Progression of microsatellite instability from premalignant lesions to tumors of the head and neck.
The role of microsatellite alterations other than loss of heterozygosity (LOH) in the progression of benign epithelium to head-and-neck squamous cell cancer (HNSCC) has not been previously described. As the severity of the dysplasia increases at the microscopic level, there is an increase in the prevalence of LOH as defined by microsatellite analysis. Other alterations have been detected in the form of microsatellite instability (MSI), represented by insertions or deletions of base pairs. It is unknown, however, whether the prevalence of these alterations likewise increases during these early stages of tumor progression. Using 6 selected markers that demonstrate a high rate of MSI and allelic imbalance in invasive head-and-neck cancer, we examined 111 lesions ranging from hyperplasia without atypia to invasive mucosal HNSCC. Two of 34 (5.9%) of the hyperplasias without atypia, 2/12 (16.7%) of the mild dysplasias, 2/21 (9.5%) of the moderate dysplasias, 7/26 (26.9%) of the high-grade dysplasias/carcinomas in situ and 6/18 (33%) of the HNSCCs demonstrated microsatellite base pair length alterations. Our findings indicate that MSI becomes increasingly more common as early dysplastic lesions progress to fully malignant HNSCC and confirm this as a supplemental detection method in microsatellite analysis.
Ha
Patrick K
PK
Head and Neck Cancer Research Division, Department of Otolaryngology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Pilkington
Thomas A
TA
Westra
William H
WH
Sciubba
James
J
Sidransky
David
D
Califano
Joseph A
JA
D020137:Base Pair Mismatch; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D004260:DNA Repair; D018450:Disease Progression; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology