Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
Division of Cellular Signaling Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
Br J Dermatol. 2019 Sep;181(3):535-543. doi: 10.1111/bjd.17789. Epub 2019 Jun 24.
Extramammary Paget disease (EMPD) is a rare intraepithelial adenocarcinoma affecting the genitals and axillary regions. As metastasis of these tumours is itself rare, solid disease management strategies have not been established. Serum carcinoembryonic antigen (CEA) and cytokeratin 19 fragment 21-1 (CYFRA 21-1) levels have been identified as candidate biomarkers for tumour progression in EMPD.
To determine the accuracy of and the correlation between these markers in patients with EMPD.
Serum CEA and CYFRA 21-1 levels were examined in 30 patients with EMPD treated at Keio University Hospital, and compared against clinical information. Both assays were performed at the time of diagnosis, during the postoperative observation period, and following systemic treatment in those with confirmed metastasis. Serum levels were then correlated with tumour progression status and treatment responses.
Normal levels for both assays were observed in all 11 patients with primary localized disease (100%). In patients with metastatic disease the CEA positivity rate was 79% (15 of 19 patients), with a rate of 63% (12 of 19 patients) for CYFRA 21-1. Changes in CEA and CYFRA 21-1 levels were statistically independent; however, using a combined view, elevated levels of either marker improved the positivity rate to 95% (18 of 19 patients). Use of both markers also correlated well with treatment responses.
The combination of CEA and CYFRA 21-1 is useful for predicting metastasis and treatment response in patients with EMPD, especially in those who only have elevation of a single marker. What's already known about this topic? Serum levels of carcinoembryonic antigen (CEA) and cytokine 19 fragment 21-1 (CYFRA 21-1) have been shown to be elevated in patients with extramammary Paget disease (EMPD). Elevation of serum CEA levels is associated with tumour progression of EMPD. A single small study reported that serum CYFRA 21-1 levels are elevated in patients with EMPD with lymph node metastasis. What does this study add? Serum CEA and CYFRA 21-1 were present in 79% and 63% of 19 cases of metastatic EMPD, respectively. Elevations of CEA and CYFRA 21-1 were statistically independent. CEA and CYFRA 21-1 combination assays were positive in 95% of cases of metastatic EMPD. What is the translational message? Combination assays with CEA and CYFRA 21-1 are useful for monitoring treatment response in patients with metastatic EMPD, particularly in those with elevation of either marker.
外阴派杰病（EMPD）是一种罕见的上皮内腺癌，影响生殖器和腋窝区域。由于这些肿瘤的转移本身就很少见，因此尚未建立明确的实体瘤治疗策略。血清癌胚抗原（CEA）和细胞角蛋白 19 片段 21-1（CYFRA 21-1）水平已被确定为 EMPD 肿瘤进展的候选生物标志物。
确定 CEA 和 CYFRA 21-1 这两种标志物在 EMPD 患者中的准确性和相关性。
在庆应义塾大学医院治疗的 30 名 EMPD 患者中检测了血清 CEA 和 CYFRA 21-1 水平，并与临床信息进行了比较。在诊断时、术后观察期间以及在确认转移后对所有患者进行了这两项检测。然后将血清水平与肿瘤进展状况和治疗反应相关联。
11 名原发性局限性疾病患者的两种检测均为正常水平（100%）。转移性疾病患者的 CEA 阳性率为 79%（19 例中的 15 例），CYFRA 21-1 的阳性率为 63%（19 例中的 12 例）。CEA 和 CYFRA 21-1 水平的变化在统计学上是独立的；然而，联合使用这两种标志物可将阳性率提高至 95%（19 例中的 18 例）。两种标志物的联合使用也与治疗反应密切相关。
CEA 和 CYFRA 21-1 的联合使用有助于预测 EMPD 患者的转移和治疗反应，尤其是在仅有一种标志物升高的患者中。
关于这个主题已知的是什么？血清癌胚抗原（CEA）和细胞角蛋白 19 片段 21-1（CYFRA 21-1）的水平已在患有外阴派杰病（EMPD）的患者中升高。CEA 水平升高与 EMPD 的肿瘤进展相关。一项小型研究报告称，CYFRA 21-1 水平在患有 EMPD 淋巴结转移的患者中升高。
这项研究增加了什么？在 19 例转移性 EMPD 中，血清 CEA 和 CYFRA 21-1 分别分别出现在 79%和 63%的病例中。CEA 和 CYFRA 21-1 的升高在统计学上是独立的。CEA 和 CYFRA 21-1 的联合检测在 95%的转移性 EMPD 病例中呈阳性。
这有什么转化意义？CEA 和 CYFRA 21-1 的联合检测可用于监测转移性 EMPD 患者的治疗反应，特别是在有任何一种标志物升高的患者中。
