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Signet-ring cell carcinoma of colorectum—current perspectives and molecular biology

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

Colorectal signet-ring cell carcinoma (SRCC) is rare, and very little detailed information on the molecular biology of the disease is available.

Methods

The literature on the clinical, pathological and, in particular, the molecular biology of this rare entity was critically reviewed. The reviewed articles take into account a total of 1,817 cases of SRCC, but only 143 cases have molecular data available. The characteristics of two patients with colorectal SRCC were also discussed.

Results

Colorectal SRCC mostly occurs in younger patients, is larger and has different site predilection compared with conventional colorectal adenocarcinoma. It can occur as one of the synchronous cancers in the colorectum. The cancer is usually diagnosed at advanced stages because of the late manifestation of symptoms, and aggressive treatment strategy is required. Limited reports in the literature have shown that the variant of colorectal cancer demonstrated a different pattern of genetic alterations of common growth kinase-related oncogenes (K-ras, BRAF), tumour suppressor genes (p53, p16), gene methylation and cell adhesion-related genes related to the Wingless signalling pathway (E-cadherin and beta-catenin) from conventional colorectal adenocarcinoma. Colorectal SRCC also showed high expression of mucin-related genes and genes related to the gastrointestinal system. There was also a higher prevalence of microsatellite instability-high tumours and low Cox-2 expression in colorectal SRCC as opposed to conventional adenocarcinoma.

Conclusions

Colorectal SRCC has unique molecular pathological features. The unique molecular profiles in SRCC may provide molecular-based improvements to patient management in colorectal SRCC.

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References

  1. Laufman H, Saphir O (1951) Primary linitis plastica type of carcinoma of the colon. AMA Arch Surg 62:79–91

    CAS  PubMed  Google Scholar 

  2. Anthony T, George R, Rodriguez-Bigas M, Petrelli NJ (1996) Primary signet-ring cell carcinoma of the colon and rectum. Ann Surg Oncol 3:344–348

    Article  CAS  PubMed  Google Scholar 

  3. Messerini L, Palomba A, Zampi G (1995) Primary signet-ring cell carcinoma of the colon and rectum. Dis Colon Rectum 38:1189–1192

    Article  CAS  PubMed  Google Scholar 

  4. Nissan A, Guillem JG, Paty PB, Wong WD, Cohen AM (1999) Signet-ring cell carcinoma of the colon and rectum: a matched control study. Dis Colon Rectum 42:1176–1180

    Article  CAS  PubMed  Google Scholar 

  5. Ooi BS, Ho YH, Eu KW, Seow Choen F (2001) Primary colorectal signet-ring cell carcinoma in Singapore. ANZ J Surg 71:703–706

    Article  CAS  PubMed  Google Scholar 

  6. Kang H, O'Connell JB, Maggard MA, Sack J, Ko CY (2005) A 10-year outcomes evaluation of mucinous and signet-ring cell carcinoma of the colon and rectum. Dis Colon Rectum 48:1161–1168

    Article  PubMed  Google Scholar 

  7. Tung SY, Wu CS, Chen PC (1996) Primary signet ring cell carcinoma of colorectum: an age- and sex-matched controlled study. Am J Gastroenterol 91:2195–2199

    CAS  PubMed  Google Scholar 

  8. Chen JS, Hsieh PS, Hung SY, Tang R, Tsai WS, Changchien CR, Lin PY, Wang JY, Yeh CY (2004) Clinical significance of signet ring cell rectal carcinoma. Int J Colorectal Dis 19:102–107

    Article  PubMed  Google Scholar 

  9. Choi PM, Zelig MP (1994) Similarity of colorectal cancer in Crohn's disease and ulcerative colitis: implications for carcinogenesis and prevention. Gut 35:950–954

    Article  CAS  PubMed  Google Scholar 

  10. Tamai O, Nozato E, Miyazato H, Isa T, Hiroyasu S, Shiraishi M, Kusano T, Muto Y, Higashi M (1999) Radiation-associated rectal cancer: report of four cases. Dig Surg 16:238–243

    Article  CAS  PubMed  Google Scholar 

  11. Fu KI, Sano Y, Kato S, Saito H, Ochiai A, Fujimori T, Saito Y, Matsuda T, Fujii T, Yoshida S (2006) Primary signet-ring cell carcinoma of the colon at early stage: a case report and a review of the literature. World J Gastroenterol 12:3446–3449

