Chromosomal Instability Predicts the Progression of Premalignant Head and Neck Lesions
Ernst-Jan M Speel, Ewa VE Bergshoeff, Theke JH Siebers, Stijn AJHM Fleskens, Annick Haesevoets, Jeroen AWM van der Laak, Thijs MAW Merkx, Robert P Takes, Pieter J Slootweg, Johannes J Manni, Bernd Kremer. Maastricht University Medical Center, Maastricht, Netherlands; Atrium Medical Center, Heerlen, Netherlands Antilles; St Radboud University Medical Center, Nijmegen, Netherlands
Background: A major dilemma in the management of patients with precursor lesions of the head and neck mucosa lies in deciding which lesions will progress into carcinoma. Currently used treatments are guided by histopathological examination, which however is troubled by inter-observer variability. The aim of this study was to evaluate the value of chromosomal instability (CIN) detected by fluorescence in situ hybridization (FISH) for the identification of head and neck premalignant lesions at risk for progression.
Design: We examined a series of premalignant oral mucosa lesions (n=106 patients) and laryngeal precursor lesions (n=75 patients) by means of FISH on paraffin-embedded tissue sections using chromosome 1 and 7-specific centromere probes. Cell nuclei were analyzed for CIN in the fluorescence microscope, indicated by the presence of chromosome imbalances and/or polyploidization. Results were correlated with histopathological data as well as with collected clinical follow-up data.
Results: In both oral and laryngeal precursor lesions, the 5-year progression-free survival rate was ∼90%. Outcome of routine histopathology did only predict malignant progression when comparing severe dysplasia with lower stage precursor lesions (hyperplasia, mild en moderate dysplasia) (p≤0.038). CIN was detected in all different subgroups of histopathological differentiation. Moreover, the percentage of precursor lesions harboring CIN increased with progressing histopathological stage. CIN was significantly associated with a lower progression-free survival as compared with lesions without CIN (p<0.001).
Conclusions: The tumorigenesis of the head and neck mucosa is associated with the development of CIN, which can reliably identify lesions at risk for malignant progression. Therefore, intensive follow-up and/or a more aggressive treatment of lesions with CIN should be considered, and for example examined in prospective studies.
Category: Head & Neck
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 164, Wednesday Morning