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


OBJECTIVE
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.


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.


CONCLUSIONS
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.
Ulrich-Pur
Herbert
H
Department of Internal Medicine I, Vienna University Medical School, Vienna, Austria. herbert.ulrich-pur@meduniwien.ac.at
Erovic
Boban M
BM
Soleiman
Afschin
A
Jech
Barbara
B
Pennwieser
Wolfgang
W
Czembirek
Cornelia
C
Zielinski
Christoph C
CC
Thurnher
Dietmar
D
D000230:Adenocarcinoma / Q000378:metabolism* / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000532:radiotherapy*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D020360:Neoadjuvant Therapy; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D013223:Statistics as Topic
D014408:Biomarkers, Tumor; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2