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.