1, two novel neurotoxins from the scorpion Butus martensi Karsch. Toxicon 1999;37:815–23PubMedCrossRef Lan Z-D, Dai L, Zhuo X-L, et al. Gene cloning and sequencing of BmK AS and BmK AS-1, two novel neurotoxins from the scorpion Butus martensi Karsch. Toxicon 1999;37:815–23PubMedCrossRef
22.
go back to reference Bendayan M, Nanci A, Kan FW. Effect of tissue processing on colloidal gold cytochemistry. J Histochem Cytochem 1987;35:983–96PubMed Bendayan M, Nanci A, Kan FW. Effect of tissue processing on colloidal gold cytochemistry. J Histochem Cytochem 1987;35:983–96PubMed
23.
go back to reference Olivero OA, Chang PK, Lopez-Larraza DM, et al. Preferential formation and decreased removal of cisplatin-DNA adducts in Chinese hamster ovary cell mitochondrial DNA as compared to nuclear DNA. Mutat Res 1997;391:79–86PubMed Olivero OA, Chang PK, Lopez-Larraza DM, et al. Preferential formation and decreased removal of cisplatin-DNA adducts in Chinese hamster ovary cell mitochondrial DNA as compared to nuclear DNA. Mutat Res 1997;391:79–86PubMed
24.
go back to reference Semino-Mora C, Dalakas MC. Rimmed vacuoles with beta-amyloid and ubiquitinated filamentous deposits in the muscles of patients with long-standing denervation (postpoliomyelitis muscular atrophy): similarities with inclusion body myositis. Hum Pathol 1998;29:1128–33PubMedCrossRef Semino-Mora C, Dalakas MC. Rimmed vacuoles with beta-amyloid and ubiquitinated filamentous deposits in the muscles of patients with long-standing denervation (postpoliomyelitis muscular atrophy): similarities with inclusion body myositis. Hum Pathol 1998;29:1128–33PubMedCrossRef
25.
go back to reference Stirling JW, Graff PS. Antigen unmasking for immunoelectron microscopy: labeling is improved by treating with sodium ethoxide or sodium metaperiodate, then heating on retrieval medium. J Histochem Cytochem 1995;43:115–23PubMed Stirling JW, Graff PS. Antigen unmasking for immunoelectron microscopy: labeling is improved by treating with sodium ethoxide or sodium metaperiodate, then heating on retrieval medium. J Histochem Cytochem 1995;43:115–23PubMed
26.
go back to reference Aspholm M, Olfat FO, Norden J, et al. SabA Is the H. pylori hemagglutinin and is polymorphic in binding to sialylated glycans. PLoS Pathog 2006;2:989–1001CrossRef Aspholm M, Olfat FO, Norden J, et al. SabA Is the H. pylori hemagglutinin and is polymorphic in binding to sialylated glycans. PLoS Pathog 2006;2:989–1001CrossRef
27.
go back to reference Necchi V, Candusso ME, Tava F, et al. Intracellular, intercellular and stromal invasion of gastric mucosa, preneoplastic lesions, and cancer by H. pylori. Gastroenterology 2007;132:1009–23PubMedCrossRef Necchi V, Candusso ME, Tava F, et al. Intracellular, intercellular and stromal invasion of gastric mucosa, preneoplastic lesions, and cancer by H. pylori. Gastroenterology 2007;132:1009–23PubMedCrossRef
28.
go back to reference Oliveira AG, Rocha GA, Rocha AM, et al. Isolation of Helicobacter pylori from the intestinal mucosa of patients with Crohn’s disease. Helicobacter 2006;11:2–9PubMedCrossRef Oliveira AG, Rocha GA, Rocha AM, et al. Isolation of Helicobacter pylori from the intestinal mucosa of patients with Crohn’s disease. Helicobacter 2006;11:2–9PubMedCrossRef
29.
go back to reference Thomas JE, Gibson GR, Darboe MK, et al. Isolation of H. pylori from human faeces. Lancet 1992;340:1194–5PubMedCrossRef Thomas JE, Gibson GR, Darboe MK, et al. Isolation of H. pylori from human faeces. Lancet 1992;340:1194–5PubMedCrossRef
30.
go back to reference Luzzi I, Covacci A, Censini S, et al. Detection of a vacuolating cytotoxin in stools from children with diarrhea. Clin Infect Dis 1996;23:101–6PubMed Luzzi I, Covacci A, Censini S, et al. Detection of a vacuolating cytotoxin in stools from children with diarrhea. Clin Infect Dis 1996;23:101–6PubMed
31.
