Changes in Mcl-1 expression in rectal cancer in relation to neo-adjuvant radiotherapy

Wien Klin Wochenschr. 2005 Feb;117(4):136-40. doi: 10.1007/s00508-004-0278-7.

Abstract

Background: Expression of the antiapoptotic protein myeloid cell leukemia-1 (Mcl-1) may be disordered in malignancies of the rectum. High levels of Mcl-1 may correlate with unfavourable clinical outcome.

Aim of the study: The aim of the study was to determine the biologic significance and the prognostic value of the protein Mcl-1 in a group of patients with rectal cancer using immunohistochemical staining in archival specimens.

Patients and methods: Expression of the Bcl-2 family member Mcl-1 was determined in 23 rectal malignancies. Half of the patients with rectal cancer were treated with preoperative short-term radiation therapy of 25 Gy followed by radical surgery; the other patients were treated just with radical surgery. Differences in Mcl-1 expression between irradiated and non-irradiated rectal cancer cells were analysed immunohistochemically, and Mcl-1 expression was correlated with overall survival. Induction of Mcl-1 expression by irradiation versus control in colorectal cancer cells was detected using Western blot.

Results: Mcl-1 was expressed at high levels in 35% of all specimens. Significantly stronger expression was detected in specimens of irradiated rectal cancer compared with non-irradiated tissues (p-value: 0.005). No association was seen between marker expression patterns and clinicopathological data of the respective patients.

Conclusion: Our findings indicate that irradiated rectal cancer produces significantly higher levels of the antiapoptotic protein Mcl-1 than non-irradiated rectal carcinoma. The data also suggest that the high level of Mcl-1 was induced by the radiotherapy. As Mcl-1 is an antiapoptotic regulator, its over-expression in irradiated rectal cancer could constitute a detrimental development antagonizing the potential benefit of adjuvant radiotherapy. Further evaluation of the correlation between Mcl-1 expression and overall survival seems warranted.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / radiotherapy*
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Cell Line, Tumor
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / radiotherapy*
  • Female
  • Gene Expression Regulation, Neoplastic / radiation effects*
  • Humans
  • Male
  • Middle Aged
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoadjuvant Therapy
  • Neoplasm Proteins / metabolism*
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Radiotherapy, Adjuvant
  • Retrospective Studies
  • Statistics as Topic

Substances

  • Biomarkers, Tumor
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-bcl-2