Maat Willem, Jordanova Ekaterina S, van Zelderen-Bhola Shama L, Barthen Ed R, Wessels Hans W, Schalij-Delfos Nicoline E, Jager Martine J
Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands.
Arch Pathol Lab Med. 2007 Jan;131(1):91-6. doi: 10.5858/2007-131-91-THDOMI.
The detection of monosomy 3 in uveal melanomas has repeatedly been associated with adverse outcome. Fine-needle aspiration biopsy is being used to detect monosomy 3 in these tumors, based on the assumption that this chromosomal abnormality is distributed homogeneously throughout the tumor.
To study the distribution of monosomy 3 in primary uveal melanoma by fluorescence in situ hybridization (FISH).
We studied 50 enucleated eyes with uveal melanoma. In all 50 tumors we performed cytogenetic analysis and FISH using a DNA-specific probe for the centromere region of chromosome 3 on cultured tumor cells. In addition, the percentage of tumor cells with monosomy 3 was assessed by FISH on nuclei, isolated from paraffin-embedded tissue and compared to results of FISH on regular histology sections of the paraffin-embedded tissue.
Combining karyotyping and FISH on cultured cells identified monosomy 3 in 19 (38%) of 50 tumors, whereas FISH on nuclei isolated from paraffin-embedded tissue showed 31 (62%) of 50 as having monosomy for chromosome 3. FISH analysis on paraffin sections showed tumor heterogeneity for copy number of chromosome 3 in at least 7 cases.
FISH analysis on paraffin sections shows that heterogeneity of monosomy of chromosome 3 is a frequent phenomenon in uveal melanoma. FISH on nuclei isolated from paraffin-embedded tissue identifies a higher frequency of monosomy 3 than the traditional combination of karyotyping and FISH on cultured uveal melanoma cells. The practice of assigning patients to risk categories based on fine-needle aspiration biopsy samples from primary uveal melanoma may be subject to error based on the heterogeneous distribution of monosomy 3 in these tumors.
葡萄膜黑色素瘤中3号染色体单体的检测多次与不良预后相关。细针穿刺活检被用于检测这些肿瘤中的3号染色体单体，基于这样的假设，即这种染色体异常在整个肿瘤中均匀分布。
通过荧光原位杂交（FISH）研究原发性葡萄膜黑色素瘤中3号染色体单体的分布。
我们研究了50只摘除眼球的葡萄膜黑色素瘤。在所有50个肿瘤中，我们对培养的肿瘤细胞进行了细胞遗传学分析和使用针对3号染色体着丝粒区域的DNA特异性探针的FISH。此外，通过对从石蜡包埋组织中分离的细胞核进行FISH评估具有3号染色体单体的肿瘤细胞百分比，并与石蜡包埋组织常规组织学切片上的FISH结果进行比较。
对培养细胞进行核型分析和FISH相结合，在50个肿瘤中的19个（38%）中鉴定出3号染色体单体，而对从石蜡包埋组织中分离的细胞核进行FISH显示，50个中有31个（62%）具有3号染色体单体。对石蜡切片的FISH分析显示，至少7例中3号染色体拷贝数存在肿瘤异质性。
对石蜡切片的FISH分析表明，3号染色体单体的异质性在葡萄膜黑色素瘤中是一种常见现象。对从石蜡包埋组织中分离的细胞核进行FISH比传统的对培养的葡萄膜黑色素瘤细胞进行核型分析和FISH相结合能鉴定出更高频率的3号染色体单体。基于原发性葡萄膜黑色素瘤细针穿刺活检样本将患者分配到风险类别中的做法可能会因这些肿瘤中3号染色体单体的异质性分布而出现误差。
