Mucinous colorectal adenocarcinoma: influence of mucin expression (Muc1, 2 and 5) on clinico-pathological features and prognosis

  • Rodrigo Oliva Perez
  • Bárbara Helou Bresciani
  • Cláudio Bresciani
  • Igor Proscurshim
  • Desiderio Kiss
  • Joaquim Gama-Rodrigues
  • Diego Daniel Pereira
  • Viviane Rawet
  • Ivan Cecconnello
  • Angelita Habr-Gama
Original Article

Abstract

Background

Mucinous component is associated with distinct clinical and pathological features and poor survival in colorectal cancer. The purpose of this study was to determine differences in outcomes of patients with mucinous colorectal adenocarcinoma according to the type of mucin expressed.

Materials and Methods

Immunohistochemistry was performed in all tumors of patients who underwent radical surgery between 1998 and 2003 with mucinous colorectal cancer using antibodies against MUC1, 2, and 5. Correlation between immunoexpression and clinical, pathological features and survival was performed.

Results

Of the 418 patients treated in this period, only 35 had a mucinous adenocarcinoma. Of these, 25 were positive for 1 or more mucin expression. MUC2 expression correlated with tumor site and depth of penetration, while MUC5 expression correlated to tumor site. Overall survival was significantly worse for patients with MUC2 expression, and disease-free survival was significantly worse for patients with MUC1 expression.

Conclusions

Mucin expression may have significant correlation to specific clinical-pathological features and survival of patients with mucinous-type colorectal adenocarcinoma. These differences may reflect distinct molecular mechanisms involved in carcinogenesis of mucinous colorectal adenocarcinoma.

