Expression of apoptosis-related markers and clinical outcome in patients with advanced colorectal cancer.
The clinical relevance of bax and bcl-2 protein expression has been investigated in 84 patients with recurrent or metastatic colorectal cancer submitted to a chemotherapy regimen including methotrexate and fluorouracil/leucovorin. Cytoplasmic immunostaining of bax and bcl-2 was present in 65.5% and 38%, respectively, of the tumours. No association was found between bax and bcl-2 or between p53 and bax or bcl-2 protein expression. Moreover, the biomarkers were unrelated to patient and tumour characteristics known to affect the clinical outcome of colorectal cancer patients. In general, the apoptosis-related markers did not appear indicative of short- and long-term clinical response nor of prognosis. Bcl-2-negative lesions were more frequent among patients who reached an objective clinical response, which is in agreement with previously reported data regarding other tumour types. When the interrelationship between p53 and bax expression was examined, a better response rate (40%) was found for patients whose tumours did not express p53 and bax, and a better prognosis (2-year probability of overall survival 75%) for patients with p53-positive and bax-negative tumours. In the present series of patients with advanced colorectal cancer submitted to systemic chemotherapy we did not find a clear association between expression of apoptosis-related markers and clinical outcome, even in the subset of patients in which the apoptotic index as determined by the TUNEL approach was investigated.
Clinical Experimental Oncology Laboratory, Oncology Institute, Bari, Italy. anpara@tin.it
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Paradiso
G
G
Simone
M D
MD
Lena
B
B
Leone
C
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Vallejo
J
J
Lacava
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Dellapasqua
M G
MG
Daidone
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Costa
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000276:immunology / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D002955:Leucovorin / Q000627:therapeutic use; D008727:Methotrexate / Q000627:therapeutic use; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D011518:Proto-Oncogene Proteins / Q000276:immunology / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology / Q000378:metabolism; D015996:Survival Rate; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000276:immunology / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D014408:Biomarkers, Tumor; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D002955:Leucovorin; D005472:Fluorouracil; D008727:Methotrexate