Divergent Patterns of Allelic Alterations in Premalignant Laryngeal Lesions Indicate Differences in the Impact of Morphological Grading Characteristics

Abstract

Objectives: Classic histological grading and molecular genetic analysis of epithelial hyperplastic laryngeal lesions (EHLL) were correlated in an attempt to elucidate, which classic marker reflects best the gradual progression of laryngeal premalignant lesions as determined by an increasing number of molecular genetic aberrations. Methods: Thirty-two EHLL were grouped according to four grades of nuclear atypia, four degrees of epithelial maturation and three groups of overall and suprabasal mitotic activity. Overall and suprabasal proliferative activity were measured by MIB-1 immunostaining and staged according to four levels. Allelic imbalance was determined by PCR using 32 microsatellite loci at nine chromosomal arms. Results: Of the six classic criteria, only progressive mitotic indices correlated with allelic alterations in a remarkable variety of microsatellite markers, especially at chromosome 17p. Conclusion: Using the number of allelic alterations as standard for assessment, this preliminary study gives first evidence that certain morphological criteria could reflect differently the gradual progression of premalignant laryngeal lesions with mitotic index being the most promising marker. Further studies with long-term follow-up are required to prove the predictive value of these criteria in daily practice.

The clinical relevance of microsatellite alterations in head and neck squamous cell carcinoma: a critical review

“…The modern automatic fragment analysis procedures offer high throughput analysis and a more precise and quantitative 60 -64 Although other points of discussion are the cutoff values to be used for LOH ratios (the ratio between the peak height ratios of both alleles of normal and paired tumor sample), 9,39,63,65 there is fairly general agreement that appropriate cutoffs are 42 or o0.5. A last issue is on the different types of MSI.…”

“…17,18,19,33 There are several reports that LOH is associated with more advanced stage and more aggressive HNSCC tumors, 13,34,36,37,56 and specifically with nodal involvement. 32,44 Other authors describe very specific correlations such as a link between LOH at 17p and mitotic index, 39 a connection of LOH at MLH1 with lower grade HNSCC, and LOH at CDKN2A with higher grade, 9 or a preference of LOH in tumors originating from the pharynx. 56 A correlation between LOH and other patient-related factors like age and race, was described in some studies.…”

Current review on squamous intraepithelial lesions of the larynx

“…Many researchers have provided meticulous analyses of histological classifications of SILs in relation to their biological behaviour 2–4,6–27 . These analyses have been recently further supplemented by molecular genetic investigations trying to elucidate the pathogenic mechanisms of SCC development, and to improve the prognostic evaluation of SILs 1,28–51 …”