Bcl-2 expression predicts radiotherapy failure in laryngeal cancer.
Early stage laryngeal cancer can be effectively cured by radiotherapy or conservative laryngeal surgery. In the UK, radiotherapy is the preferred first line treatment. However, up to 25% of patients with T2 tumours will demonstrate locally persistent or recurrent disease at the original site, requiring salvage surgery to achieve a definitive cure. Patients experiencing treatment failure have a relatively poor prognosis. A retrospective analysis was conducted consisting of 124 patients with early stage (T1-T2, N0) laryngeal squamous cell carcinoma. In total, 62 patients who failed radiotherapy were matched for T stage, laryngeal subsite and smoking history to a group of 62 patients successfully cured by radiotherapy. Using immunohistochemistry the groups were compared for expression of apoptotic proteins: bcl-2, bcl-X(L), bax, bak and survivin. Radioresistant laryngeal cancer was associated with bcl-2 (P < 0.001) and bcl-X(L) (P = 0.005) expression and loss of bax expression (P = 0.012) in pretreatment biopsies. Bcl-2 has an accuracy of 71% in predicting radiotherapy outcome. The association between expression of bcl-2, bcl-X(L) and bax with radioresistant cancer suggests a potential mechanism by which cancer cells avoid the destructive effects of radiotherapy. Predicting radioresistance, using bcl-2, would allow the clinician to recommend conservative laryngeal surgery as an alternative first line treatment to radiotherapy.
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Postgraduate Medical Institute, University of Hull, Hull York Medical School, Hull, UK.
Cawkwell
L
L
Patmore
H
H
Greenman
J
J
Stafford
N
N
D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000532:radiotherapy* / Q000601:surgery; D005260:Female; D019254:Genes, bcl-2 / Q000502:physiology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007822:Laryngeal Neoplasms / Q000378:metabolism* / Q000532:radiotherapy* / Q000601:surgery; D007825:Laryngectomy; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis; D011237:Predictive Value of Tests; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D011836:Radiation Tolerance / Q000502:physiology*; D012189:Retrospective Studies; D000077022:Survivin; D017211:Treatment Failure
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin