Hemminger Jessica A, Toland Amanda Ewart, Scharschmidt Thomas J, Mayerson Joel L, Guttridge Denis C, Iwenofu O Hans
Department of Pathology and Laboratory Medicine, Wexner Medical Center at The Ohio State University, Columbus, OH, USA.
Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Mod Pathol. 2014 Sep;27(9):1238-45. doi: 10.1038/modpathol.2013.244. Epub 2014 Jan 24.
Myxoid and round-cell liposarcoma is a frequently encountered liposarcoma subtype. The mainstay of treatment remains surgical excision with or without chemoradiation. However, treatment options are limited in the setting of metastatic disease. Cancer-testis antigens are immunogenic antigens with the expression largely restricted to testicular germ cells and various malignancies, making them attractive targets for cancer immunotherapy. Gene expression studies have reported the expression of various cancer-testis antigens in liposarcoma, with mRNA expression of CTAG1B, CTAG2, MAGEA9, and PRAME described specifically in myxoid and round-cell liposarcoma. Herein, we further explore the expression of the cancer-testis antigens MAGEA1, ACRBP, PRAME, and SSX2 in myxoid and round-cell liposarcoma by immunohistochemistry in addition to determining mRNA levels of CTAG2 (LAGE-1), PRAME, and MAGEA3 by quantitative real-time PCR. Samples in formalin-fixed paraffin-embedded blocks (n=37) and frozen tissue (n=8) were obtained for immunohistochemistry and quantitative real-time PCR, respectively. Full sections were stained with antibodies to MAGEA1, ACRBP, PRAME, and SSX2 and staining was assessed for intensity (1-2+) and percent tumor positivity. The gene expression levels of CTAG2, PRAME, and MAGEA3 were measured by quantitative real-time PCR. In total, 37/37 (100%) of the samples showed predominantly strong, homogenous immunoreactivity for PRAME. There was a variable, focal expression of MAGEA1 (11%) and SSX2 (16%) and no expression of ACRBP. Quantitative real-time PCR demonstrated PRAME and CTAG2 transcripts in all eight samples: six tumors with high mRNA levels; two tumors with low mRNA levels. The gene expression of MAGEA3 was not detected in the majority of cases. In conclusion, myxoid and round-cell liposarcomas consistently express PRAME by immunohistochemistry as well as CTAG2 and PRAME by qualitative real-time PCR. This supports the use of cancer-testis antigen-targeted immunotherapy in the treatment of this malignancy.
黏液样和圆形细胞脂肪肉瘤是一种常见的脂肪肉瘤亚型。治疗的主要方法仍然是手术切除,可联合或不联合放化疗。然而,对于转移性疾病,治疗选择有限。癌睾丸抗原是具有免疫原性的抗原,其表达主要局限于睾丸生殖细胞和各种恶性肿瘤,这使得它们成为癌症免疫治疗的有吸引力的靶点。基因表达研究报道了脂肪肉瘤中各种癌睾丸抗原的表达,其中CTAG1B、CTAG2、MAGEA9和PRAME的mRNA表达在黏液样和圆形细胞脂肪肉瘤中有具体描述。在此,我们除了通过定量实时PCR测定CTAG2(LAGE-1)、PRAME和MAGEA3的mRNA水平外,还通过免疫组织化学进一步探索癌睾丸抗原MAGEA1、ACRBP、PRAME和SSX2在黏液样和圆形细胞脂肪肉瘤中的表达。分别获取福尔马林固定石蜡包埋块中的样本(n = 37)和冷冻组织样本(n = 8)用于免疫组织化学和定量实时PCR。用抗MAGEA1、ACRBP、PRAME和SSX2的抗体对全切片进行染色,并评估染色强度(1 - 2 +)和肿瘤阳性百分比。通过定量实时PCR测量CTAG2、PRAME和MAGEA3的基因表达水平。总共37/37(100%)的样本对PRAME显示出主要为强的、均匀的免疫反应性。MAGEA1(11%)和SSX2(16%)有可变的、局灶性表达,而ACRBP无表达。定量实时PCR在所有八个样本中均检测到PRAME和CTAG2转录本:六个肿瘤mRNA水平高;两个肿瘤mRNA水平低。大多数病例未检测到MAGEA3的基因表达。总之,黏液样和圆形细胞脂肪肉瘤通过免疫组织化学始终表达PRAME,通过定性实时PCR始终表达CTAG2和PRAME。这支持在这种恶性肿瘤的治疗中使用靶向癌睾丸抗原的免疫疗法。