Mauzo Shakuntala H, Milton Denái R, Prieto Victor G, Torres-Cabala Carlos A, Wang Wei-Lien, Chakravarti Nitin, Nagarajan Priyadharsini, Tetzlaff Michael T, Curry Jonathan L, Ivan Doina, Brown Robert E, Aung Phyu P
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ann Diagn Pathol. 2018 Jun;34:151-154. doi: 10.1016/j.anndiagpath.2018.03.005. Epub 2018 Mar 15.
Serum protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein, which regulates cell proliferation and facilitates intracellular transport of albumin bound particles including chemotherapeutic agents such as Nab-paclitaxel/ABI-007. Therefore the presence of SPARC may achieve higher intra-tumoral drug concentration with lower dosage and thus reduce systemic side-effects. Several trials of ABI-007, in melanoma, show promising clinical activity.
Fifty-four cases of dermal based neoplasms were retrieved including 24 angiosarcomas (AS), 10 hemangiomas, 9 nodular melanomas, 4 Kaposi sarcomas (KS), 3 leiomyosarcomas (LMS), 3 atypical fibroxanthomas (AFX) and 1 spindle cell squamous cell carcinoma (SSCC). SPARC immunohistochemistry (IHC) was performed with a mouse monoclonal antibody.
SPARC expression was detected in a majority of AS (17/24), melanomas (8/9), AFX (3/3), LMS (3/3) and KS (4/4) with some expression in hemangiomas (3/10), while being negative in SSCC (0/1); and was significantly associated with tumor group (p = 0.017). Although a significant difference in overall survival was observed between SPARC expression groups (positive vs. negative) for all patients, there was no significant difference noted among angiosarcoma patients.
We have confirmed the presence of SPARC expression in melanoma, KS, LMS and AS and also detected it for the first time in AFX. Since paclitaxel has shown some effectiveness in AS, melanoma and KS, ABI-007 could also be beneficial in these patients.
富含半胱氨酸的酸性血清蛋白（SPARC）是一种基质细胞糖蛋白，它调节细胞增殖，并促进包括白蛋白结合颗粒（如纳米白蛋白结合型紫杉醇/ABI-007等化疗药物）的细胞内运输。因此，SPARC的存在可能以较低剂量实现更高的肿瘤内药物浓度，从而减少全身副作用。几项关于ABI-007治疗黑色素瘤的试验显示出有前景的临床活性。
检索了54例皮肤源性肿瘤病例，包括24例血管肉瘤（AS）、10例血管瘤、9例结节性黑色素瘤、4例卡波西肉瘤（KS）、3例平滑肌肉瘤（LMS）、3例非典型纤维黄色瘤（AFX）和1例梭形细胞鳞状细胞癌（SSCC）。采用鼠单克隆抗体进行SPARC免疫组织化学（IHC）检测。
在大多数AS（17/24）、黑色素瘤（8/9）、AFX（3/3）、LMS（3/3）和KS（4/4）中检测到SPARC表达，在血管瘤中有一些表达（3/10），而在SSCC中为阴性（0/1）；并且与肿瘤组显著相关（p = 0.017）。尽管所有患者的SPARC表达组（阳性与阴性）之间观察到总生存期有显著差异，但血管肉瘤患者之间没有显著差异。
我们已证实在黑色素瘤、KS、LMS和AS中存在SPARC表达，并且首次在AFX中检测到它。由于紫杉醇在AS、黑色素瘤和KS中已显示出一定疗效，ABI-007对这些患者也可能有益。
