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

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.

• Authors: Herbert Ulrich-Pur, Boban M Erovic, Afschin Soleiman, Barbara Jech, Wolfgang Pennwieser, Cornelia Czembirek, Christoph C Zielinski, Dietmar Thurnher
• Journal: Wiener klinische Wochenschrift (Wien Klin Wochenschr) Vol. 117 Issue 4 Pg. 136-40 (Feb 2005) ISSN: 0043-5325 [Print] Austria
• PMID: 15847193 (Publication Type: Comparative Study, Journal Article)

Chemical References

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

Topics

• Adenocarcinoma (metabolism, radiotherapy)
• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (metabolism)
• Cell Line, Tumor
• Colorectal Neoplasms (metabolism, 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