SUMMARY:Twenty-seven tumor samples with a diagnosis of leiomyosarcomas (LMS) were characterized by comparative genomic hybridization. The results were compared with immunohistochemical analysis of the smooth muscle profile of the tumors and expression of the RB1 gene protein. The comparative genomic hybridization profiles suggested that 7 of the 27 tumors might have been misclassified. High levels of DNA amplification were detected in 20 different small regions and recurrently involved bands 1p34, 1q21, 12q13-15, 17p, and 22q. Most recurrent simple gains were noted at sites such as 1p3, 1q21, 15q12-15, 16p, 17p and 17q, 19, 20q, 22q, and Xp. Significant losses of chromosome 13 were detected in 19 of the 27 tumors with a putative common region of loss in bands 13q14 -21. Losses of chromosomes 1q, 2p and 2q, 4q, 9p, 10p and 10q, 11p and 11q23, and 16q were also highly recurrent. A comparative analysis between the most frequent genomic imbalances observed in this study of LMS and the genomic imbalances observed in a large proportion of malignant fibrous histiocytomas (MFH) from a previous study demonstrated that both types of tumors had similar recurrent imbalances. Although MFH were once thought to be a separate member of the soft tissue sarcoma family, our observations support the hypothesis that MFH are a morphologic modulation in the tumoral progression of other sarcomas, particularly LMS. (Lab Invest 2001, 81:211-215).L eiomyosarcomas (LMS) are relatively frequent sarcomas of adult life. They are principally tumors of uterine or gastrointestinal origin, but also account for 5% to 10% of soft tissue sarcomas (STS) (Enzinger and Weiss, 1995). Within the past few years, with better identification of dedifferentiated liposarcomas and the recognition of malignant fibrous histiocytomas (MFH) as a separate entity, the relative incidence of LMS among STS has changed. The recent characterization of gastrointestinal stromal tumors (GIST) as a distinct classification also influences the incidence of gastrointestinal and retroperitoneal LMS. Contrary to MFH, osteosarcomas, or fibrosarcomas, LMS rarely occur after radiation, but may develop in patients with a constitutional inactivation of one allele of the RB1 gene and with a previous diagnosis of bilateral retinoblastoma. LMS are much more common in women than men, even for nonuterine locations. Until now, few cytogenetic or molecular data were available for LMS (Mandahl et al, 2000), and only a few series were analyzed by comparative genomic hybridization (CGH) (El-Rifai et al, 1998;Otano-Joos et al, 1998;Packenham et al, 1997;Parente et al, 1999). In this study, we analyzed a series of 27 LMS by immunohistochemistry and CGH. We found that the most frequent genomic alterations in LMS were losses in the 13q14 -21 region. LMS and a large proportion of MFH were also found to share very similar CGH imbalance profiles, which suggests that these two tumors may correspond to different differentiation states of a single tumor type.
Results
Imbalances Detected by CGHOne of the ...