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Proliferating Cell Nuclear Antigen as a Prognostic Factor After Total Mesorectal Excision of Stage II–III Rectal Cancer

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

Abstract

Background

Proliferating cell nuclear antigen (PCNA) is an auxiliary protein of DNA polymerase delta that is tightly associated with sites of DNA replication; whether PCNA is a definite prognostic factor remains controversial. This study determined the clinicopathological factors associated with the long-term oncological outcome after radical resection of stage II–III rectal cancer, focusing on PCNA.

Methods

We retrospectively reviewed 135 consecutive patients who underwent curative surgery for stage II–III rectal cancer between August 2001 and April 2004. Prognostic factors including immunohistochemical PCNA expression and the clinical outcome were evaluated.

Results

The PCNA index correlated with lymph node metastasis (= 0.010). A multivariate analysis identified two independent factors that significantly affected both disease-free and overall survival: lymph node metastasis and PCNA index. With a median follow-up period of 60 months (range 8–87 months), both 5-year disease-free and overall survival of the low PCNA group were significantly higher than those of the high PCNA group (71.8% versus 32.0%, < 0.001; 83.9% versus 50.0%, < 0.001, respectively).

Conclusion

For patients undergoing curative resection for rectal cancer, pathological N stage and high PCNA expression can provide valuable prognostic information about survival. This study suggests that the PCNA index may be used as an independent prognostic factor in stage II–III rectal cancer patients.

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References

  1. Peeters KC, Marijnen CA, Nagtegaal ID, et al. The TME trial after a median follow-up of 6 years: increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma. Ann Surg. 2007;246:693–701.

    Article  PubMed  Google Scholar 

  2. den Dulk M, Krijnen P, Marijnen CA, et al. Improved overall survival for patients with rectal cancer since 1990: the effects of TME surgery and pre-operative radiotherapy. Eur J Cancer. 2008;44:1710–6.

    Article  Google Scholar 

  3. Swedish Rectal Cancer Trial. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med. 1997;336:980–7.

    Article  Google Scholar 

  4. Heald RJ, Ryall RD. Recurrence and survival after total mesorectal excision for rectal cancer. Lancet. 1986;1:1479–82.

    Article  PubMed  CAS  Google Scholar 

  5. Guzinska-Ustymowicz K, Stepien E, Kemona A. MCM-2, Ki-67 and PCNA protein expressions in pT3G2 colorectal cancer indicated lymph node involvement. Anticancer Res. 2008;28:451–7.

    PubMed  Google Scholar 

  6. Nakae S, Nakamura T, Ikegawa R, Yoshioka H, Shirono J, Tabuchi Y. Evaluation of argyrophilic nucleolar organizer region and proliferating cell nuclear antigen in colorectal cancer. J Surg Oncol. 1998;69:28–35.

    Article  PubMed  CAS  Google Scholar 

  7. Paradiso A, Rabinovich M, Vallejo C, et al. p53 and PCNA expression in advanced colorectal cancer: response to chemotherapy and long-term prognosis. Int J Cancer. 1996;69:437–41.

    Article  PubMed  CAS  Google Scholar 

  8. al-Sheneber IF, Shibata HR, Sampalis J, Jothy S. Prognostic significance of proliferating cell nuclear antigen expression in colorectal cancer. Cancer. 1993;71:1954–9.

    Article  PubMed  CAS  Google Scholar 

  9. Sun XF, Carstensen JM, Stal O, Zhang H, Nordenskjold B. Proliferating cell nuclear antigen (PCNA) in relation to ras, c-erbB-2,p53, clinico-pathological variables and prognosis in colorectal adenocarcinoma. Int J Cancer. 1996;69:5–8.

    Article  PubMed  CAS  Google Scholar 

  10. Neoptolemos JP, Oates GD, Newbold KM, Robson AM, McConkey C, Powell J. Cyclin/proliferation cell nuclear antigen immunohistochemistry does not improve the prognostic power of Dukes’ or Jass’ classifications for colorectal cancer. Br J Surg. 1995;82:184–7.

    Article  PubMed  CAS  Google Scholar 

  11. Reed JA, Manahan LJ, Park CS, Brigati DJ. Complete one-hour immunocytochemistry based on capillary action. Biotechniques. 1992;13:434–43.

    PubMed  CAS  Google Scholar 

  12. Yang HB, Hsu PI, Chan SH, Lee JC, Shin JS, Chow NH. Growth kinetics of colorectal adenoma-carcinoma sequence: an immunohistochemical study of proliferating cell nuclear antigen expression. Hum Pathol. 1996;27:1071–6.

    Article  PubMed  CAS  Google Scholar 

  13. Kelman Z. PCNA: structure, functions and interactions. Oncogene. 1997;14:629–40.

    Article  PubMed  CAS  Google Scholar 

  14. Jin W, Gao MQ, Lin ZW, Yang DX. Multiple biomarkers of colorectal tumor in a differential diagnosis model: a quantitative study. World J Gastroenterol. 2004;10:439–42.