    PubMed  Google Scholar 

  12. Siqueira MA, Hayashi T, Yoshinaga K, Saisho S, Utsunomiya J, Sugihara K (2003) Colon cancer in a 14-year-old female with turner syndrome: report of a case. Dis Colon Rectum 46:1560–1562

    Article  PubMed  Google Scholar 

  13. Zenda T, Taniguchi K, Hashimoto T, Takeshita Y, Choto S, Masunaga T, Minato H (2007) Metastatic colon cancer mimicking Crohn's disease. Ann Diagn Pathol 11:427–432

    Article  PubMed  Google Scholar 

  14. Katoh M, Unakami M, Hara M, Fukuchi S (1995) Bone metastasis from colorectal cancer in autopsy cases. J Gastroenterol 30:615–618

    Article  CAS  PubMed  Google Scholar 

  15. Osunkoya AO, Netto GJ, Epstein JI (2007) Colorectal adenocarcinoma involving the prostate: report of 9 cases. Hum Pathol 38:1836–1841

    Article  PubMed  Google Scholar 

  16. Tsai HL, Huang YS, Hsieh JS, Huang TJ, Tsai KB (2002) Signet-ring cell carcinoma of the rectum with diffuse and multiple skin metastases—a case report. Kaohsiung J Med Sci 18:359–362

    PubMed  Google Scholar 

  17. Moonda A, Fatteh S (2009) Metastatic colorectal carcinoma: an unusual presentation. J Cutan Pathol 36:64–66

    Article  PubMed  Google Scholar 

  18. Secco GB, Fardelli R, Campora E, Lapertosa G, Gentile R, Zoli S, Prior C (1994) Primary mucinous adenocarcinomas and signet-ring cell carcinomas of colon and rectum. Oncology 51:30–34

    Article  CAS  PubMed  Google Scholar 

  19. King-Yin Lam A, Ong K, Ho YH (2006) Colorectal mucinous adenocarcinoma: the clinicopathologic features and significance of p16 and p53 expression. Dis Colon Rectum 49:1275–1283

    Article  PubMed  Google Scholar 

  20. Klarskov L, Bernstein I, Holck S (2009) HNPCC-associated synchronous early-stage signet-ring cell carcinomas of colonic origin. A comparative morphological and immunohistochemical study of an intramucosal and a submucosal example. Virchows Arch 454:115–124

    Article  PubMed  Google Scholar 

  21. Sasaki S, Masaki T, Umetani N, Futakawa N, Ando H, Muto T (1998) Characteristics in primary signet-ring cell carcinoma of the colorectum, from clinicopathological observations. Jpn J Clin Oncol 28:202–206

    Article  CAS  PubMed  Google Scholar 

  22. Wistuba II, Behrens C, Albores-Saavedra J, Delgado R, Lopez F, Gazdar AF (2003) Distinct K-ras mutation pattern characterizes signet ring cell colorectal carcinoma. Clin Cancer Res 9:3615–3619

    CAS  PubMed  Google Scholar 

  23. Kawabata Y, Tomita N, Monden T, Ohue M, Ohnishi T, Sasaki M, Sekimoto M, Sakita I, Tamaki Y, Takahashi J, Yagyu T, Mishima H, Kikkawa N, Monden M (1999) Molecular characteristics of poorly differentiated adenocarcinoma and signet-ring-cell carcinoma of colorectum. Int J Cancer 84:33–38

    Article  CAS  PubMed  Google Scholar 

  24. Ogino S, Brahmandam M, Cantor M, Namgyal C, Kawasaki T, Kirkner G, Meyerhardt JA, Loda M, Fuchs CS (2006) Distinct molecular features of colorectal carcinoma with signet ring cell component and colorectal carcinoma with mucinous component. Mod Pathol 19:59–68

    Article  CAS  PubMed  Google Scholar 

  25. Mai KT, Isotalo PA, Guindi M, Burns BF, Parks W (2002) Intestinal epithelial lesions associated with signet ring cell carcinoma of the colon and small intestine. Pathology 34:51–56

    Article  PubMed  Google Scholar 

  26. Park ET, Oh HK, Gum JR Jr, Crawley SC, Kakar S, Engel J, Leow CC, Gao WQ, Kim YS (2006) HATH1 expression in mucinous cancers of the colorectum and related lesions. Clin Cancer Res 12:5403–5410

