Lichy J H, Zavar M, Tsai M M, O'Leary T J, Taubenberger J K
Molecular Pathology Division, Department of Cellular Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA.
Am J Pathol. 1998 Jul;153(1):271-8. doi: 10.1016/S0002-9440(10)65568-X.
Microdissection of histologically identifiable components from formalin-fixed, paraffin-embedded tissue sections allows molecular genetic analyses to be correlated directly with pathological findings. In this study, we have characterized loss of heterozygosity (LOH) at chromosome 11p15 at different stages of progression in microdissected tumor components from 115 ductal carcinomas of the breast. Microdissected foci of intraductal, infiltrating, and metastatic tumors were analyzed to determine the stage of progression at which LOH at 11p15 occurs. LOH was detected in 43 (37%) of 115 cases. Foci of intraductal carcinoma could be microdissected from 85 cases, of which 30 (35%) showed LOH at some stage of progression. LOH was detected in the intraductal component in 26 of these 30 cases. Interstitial deletions were characterized by using a panel of 10 highly polymorphic markers. The smallest region of overlap (SRO) for LOH at 11p15 was bounded by the markers D11S4046 and D11S1758. LOH at 11p15.5 showed no correlation with estrogen receptor status, the presence of positive lymph nodes, tumor size, histological grade, or long-term survival. We conclude that 11p15 LOH usually occurs early in breast cancer development but less frequently does not develop until the infiltrating or metastatic stages of tumor progression.
从福尔马林固定、石蜡包埋的组织切片中显微切割出组织学上可识别的成分，能使分子遗传学分析直接与病理结果相关联。在本研究中，我们对115例乳腺导管癌显微切割的肿瘤成分在不同进展阶段11号染色体p15区域的杂合性缺失（LOH）进行了特征分析。对显微切割的导管内、浸润性和转移性肿瘤灶进行分析，以确定11p15区域发生LOH的进展阶段。115例病例中有43例（37%）检测到LOH。85例病例可显微切割出导管内癌灶，其中30例（35%）在进展的某个阶段显示出LOH。这30例中的26例在导管内成分中检测到LOH。通过使用一组10个高度多态性标记对间质缺失进行了特征分析。11p15区域LOH的最小重叠区域（SRO）由标记D11S4046和D11S1758界定。11p15.5区域的LOH与雌激素受体状态、阳性淋巴结的存在、肿瘤大小、组织学分级或长期生存均无相关性。我们得出结论，11p15区域的LOH通常在乳腺癌发展的早期发生，但在肿瘤进展到浸润或转移阶段才发生的情况较少见。
