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.
Subject(s)
Adenocarcinoma/metabolism , Adenocarcinoma/radiotherapy , Biomarkers, Tumor/metabolism , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/radiotherapy , Gene Expression Regulation, Neoplastic/radiation effects , Neoplasm Proteins/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Adult , Aged , Aged, 80 and over , Cell Line, Tumor , Female , Humans , Male , Middle Aged , Myeloid Cell Leukemia Sequence 1 Protein , Neoadjuvant Therapy , Prognosis , Radiotherapy, Adjuvant , Retrospective Studies , Statistics as TopicABSTRACT
INTRODUCTION: Malignant gliomas are brain tumors deriving from the brain's glia cells. Primary treatment comprises resection, irradiation and chemotherapy, but these tumors almost always recur. In this situation, palliative chemotherapy is relatively well established, but a second local treatment is sometimes possible. We evaluated the safety and efficacy of re-irradiation in patients with recurrent malignant glioma. PATIENTS AND METHODS: Twenty-two patients were treated with a second irradiation for recurrent or progressive glioma. Patients either received hypo-fractionated stereotactic treatment or conventionally fractionated conformal therapy, depending on tumor size. Wherever possible, a second resection was performed. Time to progression (TTP) and survival were estimated using the Kaplan-Meier product-limit method. RESULTS: Median age was 31 (8-77) years. Median TTP after onset of re-treatment was 4 (1-31) months. Median overall survival was 7 (1-46) months, and overall survival from primary diagnosis was 49 (7-136) months. Significantly longer TTP (P = 0.008) and overall survival (P = 0.005) were observed in re-resected patients than in those without a second surgical intervention. CONCLUSION: Re-irradiation in malignant glioma is a feasible and safe treatment option, and the benefit appears to be especially large in re-resected patients. To make a final conclusion possible, larger prospective trials are warranted.
