Department of Ophthalmology, University of Cincinnati College of Medicine, 260 Stetson Street, Suite 5300, Cincinnati, OH, 45267, USA,
Graefes Arch Clin Exp Ophthalmol. 2014 Jan;252(1):131-5. doi: 10.1007/s00417-013-2515-0. Epub 2013 Nov 24.
To determine the relative sufficiency of paired aspirates of posterior uveal melanomas obtained by FNAB for cytopathology and GEP, and their prognostic significance for predicting death from metastasis.
Prospective non-randomized IRB-approved single-center longitudinal clinical study of 159 patients with posterior uveal melanoma sampled by FNAB in at least two tumor sites between 09/2007 and 12/2010. Cases were analyzed with regard to sufficiency of the obtained aspirates for cytopathologic classification and GEP classification. Statistical strength of associations between variables and GEP class was computed using Chi-square test. Cumulative actuarial survival curves of subgroups of these patients based on their cytopathologic versus GEP-assigned categories were computed by the Kaplan-Meier method. The endpoint for this survival analysis was death from metastatic uveal melanoma.
FNAB aspirates were insufficient for cytopathologic classification in 34 of 159 cases (21.9 %). In contrast, FNAB aspirates were insufficient for GEP classification in only one of 159 cases (0.6 %). This difference is statistically significant (P < 0.001). Six of 34 tumors (17.6 %) that yielded an insufficient aspirate for cytopathologic diagnosis were categorized as GEP class 2, while 43 of 125 tumors (34.7 %) that yielded a sufficient aspirate for cytopathologic diagnosis were categorized as GEP class 2. To date, 14 of the 49 patients with a GEP class 2 tumor (28.6 %) but only five of the 109 patients with a GEP class 1 tumor (5.6 %) have developed metastasis. Fifteen of 125 patients (12 %) whose tumors yielded sufficient aspirates for cytopathologic classification but only four of 34 patients (11.8 %) whose tumors yielded insufficient aspirates for cytopathologic classification developed metastasis. The median post-biopsy follow-up time for surviving patients in this series was 32.5 months. Cumulative actuarial 5-year probability of death from metastasis 14.1 % for those with an insufficient aspirate for cytopathologic classification versus 22.4 % for those with a sufficient aspirate for cytopathologic classification (log rank P = 0.68). In contrast, the cumulative actuarial 5-year probability of metastatic death was 8.0 % for those with an insufficient/unsatisfactory aspirate for GEP classification or GEP class 1 tumor, versus 45.0 % for those with a GEP class 2 tumor (log rank P = 0.005).
This study confirmed that GEP classification of posterior uveal melanoma cells obtained by FNAB is feasible in almost all cases, including most in which FNAB yields an insufficient aspirate for cytodiagnosis. The study also confirmed that GEP classification is substantially better than cytologic classification for predicting subsequent metastasis and metastatic death.
确定通过细针抽吸活检(FNAB)获得的后葡萄膜黑色素瘤配对抽吸物在细胞病理学和基因表达谱(GEP)分析方面的相对充分性,及其对预测转移性死亡的预后意义。
这是一项前瞻性、非随机、经机构审查委员会批准的单中心纵向临床研究,纳入了 2007 年 9 月至 2010 年 12 月期间至少在两个肿瘤部位通过 FNAB 取样的 159 例后葡萄膜黑色素瘤患者。对获得的抽吸物进行细胞病理学分类和 GEP 分类的充分性进行分析。使用卡方检验计算变量与 GEP 分类之间关联的统计强度。根据细胞病理学与 GEP 分类的亚组,使用 Kaplan-Meier 方法计算这些患者的累积生存曲线。该生存分析的终点是转移性葡萄膜黑色素瘤导致的死亡。
在 159 例病例中,有 34 例(21.9%)FNAB 抽吸物不足以进行细胞病理学分类。相比之下,仅有 1 例(0.6%)159 例病例的 FNAB 抽吸物不足以进行 GEP 分类。这一差异具有统计学意义(P<0.001)。在 34 例细胞病理学诊断不充分的肿瘤中,有 6 例(17.6%)被归类为 GEP 类 2,而在 125 例细胞病理学诊断充分的肿瘤中,有 43 例(34.7%)被归类为 GEP 类 2。迄今为止,在 49 例 GEP 类 2 肿瘤患者中,有 14 例(28.6%)发生了转移,而在 109 例 GEP 类 1 肿瘤患者中,仅有 5 例(5.6%)发生了转移。在 125 例细胞病理学分类充分的患者中,有 15 例(12%)发生了转移,而在 34 例细胞病理学分类不充分的患者中,仅有 4 例(11.8%)发生了转移。在本研究系列中,存活患者的中位活检后随访时间为 32.5 个月。对于细胞病理学分类抽吸物不充分的患者,累积 5 年转移性死亡的概率为 14.1%,而对于细胞病理学分类抽吸物充分的患者,这一概率为 22.4%(对数秩检验,P=0.68)。相比之下,对于 GEP 分类不充分/不满意或 GEP 类 1 肿瘤的患者,累积 5 年转移性死亡的概率为 8.0%,而对于 GEP 类 2 肿瘤的患者,这一概率为 45.0%(对数秩检验,P=0.005)。
本研究证实,FNAB 获得的后葡萄膜黑色素瘤细胞的 GEP 分类在大多数情况下是可行的,包括大多数 FNAB 抽吸物不足以进行细胞学诊断的情况。该研究还证实,GEP 分类在预测后续转移和转移性死亡方面明显优于细胞病理学分类。