Keywords

Rectal cancer Mucinous adenocarcinoma Mucins Immunohistochemistry 

References

  1. 1.
    Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ (2005) Cancer statistics. CA Cancer J Clin 55:10–30PubMedGoogle Scholar
  2. 2.
    Greenlee RT, Hill-Harmon MB, Murray T, Thun M (2001) Cancer statistics. CA Cancer J Clin 51:15–36PubMedCrossRefGoogle Scholar
  3. 3.
    Jass JR (1989) Prognostic variables in large bowel cancer. J Clin Pathol 42:1006–1007PubMedCrossRefGoogle Scholar
  4. 4.
    Nelson H, Petrelli N, Carlin A, Couture J, Fleshman J, Guillem J, Miedema B, Ota D, Sargent D (2001) Guidelines 2000 for colon and rectal cancer surgery. J Natl Cancer Inst 93:583–596PubMedCrossRefGoogle Scholar
  5. 5.
    Benson AB 3rd, Schrag D, Somerfield MR, Cohen AM, Figueredo AT, Flynn PJ, Krzyzanowska MK, Maroun J, McAllister P, Van Cutsem E, Brouwers M, Charette M, Haller DG (2004) American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol 22:3408–3419PubMedCrossRefGoogle Scholar
  6. 6.
    Beart RW Jr, Moertel CG, Wieand HS, Leigh JE, Windschitl HE, van Heerden JA, Fitzgibbons RJ Jr, Wolff BG (1990) Adjuvant therapy for resectable colorectal carcinoma with fluorouracil administered by portal vein infusion. A study of the Mayo Clinic and the North Central Cancer Treatment Group. Arch Surg 125:897–901PubMedGoogle Scholar
  7. 7.
    Papadopoulos VN, Michalopoulos A, Netta S, Basdanis G, Paramythiotis D, Zatagias A, Berovalis P, Harlaftis N (2004) Prognostic significance of mucinous component in colorectal carcinoma. Tech Coloproctol 8(Suppl 1):s123–s125PubMedCrossRefGoogle Scholar
  8. 8.
    Glasgow SC, Yu J, Carvalho LP, Shannon WD, Fleshman JW, McLeod HL (2005) Unfavourable expression of pharmacologic markers in mucinous colorectal cancer. Br J Cancer 92:259–264PubMedGoogle Scholar
  9. 9.
    Baldus SE, Zirbes TK, Engel S, Hanisch FG, Monig SP, Lorenzen J, Glossmann J, Fromm S, Thiele J, Pichlmaier H, Dienes HP (1998) Correlation of the immunohistochemical reactivity of mucin peptide cores MUC1 and MUC2 with the histopathological subtype and prognosis of gastric carcinomas. Int J Cancer 79:133–138PubMedCrossRefGoogle Scholar
  10. 10.
    Baldus SE, Monig SP, Hanisch FG, Zirbes TK, Flucke U, Oelert S, Zilkens G, Madejczik B, Thiele J, Schneider PM, Holscher AH, Dienes HP (2002) Comparative evaluation of the prognostic value of MUC1, MUC2, sialyl-Lewis(a) and sialyl-Lewis(x) antigens in colorectal adenocarcinoma. Histopathology 40:440–449PubMedCrossRefGoogle Scholar
  11. 11.
    Hermanek P, Wiebelt H, Staimmer D, Riedl S (1995) Prognostic factors of rectum carcinoma—experience of the German Multicentre Study SGCRC. German Study Group Colo-Rectal Carcinoma. Tumor 81:60–64Google Scholar
  12. 12.
    Du W, Mah JT, Lee J, Sankila R, Sankaranarayanan R, Chia KS (2004) Incidence and survival of mucinous adenocarcinoma of the colorectum: a population-based study from an Asian country. Dis Colon Rectum 47:78–85PubMedCrossRefGoogle Scholar
  13. 13.
    Nozoe T, Anai H, Nasu S, Sugimachi K (2000) Clinicopathological characteristics of mucinous carcinoma of the colon and rectum. J Surg Oncol 75:103–107PubMedCrossRefGoogle Scholar
  14. 14.
    Adell R, Marcote E, Segarra MA, Pellicer V, Gamon R, Bayon AM, Canales M, Torner A (2002) Is mucinous colorectal adenocarcinoma a distinct entity? Gastroenterol Hepatol 25:534–540PubMedGoogle Scholar
  15. 15.
    Okuno M, Ikehara T, Nagayama M, Kato Y, Yui S, Umeyama K (1988) Mucinous colorectal carcinoma: clinical pathology and prognosis. Am Surg 54:681–685PubMedGoogle Scholar
  16. 16.
    Byrd JC, Bresalier RS (2004) Mucins and mucin binding proteins in colorectal cancer. Cancer Metastasis Rev 23:77–99PubMedCrossRefGoogle Scholar
  17. 17.
    Dekker J, Rossen JW, Buller HA, Einerhand AW (2002) The MUC family: an obituary. Trends Biochem Sci 27:126–131PubMedCrossRefGoogle Scholar
  18. 18.
    Nakamori S, Ota DM, Cleary KR, Shirotani K, Irimura T (1994) MUC1 mucin expression as a marker of progression and metastasis of human colorectal carcinoma. Gastroenterology 106:353–361PubMedGoogle Scholar
  19. 19.