    PubMed  Google Scholar 

  15. Wu J, Mao Y, He L, et al. A new cell proliferating marker: cytosolic thymidine kinase as compared to proliferating cell nuclear antigen in patients with colorectal carcinoma. Anticancer Res. 2000;20:4815–20.

    PubMed  CAS  Google Scholar 

  16. Lavezzi AM, Ottaviani G, De Ruberto F, Fichera G, Matturri L. Prognostic significance of different biomarkers (DNA content, PCNA, karyotype) in colorectal adenomas. Anticancer Res. 2002;22:2077–81.

    PubMed  Google Scholar 

  17. Choi HJ, Jung IK, Kim SS, Hong SH. Proliferating cell nuclear antigen expression and its relationship to malignancy potential in invasive colorectal carcinomas. Dis Colon Rectum. 1997;40:51–9.

    Article  PubMed  CAS  Google Scholar 

  18. Shimada N, Suzuki J, Fujita J, et al. A comparative study of nucleolar organizer region, proliferating cell nuclear antigen and epidermal growth factor receptor staining in colon tumours. J Gastroenterol Hepatol. 1998;13:794–800.

    Article  PubMed  CAS  Google Scholar 

  19. Teixeira CR, Tanaka S, Haruma K, Yoshihara M, Sumii K, Kajiyama G. Proliferating cell nuclear antigen expression at the invasive tumor margin predicts malignant potential of colorectal carcinomas. Cancer. 1994;73:575–9.

    Article  PubMed  CAS  Google Scholar 

  20. Peng JJ, Cai SJ, Lu HF, et al. Predicting prognosis of rectal cancer patients with total mesorectal excision using molecular markers. World J Gastroenterol. 2007;13:3009–15.

    PubMed  Google Scholar 

  21. Qiu H, Sirivongs P, Rothenberger M, Rothenberger DA, Garcia-Aguilar J. Molecular prognostic factors in rectal cancer treated by radiation and surgery. Dis Colon Rectum. 2000;43:451–9.

    Article  PubMed  CAS  Google Scholar 

  22. Peng J, Xu Y, Guan Z, et al. Prognostic significance of the metastatic lymph node ratio in node-positive rectal cancer. Ann Surg Oncol. 2008;15:3118–23.

    Article  PubMed  Google Scholar 

  23. Kim NK, Baik SH, Seong JS, et al. Oncologic outcomes after neoadjuvant chemoradiation followed by curative resection with tumor-specific mesorectal excision for fixed locally advanced rectal cancer: Impact of postirradiated pathologic downstaging on local recurrence and survival. Ann Surg. 2006;244:1024–30.

    Article  PubMed  Google Scholar 

  24. Onaitis MW, Noone RB, Hartwig M, et al. Neoadjuvant chemoradiation for rectal cancer: analysis of clinical outcomes from a 13-year institutional experience. Ann Surg. 2001;233:778–85.

    Article  PubMed  CAS  Google Scholar 

  25. Huh JW, Jung EJ, Park YA, Lee KY, Sohn SK. Sphincter-preserving operations following preoperative chemoradiation: an alternative to abdominoperineal resection for lower rectal cancer? World J Surg. 2008;32:1116–23.

    Article  PubMed  Google Scholar 

  26. Leo E, Belli F, Miceli R, et al. Distal clearance margin of 1 cm or less: a safe distance in lower rectum cancer surgery. Int J Colorectal Dis. 2009;24:317–22.

    Article  PubMed  Google Scholar 

  27. Kuvshinoff B, Maghfoor I, Miedema B, et al. Distal margin requirements after preoperative chemoradiotherapy for distal rectal carcinomas: are < or = 1 cm distal margins sufficient? Ann Surg Oncol. 2001;8:163–9.

    PubMed  CAS  Google Scholar 

  28. Marijnen CA, Nagtegaal ID, Kapiteijin E, et al. Radiotherapy dose not compensate for positive resection margin in rectal cancer patients: report of a multicenter randomized trial. Int J Radiat Oncol Biol Phys. 2003;55:1311–20.

    PubMed  CAS  Google Scholar 

  29. Baik SH, Kim NK, Lee YC, et al. Prognostic significance of circumferential resection margin following total mesorectal excision and adjuvant chemoradiotherapy in patients with rectal cancer. Ann Surg Oncol. 2007;14:462–9.

    Article  PubMed  Google Scholar 

  30. Park IJ, Kim HC, Yu CS, et al. Effect of adjuvant radiotherapy on local recurrence in stage II rectal cancer. Ann Surg Oncol. 2008;15:519–25.

    Article  PubMed  Google Scholar 

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Acknowledgment

This work was supported by a Research Grant (0720570) from the National Cancer Center of South Korea.

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Correspondence to Hyeong Rok Kim MD.

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Huh, J.W., Kim, H.R. & Kim, Y.J. Proliferating Cell Nuclear Antigen as a Prognostic Factor After Total Mesorectal Excision of Stage II–III Rectal Cancer. Ann Surg Oncol 16, 1494–1500 (2009). https://doi.org/10.1245/s10434-009-0424-6

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  • DOI: https://doi.org/10.1245/s10434-009-0424-6

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