Microsatellite instability and k-ras, p53 mutations in thyroid lymphoma

Patho-epidemiological studies showed that thyroid lymphoma (TL) arises in i nflammatory lesions of chronic lymphocytic thyroiditis (CLTH), Replication error (RER) is found in inflammatory lesions and associated cancer, suggest ing that chronic inflammation could he a risk factor for neoplastic develop ment through causing RER, To clarify whether RER is involved in the pathoge nesis of TL, we examined the microsatellite instability (MSI) in 9 cases wi th CLTH and 19 with TL, including 10 diffuse large B-cell lymphoma (DLBL), 4 follicle center cell lymphoma, 3 marginal zone B-cell lymphoma of extrano dal (MALT) type, and 2 lymphoplasmacytic type, Sixteen distinct microsatell ite repeats were analyzed, Mutations of p53 and k-ras genes were also exami ned. When alterations at 2 or more microsatellite loci were judged as posit ive, only 5 DLBL cases exhibited MSI, The frequency of MSI in DLBL was sign ificantly higher than that In other types of TL and CLTH (P<0.05), Four of 19 cases (21.1%) showed point mutation of the k-ras gene, The k-ras mutatio ns occurred in the eases with DLBL with RER, and four of five eases with RE R had a k-ras mutation, indicating a close association between RER and k-ra s mutation. p53 mutations were not found in the CLTH Two of 19 TL eases sho wed mutations of p53 gene, There was no significant association between RER and p53 mutation. These findings indicate that genomic instability contrib utes to the progression of TL from low grade to high grade, but not to the development of low grade lymphoma in CLTH lesions.