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[癌睾丸(CT)抗原在儿童及青少年黑色素瘤中的表达]

[Expression of cancer testis (CT) antigens in pediatric and adolescent melanomas].

作者信息

Behrendt N, Schultewolter T, Busam K, Frosina D, Spagnoli G, Jungbluth A

机构信息

Department of Surgical Pathology, Roskilde Hospital, Roskilde, Dänemark.

Dermatologische Abteilung, Fachklinik Hornheide, Münster, Deutschland.

出版信息

Pathologe. 2017 Jul;38(4):303-311. doi: 10.1007/s00292-017-0311-z.

DOI:10.1007/s00292-017-0311-z
PMID:28631119
Abstract

BACKGROUND

One of the main problems in the diagnostics of pediatric melanomas is the differentiation from benign dermal lesions typical for this age group, such as Spitz nevus. The biological behavior of pediatric melanomas differs considerably from that of melanomas in adults.

MATERIAL AND METHODS

Cancer testis (CT) antigens are named after their typical expression pattern since they are present in various types of malignant tumors but in normal adult tissues are solely expressed in testicular germ cells. Because of this tumor-associated expression pattern, CT antigens are regarded as potential targets for vaccine-based immunotherapy of cancer and might be used as diagnostic tools in surgical pathology. In adults, melanoma is among the tumors showing a high incidence of CT antigen expression; however, while there is ample knowledge about adult melanomas, little is known about the presence of CT antigens in pediatric melanomas. Consequently, the expression of CT antigens MAGE-A1, MAGE-A4, CT7/MAGE-C1, NY-ESO-1, and GAGE was analyzed in a series of pediatric melanomas. The study was restricted to cases of metastatic disease and/or fatal outcome. A total of 12 cases were available and immunohistochemically analyzed with monoclonal antibodies (mAb).

RESULTS

The expression of CT antigens was generally low and present in only 4 of 12 cases. This is in stark contrast to the expression of these antigens in adult melanomas. Moreover, the extent of expression was very limited with most cases showing only a focal CT antigen expression and only marked in very small tumor areas (<5%).

CONCLUSION

Despite the low case numbers this study indicates that CT antigens are most likely not useful as diagnostic markers in pediatric melanomas or as targets for vaccine-based immunotherapy. It supports the notion that pediatric melanomas show a different biological behavior than their adult counterparts.

摘要

背景

小儿黑色素瘤诊断中的主要问题之一是与该年龄组典型的良性皮肤病变相鉴别,如Spitz痣。小儿黑色素瘤的生物学行为与成人黑色素瘤有很大不同。

材料与方法

癌睾丸(CT)抗原因其典型的表达模式而得名,因为它们存在于各种类型的恶性肿瘤中,但在正常成人组织中仅在睾丸生殖细胞中表达。由于这种肿瘤相关的表达模式,CT抗原被视为基于疫苗的癌症免疫治疗的潜在靶点,并可能用作外科病理学中的诊断工具。在成人中,黑色素瘤是CT抗原表达发生率较高的肿瘤之一;然而,虽然对成人黑色素瘤有充分的了解,但对小儿黑色素瘤中CT抗原的存在知之甚少。因此,对一系列小儿黑色素瘤中CT抗原MAGE-A1、MAGE-A4、CT7/MAGE-C1、NY-ESO-1和GAGE的表达进行了分析。该研究仅限于转移性疾病和/或致命结局的病例。共有12例病例可供使用,并使用单克隆抗体(mAb)进行免疫组织化学分析。

结果

CT抗原的表达普遍较低,12例中仅4例有表达。这与这些抗原在成人黑色素瘤中的表达形成鲜明对比。此外,表达程度非常有限,大多数病例仅显示局灶性CT抗原表达,且仅在非常小的肿瘤区域(<5%)有明显表达。

结论

尽管病例数较少,但本研究表明CT抗原很可能无法作为小儿黑色素瘤的诊断标志物或基于疫苗的免疫治疗靶点。这支持了小儿黑色素瘤与成人黑色素瘤具有不同生物学行为的观点。

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本文引用的文献

1
MAGE-A Antigens and Cancer Immunotherapy.黑色素瘤相关抗原A(MAGE-A)与癌症免疫治疗
Front Med (Lausanne). 2017 Mar 8;4:18. doi: 10.3389/fmed.2017.00018. eCollection 2017.
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MAGE expression in head and neck squamous cell carcinoma primary tumors, lymph node metastases and respective recurrences-implications for immunotherapy.黑色素瘤相关抗原(MAGE)在头颈部鳞状细胞癌原发肿瘤、淋巴结转移灶及各自复发灶中的表达——对免疫治疗的意义
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Lack of XAGE-1b and NY-ESO-1 in metastatic lymph nodes may predict the potential survival of stage III melanoma patients.
转移性淋巴结中缺乏XAGE-1b和NY-ESO-1可能预示着III期黑色素瘤患者的潜在生存期。
J Dermatol. 2017 Jun;44(6):671-680. doi: 10.1111/1346-8138.13730. Epub 2017 Jan 20.
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Cancer-testis antigens PRAME and NY-ESO-1 correlate with tumour grade and poor prognosis in myxoid liposarcoma.癌-睾丸抗原 PRAME 和 NY-ESO-1 与黏液样脂肪肉瘤的肿瘤分级和预后不良相关。
J Pathol Clin Res. 2015 Mar 16;1(3):144-59. doi: 10.1002/cjp2.16. eCollection 2015 Jul.
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MAGE-A is More Highly Expressed Than NY-ESO-1 in a Systematic Immunohistochemical Analysis of 3668 Cases.在对3668例病例的系统性免疫组织化学分析中,黑色素瘤相关抗原A(MAGE-A)的表达水平高于癌胚抗原(NY-ESO-1)。
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Biologic and clinical characteristics of adolescent and young adult cancers: Acute lymphoblastic leukemia, colorectal cancer, breast cancer, melanoma, and sarcoma.青少年和青年癌症的生物学及临床特征:急性淋巴细胞白血病、结直肠癌、乳腺癌、黑色素瘤和肉瘤。
Cancer. 2016 Apr 1;122(7):1017-28. doi: 10.1002/cncr.29871. Epub 2016 Feb 5.
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Pediatric Melanoma and Atypical Melanocytic Neoplasms.儿童黑色素瘤和非典型黑素细胞肿瘤
Cancer Treat Res. 2016;167:331-69. doi: 10.1007/978-3-319-22539-5_15.
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Therapeutic cancer vaccines.治疗性癌症疫苗
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9
Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy.T 淋巴细胞识别的肿瘤抗原:癌症免疫治疗的核心。
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