Metastatic Treated Malignant Germ Cell Tumors: Is SALL4 a Better Marker Than Placental Alkaline Phosphatase?
Metastatic Treated Malignant Germ Cell Tumors: Is SALL4 a Better Marker Than Placental Alkaline Phosphatase?
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DOI：
10.1097/pai.0000000000000174
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发表时间：
2016-03
影响因子：
1.6
通讯作者：
N. Andeen;M. Tretiakova
中科院分区：
文献类型：
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作者：
N. Andeen;M. Tretiakova
研究表明，在转移环境和治疗后，免疫组织化学标志物的表达可能减少或丢失。转录因子SALL4（盐样蛋白4）已被认为是原发性和转移性恶性生殖细胞肿瘤（mgct）的敏感标志物，但尚未在治疗后的环境中进行测试。我们试图确定SALL4在治疗耐药转移性MGCT中的表达水平，并与泛gct标志物胎盘碱性磷酸酶（PLAP）进行比较。36例先前治疗过的mgct、16例未经治疗的原发睾丸mgct和4例细胞学标本进行SALL4和PLAP免疫染色，并评估染色特征。在MGCT治疗组中，大多数病例（27/ 36,75 %）存在弥漫性SALL4核免疫反应，标记精原细胞瘤、卵黄囊肿瘤、胚胎癌和原始神经外胚层成分。没有治疗的转移性MGCT缺乏SALL4免疫反应性。相比之下，PLAP仅在14/36 (39%)mgct中弥漫性表达，13/36（36%）显示散在局灶弱至中度阳性，9/36（25%）病例几乎不存在。这两种标记物的分散表达仅限于畸胎瘤区域的上皮成分。SALL4在细胞学块的小样本上也优于PLAP。尽管SALL4不是完全特异性的，但它是一个高度敏感的标志物，在治疗后的大多数mgct中具有很强的弥漫性核反应性，其水平显著高于PLAP （P<0.001）。随着抗SALL4肽的不断开发，SALL4在耐放化疗的转移性mgct中的持续表达也增加了靶向全身治疗的可能性。
Studies have shown that in the metastatic setting and after treatment, expression of immunohistochemical markers may be diminished or lost. Transcription factor SALL4 (sal-like protein 4) has been recognized as a sensitive marker for both primary and metastatic malignant germ cell tumors (MGCTs), but has not been tested in the posttreatment setting. We sought to determine the level of SALL4 expression in treatment-resistant metastatic MGCT in comparison with pan-GCT marker placental alkaline phosphatase (PLAP). Thirty-six previously treated MGCTs, 16 untreated primary testicular MGCTs, and 4 cytology specimens were immunostained for SALL4 and PLAP, and staining characteristics were evaluated. In the treated MGCT group, there was diffuse SALL4 nuclear immunoreactivity in the majority of cases (27/36, 75%), labeling seminoma, yolk-sac tumor, embryonal carcinoma, and primitive neuroectodermal components. No treated metastatic MGCT lacked SALL4 immunoreactivity. In contrast, PLAP was diffusely expressed in only 14/36 (39%) cases of treated MGCTs, showed scattered focal weak to moderate positivity in 13/36 (36%), and was virtually absent in 9/36 (25%) cases. Both markers had scattered expression limited to the epithelial components of teratomatous regions. SALL4 also outperformed PLAP on a small sample of cytology blocks. Although SALL4 is not entirely specific, it is a highly sensitive marker with strong diffuse nuclear reactivity in the majority of MGCTs in the posttreatment setting, at significantly higher levels than PLAP (P<0.001). Persistent expression of SALL4 in metastatic MGCTs resistant to chemoradiation also raises the possibility for targeted systemic therapy as the anti-SALL4 peptide continues to be developed.