Divergent patterns of allelic alterations in premalignant laryngeal lesions indicate differences in the impact of morphological grading characteristics.
OBJECTIVE
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.


CONCLUSIONS
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.
Kleist
Britta
B
Institute of Pathology, University of Greifswald, Greifswald, Germany. kliest@uni-greifswald.de
Poetsch
Micaela
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D022981:Allelic Imbalance; D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D002471:Cell Transformation, Neoplastic; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D005260:Female; D006801:Humans; D006965:Hyperplasia; D007818:Laryngeal Diseases / Q000235:genetics / Q000473:pathology; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000473:pathology*; D007830:Larynx / Q000473:pathology*; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D016133:Polymerase Chain Reaction
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; C440408:MIB-1 antibody