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PRAME 在子宫内膜样癌和浆液性子宫内膜癌中的表达:一个潜在的免疫治疗靶点及可能的诊断陷阱

英文原题:PRAME Expression in Endometrioid and Serous Endometrial Carcinoma: A Potential Immunotherapeutic Target and Possible Diagnostic Pitfall.

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PRAME Expression in Endometrioid and Serous Endometrial Carcinoma: A Potential Immunotherapeutic Target and Possible Diagnostic Pitfall.

PubMed 2022/05/20(内容时间) Int J Gynecol Pathol Q2 · IF 2.1(JCR 2025)

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中文摘要

黑色素瘤优先表达抗原(PRAME)是一种癌睾丸抗原,最初被用作黑色素瘤的诊断标志物。尽管在大多数正常组织中呈阴性,但已有报道其在良性子宫内膜腺体中表达。

此外,PRAME 的表达已在越来越多的实体和血液系统恶性肿瘤中被发现,并且作为预测性生物标志物受到关注,因为针对该分子的癌症疫苗策略和过继性 T 细胞转移正在临床研究中;此外,PRAME 可能有助于筛选适合维A酸治疗的患者。

然而,PRAME 在子宫内膜癌中的表达尚未得到充分研究。我们在此评估 PRAME 在子宫内膜癌中的表达,以更好地描述其作为黑色素瘤诊断标志物的局限性,以及其作为子宫内膜癌预测性生物标志物的潜力。通过组织芯片评估了 256 例子宫内膜样癌(n=235)和浆液性癌(n=21)中 PRAME 的表达。

总体而言,89%(227/256)显示不同程度的核 PRAME 表达,包括 88%(207/235)的子宫内膜样癌和 95%(20/21)的浆液性癌。在所有病例中,70%(179/256)观察到弥漫性(>50%)表达,包括 69%(163/235)的子宫内膜样癌和 76%(16/21)的浆液性癌。表达程度与分级、错配修复蛋白状态或分期之间无关联。PRAME 在子宫内膜癌中的广泛表达提示,在此背景下该标志物不应被解释为黑色素瘤特异性标志物。

然而,PRAME可能作为子宫内膜癌的预测性生物标志物具有实用价值,将基于PRAME的疗法的检测扩展到子宫内膜样癌和浆液性子宫内膜癌,可能为这些子宫内膜癌亚型带来新的治疗选择。

展开英文摘要原文

Preferentially expressed antigen in melanoma (PRAME) is a cancer testes antigen initially employed as a diagnostic marker for melanoma. Although negative in most normal tissues, its expression has been reported in benign endometrial glands.

Additionally, PRAME expression has been identified in a growing list of solid and hematologic malignancies and is of interest as a predictive biomarker, as cancer vaccination strategies and adoptive T-cell transfer targeting this molecule are under clinical investigation; additionally, PRAME may identify candidates for retinoid therapy.

However, expression of PRAME has not been well-studied in endometrial cancers.

We herein evaluate PRAME expression in endometrial carcinomas to better characterize its limitations as a diagnostic melanoma marker as well as its potential as a predictive biomarker in endometrial carcinomas. PRAME expression was evaluated in 256 endometrioid (n=235) and serous (n=21) endometrial carcinomas via tissue microarray. In all, 89% (227/256) demonstrated some degree of nuclear PRAME expression, including 88% (207/235) of endometrioid carcinomas and 95% (20/21) of serous carcinomas.

Diffuse (>50%) expression was observed in 70% (179/256) of all cases, including 69% (163/235) of endometrioid carcinomas and 76% (16/21) of serous carcinomas. There was no association between degree of expression and grade, mismatch repair protein status, or stage. The widespread expression of PRAME in endometrial carcinomas suggests this marker should not be interpreted as specific for melanoma in this context.

However PRAME may have utility as a predictive biomarker in endometrial cancer, and expansion of testing of PRAME-based therapies to endometrioid and serous endometrial carcinomas may lead to new therapeutic options for these endometrial cancer subtypes.

论文信息

作者
Coppock JD、Gradecki SE、Mills AM
第一作者单位
Department of Pathology, University of Virginia, Charlottesville, Virginia.United States
期刊
International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists2023 Jan 1
原文标识
PubMed 35512215 · DOI 10.1097/PGP.0000000000000864