Lushnikova T, Knuutila S, Miettinen M
Department of Medical Genetics, Haartman Institute and Helsinki University Hospital, University of Helsinki, Finland.
Mod Pathol. 2000 Oct;13(10):1092-6. doi: 10.1038/modpathol.3880203.
Epithelioid sarcoma is a distinctive, rare soft tissue sarcoma that typically involves the distal extremities in young adults, and shows epithelioid morphology and immunohistochemical markers of epithelial differentiation. The genetic background of epithelioid sarcoma is poorly understood, and knowledge of it could give insights into the pathogenesis of this tumor and its possible relationship with other malignant tumors. In this study, we analyzed DNA copy number changes in 30 epithelioid sarcomas by comparative genomic hybridization. DNA was extracted from microdissected samples of formaldehyde-fixed and paraffin-embedded tumors with a minimum of 60% of tumor cells in each sample. Sixteen tumors (53%) showed DNA copy number changes at one to six different genomic sites. The majority of the changes were gains, seen in 14 tumors, whereas 10 tumors showed losses. The most common recurrent gains were at 11q13 (five cases), 1q21-q23 (four cases), 6p21.3 (three cases), and 9q31-qter (three cases). High-level amplifications were detected once in 6p21.3-p21.1 and once in 9q32-qter. Recurrent losses were seen at 9pter-p23 (three cases), 13q22-q32 (three cases), 1p13-p22 (two cases), 3p12-p14 (two cases), 4q13-q33 (two cases), 9p21 (two cases), and 13q32-qter (two cases). The most common recurrent gain at 11q13 was seen in both classic cases and angiomatoid and rhabdoid variants supporting the relationship of these variants with the classic epithelioid sarcoma. Expression of cyclin D1 gene, located in 11q13, was immunohistochemically detected in nine of 15 cases including three of five cases with gain of 11q13, suggesting its involvement in epithelioid sarcoma. The observed comparative genomic hybridization changes give targets for future genetic studies on epithelioid sarcoma.
上皮样肉瘤是一种独特的、罕见的软组织肉瘤，多见于年轻成人的远端肢体，具有上皮样形态及上皮分化的免疫组化标记物。上皮样肉瘤的遗传背景尚不清楚，了解其遗传背景有助于深入了解该肿瘤的发病机制及其与其他恶性肿瘤可能存在的关系。在本研究中，我们通过比较基因组杂交分析了30例上皮样肉瘤的DNA拷贝数变化。DNA取自经显微切割的甲醛固定石蜡包埋肿瘤样本，每个样本中肿瘤细胞最少占60%。16例肿瘤（53%）在1至6个不同基因组位点出现DNA拷贝数变化。大部分变化为扩增，见于14例肿瘤，而10例肿瘤出现缺失。最常见的反复扩增位点为11q13（5例）、1q21 - q23（4例）、6p21.3（3例）和9q31 - qter（3例）。在6p21.3 - p21.1和9q32 - qter各检测到1次高水平扩增。反复缺失见于9pter - p23（3例）、13q22 - q32（3例）、1p13 - p22（2例）、3p12 - p14（2例）、4q13 - q33（2例）、9p21（2例）和13q32 - qter（2例）。经典型病例以及血管瘤样和横纹肌样变型中均可见11q13最常见的反复扩增，这支持了这些变型与经典上皮样肉瘤的关系。位于11q13的细胞周期蛋白D1基因的表达，在15例中的9例通过免疫组化检测到，其中包括5例11q13扩增病例中的3例，提示其与上皮样肉瘤有关。观察到的比较基因组杂交变化为上皮样肉瘤未来的遗传学研究提供了靶点。
