Skip to main content

Advertisement

SpringerLink
Log in

Gender-Related Differences in Pathological and Clinical Tumor Response Based on Immunohistochemical Proteins Expression in Rectal Cancer Patients Treated with Short Course of Preoperative Radiotherapy

  • Original Article
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background

Prognostic value of pretreatment expression of proteins in rectal cancer for early pathological tumor response (pTR), clinical tumor response (CTR) to preoperative radiotherapy (RT), and the potential difference between these parameters depending on patient gender is not established.

Material and Methods

One hundred eleven patients were treated with short preoperative course of RT (SCRT) with 5 Gy dose per fraction during 5 days, followed by surgery 3 to 53 days (mean, 21 days) later. Expression of CD34, Ki-67, GLUT-1, Ku70, BCL-2, and P53 proteins was assessed immunohistochemically.

Results

There were 76 men and 35 women. There were 27, 69, and 15 clinical tumor-node-metastasis (cTNM) tumor stages I, II, and III, respectively. Significant differences in Ki-67, GLUT-1, Ku 70, and BCL-2 expressions between male and female tumors were observed for pathological TNM (pTNM) stage and grade. Association between proteins expression and pTNM, pTR, and CTR was analyzed separately for short (≤15 days) and long (>15 days) break between RT and surgery and males and female patients. For SCRT with short break, no protein was significantly related to pTNM; for pTR, higher Ki-67 and lower BCL-2 expression were correlated with pTR. In the male subgroup, BCL-2 overexpression was predictive. For SCRT with long break, none of the proteins was predictive for pTR, but Ki-67, Ku70 (in female subgroup), and BCL-2 expressions were positively correlated with pTNM. BCL-2 overexpression was associated with CTR in the females only.

Conclusion

In SCRT, long break in the treatment should be avoided because correlation between Ki-67, KU70, and BCL-2 expressions and pTNM after RT might indicate tumor progression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Valentini V, Glimelius B, Haustermans K et al. EURECCA consensus conference highlights about rectal cancer clinical management: the radiation oncologist’s expert review. Radiother Oncol 2013. doi:10.1016/j.radonc.2013.10.024

  2. Pettersson D, Holm T, Iversen H et al. Preoperative short-course radiotherapy with delayed surgery in primary rectal cancer. Br J Surg 2012; 99: 577-583.

    Article  CAS  PubMed  Google Scholar 

  3. Bouzourene H, Bosman FT, Seelentag W et al. Importance of tumor regression assessment in predicting the outcome in patients with locally advanced rectal carcinoma who are treated with preoperative radiotherapy. Cancer 2002; 94: 1121-30.

    Article  PubMed  Google Scholar 

  4. Maas M, Nelemans PJ, Valentini V et al. Long-term outcome in patients with pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol 2010; 11: 835-44.

    Article  PubMed  Google Scholar 

  5. Chetty R, Gill P, Govender D et al. International study on rectal cancer regression grading: interobserver variability with commonly used regression grading systems. Hum Pathol 2012; 43: 1917-23.

    Article  PubMed  Google Scholar 

  6. Church DN, Midgley R, Kerr DJ. Stage II colon cancer. Chin Clin Oncol 2013; 2(2):1-6.

    Google Scholar 

  7. Scott N, Hale A, Deakin M et al. A histological assessment of the response of rectal adenocarcinoma to recombination chemo-radiotherapy: relationship to apoptotic activity, p53 and bcl-3 expression. Europ. J Surg Oncol 1998; 24: 169-73.

    Article  CAS  Google Scholar 

  8. Cascini G L, Avallone A, Delrio P et al. 18F-FDG PET is an early predictor of pathological tumor response to preoperative radiochemotherapy in locally advanced rectal cancer. J Nucl Med 2006; 47: 1241-8.

    CAS  PubMed  Google Scholar 

  9. Gasinska A, Skolyszewski J, Popiela T et al. Bromodeoxyuridine labelling index as an indicator of early tumor response to preoperative radiotherapy in patients with rectal cancer. J Gastrointest Surg 2007; 11: 520-8.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Saigusa S, Toiyama Y, Tanaka K et al. Prognostic significance of glucose transporter-1 (GLUT1) gene expression in rectal cancer after preoperative chemoradiotherapy. Surg Today 2012; 42: 460-9.

    Article  CAS  PubMed  Google Scholar 

  11. Gasinska A, Richter P, Darasz Z et al. Gender-related differences in repopulation and early tumor response to preoperative radiotherapy in rectal cancer patients. J Gastrointest Surg, 15, 1568-76, 2011.

    Article  PubMed  Google Scholar 

  12. Brophy S, Sheehan KM, McNamara DA et al. GLUT-1 expression and response to chemoradiotherapy in rectal cancer. Int J Cancer 2009; 125: 2778-82.

    Article  CAS  PubMed  Google Scholar 

  13. Gerdes J, Lemke H, Baisch H et al. Cell cycle analysis of a proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. I Imunol 1984; 133: 1710-5.

    CAS  Google Scholar 

  14. Komuro Y, Watanabe T, Hosoi Y et al. Prognostic significance of Ku70 protein expression in patients with advanced colorectal cancer. Hepato-Gastroenterol 2005; 52: 995-8.

    Google Scholar 

  15. Krajewsky S, Tanaka S, Takayama S et al. Investigation of subcellular distribution of the bcl-2 oncoprotein: residence in the nuclear envelope, endoplasmic reticulum and outer mitochondrial membrane. Cancer Res 1993; 53: 4701-4.

