Katona Terrence M, O'Malley Dennis P, Cheng Liang, Hiatt Kim M, Wang Mingsheng, Anagnostou John J, Billings Steven D, Smoller Bruce R
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Am J Surg Pathol. 2007 Oct;31(10):1552-6. doi: 10.1097/PAS.0b013e3180408d76.
Mycosis fungoides (MF) exhibits a variety of underlying molecular defects. Loss of heterozygosity (LOH) is a technique used to detect chromosomal imbalances in neoplastic disorders using archival tissue. We analyzed skin biopsies of MF in different stages for the presence of LOH at specific loci to evaluate underlying genetic aberrations involved in MF and its progression. Twenty-five skin biopsies (15 plaque stage and 10 tumor stage) from 19 patients were evaluated. LOH was examined at 1p22 (D1S2766), 9p21 [IFNA, p15 (D9S1748), p16 (D9S171)], 10q23 [PTEN (D10S185, D10S541, D10S2491)], and 17p13 [p53 (TP53)]. Abnormal lymphocytes were microdissected from formalin-fixed, paraffin-embedded tissue sections. Sixteen of the 25 (64%) specimens evaluated had at least one abnormal LOH locus and LOH was identified in 7 of 15 (47%) plaque and in 9 of 10 (90%) tumor stage lesions, respectively. All 3 patients with sequential biopsies (plaque followed by tumor lesions) had additional LOH abnormalities in tumor specimens compared with plaque stage lesions. LOH most frequently involved chromosome 10, including 7 of 10 (70%) tumor stage lesions. Loss of multiple alleles was only identified in tumor stage cases, with 3 tumors undergoing allelic losses at 3 separate loci. Our results suggest that LOH studies are a robust method for evaluating genetic abnormalities in MF. Tumor stage lesions manifest increasing allelic losses compared with plaque stage. Further, in this series, several loci associated with the tumor suppressor gene PTEN on chromosome 10 appear to be associated with progression from plaque to tumor stage.
蕈样肉芽肿（MF）存在多种潜在的分子缺陷。杂合性缺失（LOH）是一种利用存档组织检测肿瘤性疾病中染色体失衡的技术。我们分析了不同阶段MF的皮肤活检样本，检测特定基因座处的LOH，以评估参与MF及其进展的潜在基因畸变。对19例患者的25份皮肤活检样本（15份斑块期和10份肿瘤期）进行了评估。在1p22（D1S2766）、9p21 [IFNA、p15（D9S1748）、p16（D9S171）]、10q23 [PTEN（D10S185、D10S_{541}、D10S_{2491}）]和17p13 [p53（TP53）]处检测LOH。从福尔马林固定、石蜡包埋的组织切片中显微切割异常淋巴细胞。在评估的25份样本中，有16份（64%）至少有一个异常的LOH基因座，分别在15份斑块期样本中的7份（47%）和10份肿瘤期病变中的9份（90%）中检测到LOH。所有3例有连续活检样本（从斑块期到肿瘤期病变）的患者，其肿瘤样本中的LOH异常比斑块期病变更多。LOH最常累及10号染色体，在10份肿瘤期病变中有7份（70%）。多个等位基因缺失仅在肿瘤期病例中发现，有3个肿瘤在3个不同基因座发生等位基因缺失。我们的结果表明，LOH研究是评估MF基因异常的一种可靠方法。与斑块期相比，肿瘤期病变的等位基因缺失增加。此外，在本系列研究中，10号染色体上与肿瘤抑制基因PTEN相关的几个基因座似乎与从斑块期进展到肿瘤期有关。
