Association of Cell Signalling Factors with Survival in HNSCC Treated with Chemotherapy or Radiotherapy Plus Cetuximab.
Maria Semidey, Margarita Alberola, Teresa Moline, Isabela Diaz, Jordi Giralt, Sergi Benavente, Santiago Ramon y Cajal. Vall d´Hebron University Hospital, Barcelona, Spain
Background: Head and neck squamous cell carcinomas (HNSCC) have an overall survival rate of 45% over the last three decades. Treatment is based on platinum or radiotherapy and recently, monoclonal antibodies anti EGFR. The aim of this study was to analyze the expression of cell signalling factors in both normal mucosa and tumor and their correlation with relapses or survival in patients treated with combination of cisplatin or radiotherapy with cetuximab.
Design: 41 patients treated with either cisplatin or radiotherapy plus cetuximab were included in this study. Tumors were located in larynx (13), pharynx (5) or mouth (23). Immunohistochemistry for pMAPK, pmTOR, pS6, 4E-BP1, p4EBP1, eIF4E, peIF4E, Ki67 and p16 was performed. Expression levels were semiquantitatively evaluated as percentage and intensity of stained tumor cells and adjacent mucosa [H score]. Statistical analysis was made by means of cross-tabulation by Chi-square and Kruskal-Wallis statistical tests.
Results: In the analysis of cell signalling factors in the adjacent mucosa, an increase of p4E-BP1 (0,05) and eIF4E (0.06) and a low level of pmTOR (0,04) was associated with relapses or dead. Regarding the tumors, high levels of 4E-BP1 (0,01) associated with size of the tumors and high levels of eIF4E (0.05) or peIF4E (0.03) with poorly differentiated carcinomas. A decrease of PTEN expression (0.05), pmTOR (0.05) or low Ki67 (0.03) or p16 (0.005) were associated with relapses or dead. Importantly, the association between low levels of pmTOR or p16 and prognosis was only observed in patients treated with radiotherapy and cisplatin. No other significant correlations were observed in this study.
Conclusions: In the present series of 41 patients with HNSCC, expressions of p4E-BP1, pmTOR and eIF4E in the adjacent mucosa were predictive factors of worse prognosis showing significant correlation with survival. Lack of PTEN expression in tumor cells was the most significant factor associated with relapses or survival. Low levels of pmTOR or p16 protein associate with less response to radiotherapy treatment. Ongoing studies analyze the relevance of cetuximab treatment in these therapeutical regimens to underline the role of cell signalling factors as predictive of response to these new therapeutical approaches.
Category: Head & Neck
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 147, Tuesday Afternoon