Department of Biomedical Sciences and Human Oncology, University of Torino, Torino, Italy.
Mod Pathol. 2011 Nov;24(11):1451-61. doi: 10.1038/modpathol.2011.100. Epub 2011 Jul 15.
Merkel cell carcinoma of the skin is a malignant neuroendocrine tumour, whose prognostic criteria are a matter of dispute. Specifically, no predictor is presently available in stage I-II tumours. We collected clinical and follow-up data from 70 Merkel cell carcinomas of the skin. The same cases were studied for p63 expression by immunohistochemistry, by reverse-transcription PCR (RT-PCR) and TP63 gene status by FISH and for presence of Merkel cell polyomavirus by PCR. Stage emerged as a significant prognostic parameter (P=0.008). p63 expression, detected in 61% (43/70) of cases by immunohistochemistry, was associated with both decreased overall survival (P<0.0001) and disease-free survival (P<0.0001). Variable expression patterns of the different p63 isoforms were found only in cases immunoreactive for p63. In these latter lesions, at least one of the N-terminal p63 isoforms was detected and TAp63α was the most frequently expressed isoform. TP63 gene amplification was observed by FISH in only one case. Presence of Merkel cell polyomavirus DNA sequences was detected in 86% (60/70) of Merkel cell carcinomas and did not emerge as a significant prognostic parameter. Merkel cell carcinoma cases at low stage (stage I-II) represented over half (40/70 cases, 57%) of cases, and the clinical course was uneventful in 25 of 40 cases while 15 cases died of tumour (10/40 cases) within 34 months or were alive with disease (5/40 cases) within 20 months. Interestingly, a very strict correlation was found between evolution and p63 expression (P<0.0001). The present data indicate that p63 expression is associated with a worse prognosis in patients with Merkel cell carcinoma, and in localised tumours it represents the single independent predictor of clinical evolution.
皮肤 Merkel 细胞癌是一种恶性神经内分泌肿瘤，其预后标准存在争议。具体来说，目前在 I-II 期肿瘤中尚无预测指标。我们收集了 70 例皮肤 Merkel 细胞癌的临床和随访数据。通过免疫组织化学、逆转录聚合酶链反应（RT-PCR）和 FISH 研究了相同病例的 p63 表达、TP63 基因状态以及 Merkel 细胞多瘤病毒的存在情况。分期是一个重要的预后参数（P=0.008）。免疫组织化学检测到 61%（43/70）的病例表达 p63，与总生存期（P<0.0001）和无病生存期（P<0.0001）缩短相关。只有在免疫反应性 p63 的病例中才发现不同 p63 同工型的可变表达模式。在这些病变中，检测到至少一种 N 端 p63 同工型，且 TAp63α 是最常表达的同工型。FISH 观察到仅 1 例 TP63 基因扩增。Merkel 细胞多瘤病毒 DNA 序列在 86%（60/70）的 Merkel 细胞癌中被检测到，但不是一个重要的预后参数。低分期（I-II 期）的 Merkel 细胞癌病例占 57%（40/70 例），40 例中有 25 例临床过程无事件，15 例在 34 个月内因肿瘤死亡（40 例中有 10 例），15 例在 20 个月内疾病仍在进展（40 例中有 5 例）。有趣的是，在进化和 p63 表达之间发现了非常严格的相关性（P<0.0001）。本数据表明，p63 表达与 Merkel 细胞癌患者的预后较差相关，在局部肿瘤中，它是临床进展的唯一独立预测因子。
