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hTERT expression in colorectal adenocarcinoma: correlations with p21, p53 expressions and clinicopathological features

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Background

The clinicopathological roles and relationships of hTERT, p21 and p53 proteins have not been studied in depth in colorectal cancer. The aim of the present study is to investigate the clinicopathological roles of expression of hTERT protein expression and its relationship with the expression of p21 and p53 proteins in a large cohort of patients with colorectal adenocarcinoma.

Materials and methods

Expressions of hTERT, p21 and p53 proteins were investigated in 188 patients with colorectal adenocarcinomas by immunohistochemistry. The findings were correlated with the clinicopathological features and survival data of colorectal adenocarcinomas.

Results

hTERT, p53 and p21 proteins were detected in 63%, 100% and 62% of the patients with colorectal carcinoma. High level of hTERT protein expression was noted in patients with metastases (p = 0.038) and in patients with rectal cancer (p = 0.046). Loss or low level of p21 protein was often noted in non-mucinous colorectal adenocarcinoma when compared with mucinous adenocarcinoma (p = 0.001). Furthermore, p53 expression was more frequently noted in non-mucinous adenocarcinoma (p = 0.001). The level of expression of p21 protein was positively correlated with expression of level of hTERT protein (p = 0.00001). The survival of the patients was related to staging (p = 0.001) and p53 protein expression (p = 0.038) of the tumours.

Conclusions

hTERT protein expression is an indicator of the biological aggressiveness of the cancer. The level of expression of the protein was also related to the distal location and level of p21 expression of the tumours.

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References

  1. Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991) p53 mutations in human cancers. Science 253:49–53

    Article  PubMed  CAS  Google Scholar 

  2. Shay JW, Bacchetti S (1997) A survey of telomerase activity in human cancer. Eur J Cancer 33:787–791

    Article  PubMed  CAS  Google Scholar 

  3. Shay JW, Wright WE (2007) Hallmarks of telomeres in aging research. J Pathol 211:114–123

    Article  PubMed  CAS  Google Scholar 

  4. Dudkina AS, Lindsley CW (2007) Small molecule protein–protein inhibitors for the p53–MDM2 interaction. Curr Top Med Chem 7:952–960

    Article  PubMed  CAS  Google Scholar 

  5. Alpan RS, Pardee AB (1996) p21WAF1/CIP1/SDI1 is elevated through a p53-independent pathway by mimosine. Cell Growth Differ 7:893–901

    PubMed  CAS  Google Scholar 

  6. Lam KY, Lo CY, Chan KW, Wan KY (2000) Insular and anaplastic carcinoma of the thyroid: A 45-year comparative study at a single institution and a review of the significance of p53 and p21. Ann Surg 231:329–338

    Article  PubMed  CAS  Google Scholar 

  7. Yuen APW, Lam KY, Choy JTH, Ho WK, Wei WI (2000) Clinicopathological significance of p53 and p21 expression in the surgical treatment of laryngeal carcinoma. Anticancer Res 20:4863–4866

    PubMed  CAS  Google Scholar 

  8. Lam KY, Law S, Lo T, Tung HM, Wong J (1999) The clinicopathological significance of p21 and p53 expression in esophageal squamous cell carcinoma: an analysis of 153 patients. Am J Gastroenterol 94:2060–2068

    Article  PubMed  CAS  Google Scholar 

  9. Ng IOL, Lam KY, Ng M, Regezi JA (1999) Expression of p21/waf1 in oral squamous cell carcinomas—correlation with p53 and msdm2 and cellular proliferation index. Oral Oncol 35:63–69

    Article  PubMed  CAS  Google Scholar 

  10. Mabruk MJ, O’Flatharta C (2005) Telomerase: is it the future diagnostic and prognostic tool in human cancer? Expert Rev Mol Diagn 5:907–916

    Article  PubMed  CAS  Google Scholar 

  11. Yan P, Benhattar J, Seelentag W, Stehle JC, Bosman FT (2004) Immunohistochemical localization of hTERT protein in human tissues. Histochem Cell Biol 121:391–397

    Article  PubMed  CAS  Google Scholar 

  12. Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics 2002. CA Cancer J Clin 55:74–108

    Article  PubMed  Google Scholar 

  13. Schwandner O, Bruch HP, Broll R (2002) p21, p27, cyclin D1, and p53 in rectal cancer: immunohistology with prognostic significance? Int J Colorectal Dis 17:11–19

    Article  PubMed  CAS  Google Scholar 

  14. Girlando S, Slomp P, Caffo O, Amichetti M, Togni R, Dvornik G, Tomio L, Galligioni E, Dalla Palma P, Barbareschi M (1999) p21 expression in colorectal carcinomas: a study on 103 cases with analysis of p53 gene mutation/expression and clinic–pathological correlations. Virchows Arch 43:559–565

    Article  Google Scholar 

  15. Malaska J, Kunicka Z, Borsky M, Sklenickova M, Novotna M, Fajkusova L, Zaloudik J, Fajkus J (2004) Telomerase as a diagnostic and predictive marker in colorectal carcinoma. Neoplasma 51:90–96

