Bcl-2 expression predicts radiotherapy failure in laryngeal cancer

Abstract

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 (Po0.001) and bcl-X L (P ¼ 0.005) expression and loss of bax expression (P ¼ 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.

Bcl2 and Human Papilloma Virus 16 as Predictors of Outcome following Concurrent Chemoradiation for Advanced Oropharyngeal Cancer

“…Our initial identification of Bcl2 as a biomarker in OPSCC arose from our studies of the cellular mechanisms underlying apoptosis resistance in HNSCC cell lines (13). High levels of Bcl2 expression provide cisplatin resistance to such cell lines (13,28) and the well-known antiapoptotic effects of Bcl2 presumably underlie its association with worse outcome in primary radiotherapy of laryngeal cancer (29). The antiapoptotic mechanisms of Bcl2 and related antiapoptotic proteins are well enough understood that Bcl2 family inhibitors are being evaluated in clinical trials (27).…”

Molecular markers predict outcome in squamous cell carcinoma of the head and neck after concomitant cisplatin‐based chemoradiation

“…BCL-2 has been reported to be predictive for LC in more than half of all published studies. In 4 studies 17,35,36,40 the same cut off value (>5%) was used and a significant association between BCL-2 positivity and LC was observed. Using a cut off value of 30%, a significant association was also seen in 2 other studies.…”

“…Studies describing less than 25 cases, any surgical treatment, esophageal or nasopharyngeal cancer were excluded. Based on these criteria, we selected the following markers: BCL-2, 17,26,[35][36][37][38][39][40] CA9, [18][19][20]41 23 In addition, Cortactin, XPA, MDR1 and TP73 were chosen, because these genes were of interest to the authors.…”

Preadministration of High-Dose Salicylates, Suppressors of NF-κB Activation, May Increase the Chemosensitivity of Many Cancers: An Example of Proapoptotic Signal Modulation Therapy

“…[207][208][209][210] This effect might be mediated by modulation of the expression of members of the bcl-2 family, [211][212][213][214][215][216] whose expression is known to have a major impact on cellular radiosensitivity. [217][218][219][220][221][222] A least a portion of this effect might be secondary to increased production of IGFBP-3, which, through mechanisms that are independent of IGF-I, can boost expression of proapoptotic Bax and Bad while suppressing expression (or activity) of antiapoptotic bcl-2 and bcl-xL in certain cell lines. [227][228][229][230] (The associated local down-regulation of IGF-I activity may also play a role by relieving an inhibitory phosphorylation of Bad.…”