    Matsuda K, Masaki T, Watanabe T, Kitayama J, Nagawa H, Muto T, Ajioka Y (2000) Clinical significance of MUC1 and MUC2 mucin and p53 protein expression in colorectal carcinoma. Jpn J Clin Oncol 30:89–94PubMedCrossRefGoogle Scholar
  20. 20.
    Biemer-Huttmann AE, Walsh MD, McGuckin MA, Simms LA, Young J, Leggett BA, Jass JR (2000) Mucin core protein expression in colorectal cancers with high levels of microsatellite instability indicates a novel pathway of morphogenesis. Clin Cancer Res 6:1909–1916PubMedGoogle Scholar
  21. 21.
    Ho SB, Roberton AM, Shekels LL, Lyftogt CT, Niehans GA, Toribara NW (1995) Expression cloning of gastric mucin complementary DNA and localization of mucin gene expression. Gastroenterology 109:735–747PubMedCrossRefGoogle Scholar
  22. 22.
    Byrd JC, Yan P, Sternberg L, Yunker CK, Scheiman JM, Bresalier RS (1997) Aberrant expression of gland-type gastric mucin in the surface epithelium of Helicobacter pylori-infected patients. Gastroenterology 113:455–464PubMedCrossRefGoogle Scholar
  23. 23.
    Biemer-Huttmann AE, Walsh MD, McGuckin MA, Ajioka Y, Watanabe H, Leggett BA, Jass JR (1999) Immunohistochemical staining patterns of MUC1, MUC2, MUC4, and MUC5AC mucins in hyperplastic polyps, serrated adenomas, and traditional adenomas of the colorectum. J Histochem Cytochem 47:1039–1048PubMedGoogle Scholar
  24. 24.
    Kocer B, Soran A, Erdogan S, Karabeyoglu M, Yildirim O, Eroglu A, Bozkurt B, Cengiz O (2002) Expression of MUC5AC in colorectal carcinoma and relationship with prognosis. Pathol Int 52:470–477PubMedCrossRefGoogle Scholar
  25. 25.
    Chang SK, Dohrman AF, Basbaum CB, Ho SB, Tsuda T, Toribara NW, Gum JR, Kim YS (1994) Localization of mucin (MUC2 and MUC3) messenger RNA and peptide expression in human normal intestine and colon cancer. Gastroenterology 107:28–36PubMedGoogle Scholar
  26. 26.
    Weiss AA, Babyatsky MW, Ogata S, Chen A, Itzkowitz SH (1996) Expression of MUC2 and MUC3 mRNA in human normal, malignant, and inflammatory intestinal tissues. J Histochem Cytochem 44:1161–1166PubMedGoogle Scholar
  27. 27.
    Blank M, Klussmann E, Kruger-Krasagakes S, Schmitt-Graff A, Stolte M, Bornhoeft G, Stein H, Xing PX, McKenzie IF, Verstijnen CP et al (1994) Expression of MUC2-mucin in colorectal adenomas and carcinomas of different histological types. Int J Cancer 59:301–306PubMedCrossRefGoogle Scholar
  28. 28.
    Sylvester PA, Myerscough N, Warren BF, Carlstedt I, Corfield AP, Durdey P, Thomas MG (2001) Differential expression of the chromosome 11 mucin genes in colorectal cancer. J Pathol 195:327–335PubMedCrossRefGoogle Scholar
  29. 29.
    Velcich A, Yang W, Heyer J, Fragale A, Nicholas C, Viani S, Kucherlapati R, Lipkin M, Yang K, Augenlicht L (2002) Colorectal cancer in mice genetically deficient in the mucin Muc2. Science 295:1726–1729PubMedCrossRefGoogle Scholar
  30. 30.
    Ookawa K, Kudo T, Aizawa S, Saito H, Tsuchida S (2002) Transcriptional activation of the MUC2 gene by p53. J Biol Chem 277:48270–48275PubMedCrossRefGoogle Scholar
  31. 31.
    Bresalier RS, Niv Y, Byrd JC, Duh QY, Toribara NW, Rockwell RW, Dahiya R, Kim YS (1991) Mucin production by human colonic carcinoma cells correlates with their metastatic potential in animal models of colon cancer metastasis. J Clin Invest 87:1037–1045PubMedCrossRefGoogle Scholar
  32. 32.
    Sternberg LR, Byrd JC, Yunker CK, Dudas S, Hoon VK, Bresalier RS (1999) Liver colonization by human colon cancer cells is reduced by antisense inhibition of MUC2 mucin synthesis. Gastroenterology 116:363–371PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Rodrigo Oliva Perez
    • 1
  • Bárbara Helou Bresciani
    • 1
  • Cláudio Bresciani
    • 1
  • Igor Proscurshim
    • 1
  • Desiderio Kiss
    • 1
  • Joaquim Gama-Rodrigues
    • 1
  • Diego Daniel Pereira
    • 1
  • Viviane Rawet
    • 2
  • Ivan Cecconnello
    • 1
  • Angelita Habr-Gama
    • 1
  1. 1.Department of GastroenterologyUniversity of São Paulo School of MedicineSão PauloBrazil
  2. 2.Department of PathologyUniversity of São Paulo School of MedicineSão PauloBrazil

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