    PubMed  CAS  Google Scholar 

  16. Saleh S, Lam A, Ho YH (2008) Real-time PCR quantification of human telomerase reverse transcriptase (hTERT) in colorectal cancer. Pathology 40:25–30

    Article  PubMed  CAS  Google Scholar 

  17. Hamilton SR, Vogelstein B, Kudo S et al (2000) Carcinoma of the colon and rectum. In: Hamilton SR, Aaltonen LA (eds) WHO classification of tumours: pathology and genetics of tumours of digestive system. IARC, Lyon, France, pp 105–119

    Google Scholar 

  18. Greene FL, Page DL, Fleming ID, Fritz A, Balch CM, Haller DG, Morrow M (eds) (2002) AJCC cancer staging manual, 6th edn. Springer, New York

    Google Scholar 

  19. 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  PubMed  CAS  Google Scholar 

  20. Ohnishi T, Watanabe T, Nozawa H, Nagawa H (2006) Telomerase subunit immunoreactivity and recurrence in colorectal cancer. Hepatogastroenterology 53:188–191

    PubMed  Google Scholar 

  21. Domont J, Pawlik TM, Boige V, Rose M, Weber JC, Hoff PM, Brown TD, Zorzi D, Morat L, Pignon JP, Rashid A, Jaeck D, Sabatier L, Elias D, Tursz T, Soria JC, Vauthey JN (2005) Catalytic subunit of human telomerase reverse transcriptase is an independent predictor of survival in patients undergoing curative resection of hepatic colorectal metastases: a multicenter analysis. J Clin Oncol 23:3086–3093

    Article  PubMed  CAS  Google Scholar 

  22. Wu YL, Dudognon C, Nguyen E, Hillion J, Pendino F, Tarkanyi I, Aradi J, Lanotte M, Tong JH, Chen GQ, Segal-Bendirdjian E (2006) Immunodetection of human telomerase reverse-transcriptase (hTERT) re-appraised: nucleolin and telomerase cross paths. J Cell Sci 119:2797–2806

    Article  PubMed  CAS  Google Scholar 

  23. Lam AK, 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  Google Scholar 

  24. Lam KY, Lo CY, Wat NMS, Luk JM, Lam KSL (2001) The clinicopathological features and importance of p53, Rb and mdm2 expression in phaeochromocytomas and paragangliomas. J Clin Pathol 54:443–448

    Article  PubMed  CAS  Google Scholar 

  25. Chow V, Yuen APW, Lam KY, Ho WK, Wei WI (2001) Prognostic significance of serum p53 protein and p53 antibody in patients with surgical treatment for head and neck squamous cell carcinoma. Head Neck 23:286–291

    Article  PubMed  CAS  Google Scholar 

  26. Lam KY, Law S, Tung PH, Wong J (2000) Esophageal small cell carcinoma: clinicopathologic parameters, p53 overexpression, proliferative marker, and their impact on pathogenesis. Arch Pathol Lab Med 124:228–233

    PubMed  CAS  Google Scholar 

  27. Lam KY, Law S, Lo T, Tung HM, Wong J (1999) The clinicopathological significance of p21 and p53 expression in esophageal squamous cell carcinoma: an analysis of 153 patients. Am J Gastroenterol 94:2060–2068

    Article  PubMed  CAS  Google Scholar 

  28. Iacopetta B (2002) Are there two sides to colorectal cancer? Int J Cancer 101:403–408

    Article  PubMed  CAS  Google Scholar 

  29. Kapiteijn E, Liefers GJ, Los LC et al (2001) Mechanisms of oncogenesis in colon versus rectal cancer. J Pathol 195:171–178

    Article  PubMed  CAS  Google Scholar 

  30. Birkenkamp-Demtroder K, Olesen SH, Sorensen FB, Laurberg S, Laiho P, Aaltonen LA, Orntoft TF (2005) Differential gene expression in colon cancer of the caecum versus the sigmoid and rectosigmoid. Gut 54:374–384

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The authors would like to thank the staff in Pathology Queensland in providing access to slides and blocks for the study. The project was supported by a grant from the Queensland Cancer Fund.

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Authors and Affiliations

  1. Discipline of Pathology, Griffith Medical School, Griffith University, Gold Coast Campus, Gold Coast, Queensland, 4222, Australia

    Alfred King-Yin Lam

  2. Discipline of Surgery, School of Medicine, James Cook University, Townsville, Queensland, 4811, Australia

    Kate Ong & Yik-Hong Ho

  3. North Queensland Centre for Cancer Research, Australian Institute of Tropical Medicine, James Cook University, Townsville, Queensland, 4811, Australia

    Kate Ong & Yik-Hong Ho

Authors
  1. Alfred King-Yin Lam
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  2. Kate Ong
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  3. Yik-Hong Ho
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Correspondence to Alfred King-Yin Lam.

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Lam, A.KY., Ong, K. & Ho, YH. hTERT expression in colorectal adenocarcinoma: correlations with p21, p53 expressions and clinicopathological features. Int J Colorectal Dis 23, 587–594 (2008). https://doi.org/10.1007/s00384-008-0455-7

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