Department of Pathology, University of Pittsburgh, University of Pittsburgh Medical Center Presbyterian/Shadyside Hospitals, Pittsburgh, PA 15232, USA.
Hum Pathol. 2013 May;44(5):725-33. doi: 10.1016/j.humpath.2012.06.023. Epub 2012 Oct 11.
Osteosarcomas rarely occur in older adults. Proteomics has not been reported to date in osteosarcoma occurring in the older adult population. This proteomic investigation was conducted to identify differentially expressed proteins in osteosarcoma occurring in various backgrounds from older adults. Desmoid tumors, known to recur locally but not metastasize, were also analyzed. Protein digests isolated from formalin-fixed, paraffin-embedded tumor tissue specimen representing 14 primary osteosarcomas of soft tissue and bone and 18 desmoid tumors were analyzed by high-resolution liquid chromatography-tandem mass spectrometry for protein identification and relative quantification by spectral counting. Elevated abundance levels of several proteins including heat shock protein 90 (HSP90), elastin microfibril interface-located protein 1, and clusterin were identified in osteosarcoma with slight differences in proteomic profiles. Desmoids had an abundance of collagen II and periostin only. The findings were confirmed by immunohistochemical staining for HSP90 and clusterin in the experimental samples and additionally in 16 posttherapy conventional osteosarcomas in tissue microarrays constructed from heterogeneous sarcomas and benign lesions. All osteosarcomas were positive for HSP90 and clusterin to a variable extent. One case of well-differentiated parosteal osteosarcoma was negative. Thirty of 75 other high-grade sarcomas including cases of chondrosarcoma were positive for HSP90. Low-grade and benign lesions and scars and 18 desmoid tumors had little or no expression of these proteins. HSP90 and clusterin represent candidate markers of aggressiveness in osteosarcoma occurring in older adults and may be indicative of drug resistance.
骨肉瘤在老年人中很少发生。迄今为止，尚无关于老年人骨肉瘤的蛋白质组学报道。本蛋白质组学研究旨在鉴定不同背景下老年人骨肉瘤中差异表达的蛋白质。同时也分析了已知局部复发但不转移的韧带样纤维瘤。从福尔马林固定、石蜡包埋的肿瘤组织标本中分离出的蛋白质消化物，代表了 14 例软组织和骨原发性骨肉瘤和 18 例韧带样纤维瘤，通过高分辨率液相色谱-串联质谱进行蛋白质鉴定，并通过光谱计数进行相对定量。在骨肉瘤中鉴定到几种蛋白质的丰度水平升高，包括热休克蛋白 90（HSP90）、弹性微纤维界面定位蛋白 1 和聚集素，其蛋白质组谱略有差异。韧带样纤维瘤仅富含胶原蛋白 II 和骨膜蛋白。通过实验样本中 HSP90 和聚集素的免疫组织化学染色以及从异质性肉瘤和良性病变构建的组织微阵列中的 16 例常规治疗后骨肉瘤进一步证实了这一发现。所有骨肉瘤在不同程度上均为 HSP90 和聚集素阳性。一例分化良好的骨旁骨肉瘤为阴性。75 例其他高级别肉瘤中的 30 例，包括软骨肉瘤，HSP90 阳性。低级别和良性病变、瘢痕和 18 例韧带样纤维瘤几乎没有或没有这些蛋白质的表达。HSP90 和聚集素是老年人骨肉瘤侵袭性的候选标志物，可能提示耐药性。
