title: Loss of heterozygosity on chromosome 6q correlates with decreased thrombospondin-2 expression in human salivary gland carcinomas.
abstract: Since loss of heterozygosity (LOH) on the long arm of chromosome 6q is frequently observed in salivary gland carcinomas, we examined 28 salivary gland carcinomas using 24 microsat- ellite markers mapping to 6q15-27 to identify the commonly deleted region that we felt might contain one or more tumor suppressor genes. LOH was detected in at least one locus in 10 of 28 tumors (35.7%). The most frequently deleted regions occurred between D6S1581 and D6S305 (LOH cluster region 1 (LCR1) and between D6S297 and D6S1590 (LCR2). LOH was observed in 60% of adenoid cystic carcinomas (ACC) and in 57.1% of mucoepidermoid carcinomas (MEC), but was not observed in any locus in any other histological subtypes studied. The gene encoding for thrombospondin-2 (TSP-2) is located in LCR2 and 8 of 9 tumors demonstrating LOH in this region also showed significantly decreased TSP-2 expression by immunohistochemistry. As TSP-2 is a potent inhibitor of tumor growth and angiogenesis, we examined whether TSP-2 expression correlated to microvascular angiogenesis in these tumors and discovered that microvessel counts were significantly higher in lesions with decreased TSP-2 expression (P = 0.02). Our results suggest that 6q LOH may be a significant event in salivary gland carcinogenesis, particularly in ACC and MEC, and that the correlated decrease of TSP-2 expression also plays a critical role.
authors.affiliation: Department of Pathology and Department of Oral and Maxillofacial Surgery, Nara Medical University, Kashihara, Nara 634-8521, Japan.
authors.forename: Munehiro
authors.initials: M
authors.lastname: Kishi
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Nakamura
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Nishimine
authors.forename: Eiwa
authors.initials: E
authors.lastname: Ishida
authors.forename: Keiji
authors.initials: K
authors.lastname: Shimada
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Kirita
authors.forename: Noboru
authors.initials: N
authors.lastname: Konishi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003528:Carcinoma, Adenoid Cystic / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D018277:Carcinoma, Mucoepidermoid / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D002896:Chromosomes, Human, Pair 6; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D012468:Salivary Gland Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D019699:Thrombospondins / Q000235:genetics*; D000099262:Thrombospondin 2
chemical_list: D004273:DNA, Neoplasm; D019699:Thrombospondins; D000099262:Thrombospondin 2