go back to reference Kang W, Rathinavelu S, Samuelson LC, et al. Interferon gamma induction of gastric mucous neck cell hypertrophy. Lab Invest 2005;85:702–15PubMedCrossRef Kang W, Rathinavelu S, Samuelson LC, et al. Interferon gamma induction of gastric mucous neck cell hypertrophy. Lab Invest 2005;85:702–15PubMedCrossRef
32.
go back to reference Dabbagh K, Takeyama K, Lee HM, et al. IL-4 induces mucin gene expression and goblet cell metaplasia in vitro and in vivo. J Immunol 1999;162:6233–7PubMed Dabbagh K, Takeyama K, Lee HM, et al. IL-4 induces mucin gene expression and goblet cell metaplasia in vitro and in vivo. J Immunol 1999;162:6233–7PubMed
33.
go back to reference Kim YD, Kwon EJ, Park DW, et al. Interleukin-1beta induces MUC2 and MUC5AC synthesis through cyclooxygenase-2 in NCI-H292 cells. Mol Pharmacol 2002;62:1112–8PubMedCrossRef Kim YD, Kwon EJ, Park DW, et al. Interleukin-1beta induces MUC2 and MUC5AC synthesis through cyclooxygenase-2 in NCI-H292 cells. Mol Pharmacol 2002;62:1112–8PubMedCrossRef
34.
go back to reference Thompson MA, Ashton RW, Pitot HC. Mucinous appendiceal adenocarcinoma presenting 5 years after appendectomy. Ann Intern Med 2004;140:E677–8 Thompson MA, Ashton RW, Pitot HC. Mucinous appendiceal adenocarcinoma presenting 5 years after appendectomy. Ann Intern Med 2004;140:E677–8
35.
go back to reference Ohara N, Teramoto K. Successful treatment of pseudomyxoma peritonei with intraperitoneal 10 per cent dextrose, sizofiran and cisplatin. J Obstet Gynaecol 2002;22:223PubMedCrossRef Ohara N, Teramoto K. Successful treatment of pseudomyxoma peritonei with intraperitoneal 10 per cent dextrose, sizofiran and cisplatin. J Obstet Gynaecol 2002;22:223PubMedCrossRef
36.
go back to reference Anonymous. IARC Monograph on the evaluation of carcinogenic risks to humans. Schistosomes, liver flukes and Helicobacter pylori. Lyon, France: International Agency for Research on Cancer;1994 Anonymous. IARC Monograph on the evaluation of carcinogenic risks to humans. Schistosomes, liver flukes and Helicobacter pylori. Lyon, France: International Agency for Research on Cancer;1994
37.
go back to reference Itzkowitz SH, Yio X. Inflammation and cancer IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation. Am J Physiol Gastrointest Liver Physiol 2004;287:G7–17PubMedCrossRef Itzkowitz SH, Yio X. Inflammation and cancer IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation. Am J Physiol Gastrointest Liver Physiol 2004;287:G7–17PubMedCrossRef
38.
go back to reference Kucharzik T, Maaser C, Lugering A, et al. Recent understanding of IBD pathogenesis: implications for future therapies. Inflamm Bowel Dis 2006;12:1068–83PubMedCrossRef Kucharzik T, Maaser C, Lugering A, et al. Recent understanding of IBD pathogenesis: implications for future therapies. Inflamm Bowel Dis 2006;12:1068–83PubMedCrossRef
39.
go back to reference Balish E, Warner T. Enterococcus faecalis induces inflammatory bowel disease in interleukin-10 knockout mice. Am J Pathol 2002;160:2253–7PubMed Balish E, Warner T. Enterococcus faecalis induces inflammatory bowel disease in interleukin-10 knockout mice. Am J Pathol 2002;160:2253–7PubMed
40.
go back to reference Wang X, Huycke MM. Extracellular superoxide production by Enterococcus faecalis promotes chromosomal instability in mammalian cells. Gastroenterology 2007;132:551–61PubMedCrossRef Wang X, Huycke MM. Extracellular superoxide production by Enterococcus faecalis promotes chromosomal instability in mammalian cells. Gastroenterology 2007;132:551–61PubMedCrossRef
41.
Metadata
Title
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
Authors
Cristina Semino-Mora
Hui Liu
Thomas McAvoy
Carol Nieroda
Kimberley Studeman
Armando Sardi
Andre Dubois
Publication date
01-05-2008
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 5/2008
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-007-9778-9

Other articles of this Issue 5/2008

Annals of Surgical Oncology 5/2008 Go to the issue