    Article  CAS  PubMed  Google Scholar 

  27. Park ET, Gum JR, Kakar S, Kwon SW, Deng G, Kim YS (2008) Aberrant expression of SOX2 upregulates MUC5AC gastric foveolar mucin in mucinous cancers of the colorectum and related lesions. Int J Cancer 122:1253–1260

    Article  CAS  PubMed  Google Scholar 

  28. Sentani K, Oue N, Tashiro T, Sakamoto N, Nishisaka T, Fukuhara T, Taniyama K, Matsuura H, Arihiro K, Ochiai A, Yasui W (2008) Immunohistochemical staining of Reg IV and claudin-18 is useful in the diagnosis of gastrointestinal signet ring cell carcinoma. Am J Surg Pathol 32:1182–1189

    Article  PubMed  Google Scholar 

  29. Ogino S, Odze RD, Kawasaki T, Brahmandam M, Kirkner GJ, Laird PW, Loda M, Fuchs CS (2006) Correlation of pathologic features with CpG island methylator phenotype (CIMP) by quantitative DNA methylation analysis in colorectal carcinoma. Am J Surg Pathol 30:1175–1183

    PubMed  Google Scholar 

  30. Darwanto A, Kitazawa R, Maeda S, Kitazawa S (2003) MeCP2 and promoter methylation cooperatively regulate E-cadherin gene expression in colorectal carcinoma. Cancer Sci 94:442–447

    Article  CAS  PubMed  Google Scholar 

  31. Wong SC, Chan AT, Lo ES, Lo YM (2005) Nuclear beta-catenin expression is rare and its potential association with short survival in colorectal signet-ring cell carcinoma. Appl Immunohistochem Mol Morphol 13:248–251

    Article  CAS  PubMed  Google Scholar 

  32. Karnes WE Jr, Shattuck-Brandt R, Burgart LJ, DuBois RN, Tester DJ, Cunningham JM, Kim CY, McDonnell SK, Schaid DJ, Thibodeau SN (1998) Reduced COX-2 protein in colorectal cancer with defective mismatch repair. Cancer Res 58:5473–5477

    CAS  PubMed  Google Scholar 

  33. Lam AK, Ong K, Ho YH (2008) Aurora kinase expression in colorectal adenocarcinoma: correlations with clinicopathological features, p16 expression, and telomerase activity. Hum Pathol 39:599–604

    Article  CAS  PubMed  Google Scholar 

  34. Lam AK, Ong K, Ho YH (2008) hTERT expression in colorectal adenocarcinoma: correlations with p21, p53 expressions and clinicopathological features. Int J Colorectal Dis 23:587–594

    Article  PubMed  Google Scholar 

  35. Shats I, Milyavsky M, Tang X, Stambolsky P, Erez N, Brosh R, Kogan I, Braunstein I, Tzukerman M, Ginsberg D, Rotter V (2004) p53-dependent down-regulation of telomerase is mediated by p21waf1. J Biol Chem 279:50976–50985

    Article  CAS  PubMed  Google Scholar 

  36. Clemo NK, Arhel NJ, Barnes JD, Baker J, Moorghen M, Packham GK, Paraskeva C, Williams AC (2005) The role of the retinoblastoma protein (Rb) in the nuclear localization of BAG-1: implications for colorectal tumour cell survival. Biochem Soc Trans 33:676–678

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Cancer Molecular Pathology Group, School of Medicine, Griffith Health Institute, Gold Coast, QLD, Australia

    Vinod Gopalan, Robert Anthony Smith & Alfred King-Yin Lam

  2. Department of Surgery, School of Medicine, James Cook University, Townsville, QLD, Australia

    Yik-Hong Ho

  3. Griffith Medical School, Griffith University, Gold Coast Campus, Gold Coast, QLD, 4222, Australia

    Alfred King-Yin Lam

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  1. Vinod Gopalan
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  2. Robert Anthony Smith
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  3. Yik-Hong Ho
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  4. Alfred King-Yin Lam
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Correspondence to Alfred King-Yin Lam.

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Gopalan, V., Smith, R.A., Ho, YH. et al. Signet-ring cell carcinoma of colorectum—current perspectives and molecular biology. Int J Colorectal Dis 26, 127–133 (2011). https://doi.org/10.1007/s00384-010-1037-z

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  • DOI: https://doi.org/10.1007/s00384-010-1037-z

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