Leiomyosarcoma and malignant fibrous histiocytoma share similar allelic imbalance pattern at 9p.
Formalin-fixed, paraffin-embedded tissue from 45 soft tissue sarcomas was analysed for allelic imbalance/loss of heterozygosity (AI/LOH) of chromosome 9. The specimens consisted of 17 cases of soft tissue leiomyosarcoma (LMS), 4 cases of cutaneous LMS, 22 cases of conventional malignant fibrous histiocytoma (MFH) and 2 cases of angiomatoid fibrous histiocytoma. All cases were categorised morphologically and immunohistochemically. DNA was microdissected from normal and neoplastic tissues. AI/LOH was performed using six microsatellite markers on the 9p region. The frequency of allelic imbalance at different loci on chromosome 9p was analysed in LMS and MFH and then compared with values previously examined in synovial sarcoma and malignant peripheral nerve sheath tumour. Although AI/LOH and microsatellite instability (MSI) were more frequent in MFH, LMS and MFH groups showed similar patterns of allelic imbalance at the 9p region. Alterations of chromosome 9p have been reported in many cell lines and tumours including LMS and MFH. 9p21 region encodes p16(INK4A) and p15(INK4B). Allelic imbalance observed at 9p 21 in this study suggests that alterations of the negative cell cycle regulators may be an important step in the pathogenesis of MFH and LMS. However, the most frequent allelic imbalance was observed at 9p24 at D9S230. Alterations of this locus were very rare in synovial sarcoma and malignant peripheral nerve sheath tumours and were absent in cutaneous LMS and angiomatoid fibrous histiocytoma. This locus may point to the existence of a genetically altered tumour suppressor gene involved in the pathogenesis of LMS and MFH. Our results support the hypothesis that MFHs may represent a morphological pathway in tumour progression of LMSs.
Sabah
Muna
M
Department of Histopathology, Beaumont Hospital and Royal College of Surgeons in Ireland, Dublin, Ireland. munasabah@eircom.net
Cummins
Robert
R
Leader
Mary
M
Kay
Elaine
E
D022981:Allelic Imbalance; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D018219:Histiocytoma, Benign Fibrous / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007890:Leiomyosarcoma / Q000235:genetics* / Q000473:pathology; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D018317:Nerve Sheath Neoplasms / Q000235:genetics; D016133:Polymerase Chain Reaction; D013584:Sarcoma, Synovial / Q000235:genetics; D012983:Soft Tissue Neoplasms / Q000235:genetics* / Q000473:pathology
D004273:DNA, Neoplasm
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