    Google Scholar 

  16. Manne U, Myers RB, Moron C et al. Prognostic significance of Bcl-2 expression and p53 nuclear accumulation in colorectal adenocarcinoma. Int J Cancer 1997; 74: 346-58.

    Article  CAS  PubMed  Google Scholar 

  17. Levine A. p53, the cellular gatekeeper for growth and division. Cell 1997; 88: 323-31.

    Article  CAS  PubMed  Google Scholar 

  18. Adell G, Sun X-F, Stal O et al. p53 status: an indicator for the effect of preoperative radiotherapy of rectal cancer. Radiother Oncol 1999; 51: 169-174.

    Article  CAS  PubMed  Google Scholar 

  19. World Health Organization. International. International histological classification of tumours. Histological typing of intestinal tumours. Jass JR, Sobin LH (eds). Berlin: Springer, 1989.

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

  21. Therasse P, Arbuck SG, Eisenhauer EA et al. New guidelines to evaluate the response to treatment in solid tumours. J Nat Cancer Inst 2000; 92: 205-16.

    Article  CAS  PubMed  Google Scholar 

  22. Dworak O, Keilholz L, Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorect Dis 1997; 12: 19 - 23.

    Article  CAS  Google Scholar 

  23. Gallego MG, Acenero MJF, Ortega JS et al. Vascular enumeration as a prognosticator for colorectal carcinoma. Europ J Cancer 2000; 36: 55-60.

    Article  Google Scholar 

  24. Rigas B, Borgo S, Elhosseiny A et al. Decreased expression of DNA-dependent protein kinase, a DNA repair protein during human colon carcinogenesis. Cancer Res 2001; 61: 8381-4.

    CAS  PubMed  Google Scholar 

  25. Korabiowska M, Cordon-Cardo C, Schinagi M et al. Loss of KU70/Ku80 expression occurs more frequently in hereditary than in sporadic colorectal tumors. Tissue microarray study. Hum Pathol 2006; 37:448-452.

    Article  CAS  PubMed  Google Scholar 

  26. Jakob Ch, Liersch T, Meyer W et al. Predicive value of Ki67 and p53 in locally advanced rectal cancer: correlation with thymidylate synthase and histopathological tumor regression after neoadjuvant 5-FU-based chemoradiotherapy. World J Gastroenterol 2008; 14: 1060-6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Verstraete M, Debucquoy A, Devos E et al. Hypoxia markers in colorectal cancer. Int J Radiat Biol 2013; 89: 9-15.

    Article  CAS  PubMed  Google Scholar 

  28. Havelund BM, Sorensen FB, Lindebjerg J et al. Pretreatment HIF-1α and GLUT-1 expressions do not correlate with outcome after preoperative chemoradiotherapy in rectal cancer. Anticancer Res 2011; 31: 1559-65.

    CAS  PubMed  Google Scholar 

  29. Marijnen CAM, Kapiteijn E, Nagtegaal ID et al. p53 expression in human rectal tissue after radiotherapy: upregulation in normal mucosa versus functional loss in rectal carcinomas. Int J Radiat Oncol Bio Phys 2002; 52: 720-28.

    Article  CAS  Google Scholar 

  30. Bosari S, Moneghini L, Graziani D et al. Bcl-2 oncoprotein in colorectal hyperplastic polyps, adenomas, and adenocarcinomas. Hum Pathol 1995; 26: 534-40.

    Article  CAS  PubMed  Google Scholar 

  31. Ofner D, Riehemann K, Maier H et al. Immunohistochemically detectable bcl-2 expression in colorectal carcinoma: correlation with tumor stage and patient survival. Brit J Cancer 1995; 72: 981-5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Guzinska-Ustymowicz K, Pryczynicz A, Kemona A et al. Correlation between proliferation markers: PCNA, Ki-67, MCM-2 and antiapoptotic protein Bcl-2 in colorectal cancer. Anticancer Res 2009; 29: 3049-52.

    CAS  PubMed  Google Scholar 

  33. Kikuchi M, Mikami T, Sato T et al. High Ki67, Bax, and thymidylate synthase expression well correlates with response to chemoradiation therapy in locally advanced rectal cancers: proposal of a logistic model for prediction. Brit J Cancer 2009; 101: 116-23.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Anna Cichocka M.Sc. for her valuable assistance. This work was supported by a grant from the State Committee for Scientific Research No: PBZ-KBN-091/P05/2003.

Author information

Authors and Affiliations

  1. Department of Applied Radiobiology, Oncology Center, Maria Sklodowska-Curie Memorial Institute, Garncarska 11, 31-115, Cracow, Poland

    Anna Gasinska, Agnieszka Adamczyk, Joanna Niemiec & Beata Biesaga

  2. Department of Surgery, Oncology Center, Maria Sklodowska-Curie Memorial Institute, Cracow, Poland

    Zbigniew Darasz

  3. Department of Radiation Oncology, Oncology Center, Maria Sklodowska-Curie Memorial Institute, Cracow, Poland

    Jan Skolyszewski

Authors
  1. Anna Gasinska
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Agnieszka Adamczyk
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joanna Niemiec
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Beata Biesaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zbigniew Darasz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jan Skolyszewski
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anna Gasinska.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gasinska, A., Adamczyk, A., Niemiec, J. et al. Gender-Related Differences in Pathological and Clinical Tumor Response Based on Immunohistochemical Proteins Expression in Rectal Cancer Patients Treated with Short Course of Preoperative Radiotherapy. J Gastrointest Surg 18, 1306–1318 (2014). https://doi.org/10.1007/s11605-014-2526-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11605-014-2526-0

Keywords

Search

Navigation