Fujii H, Szumel R, Marsh C, Zhou W, Gabrielson E
Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland 21224, USA.
Cancer Res. 1996 Nov 15;56(22):5260-5.
To investigate the relationships of specific allelic losses to progression and histological grade of ductal carcinoma in situ (DCIS) of the breast, we studied PCR-amplified microsatellite markers on ten chromosomal arms in 41 cases of DCIS without synchronous invasive cancer. For all chromosomal arms combined, the number of allelic losses was significantly greater in lesions of intermediate or high nuclear grade (5.6 chromosomal arms/case) than in lesions of low nuclear grade (1.2 chromosomal arms/case). Allelic losses of 16q and 17p were commonly found in low nuclear grade DCIS (38 and 34%, respectively) as well as in intermediate and high nuclear grade DCIS (58 and 95%, respectively). Allelic losses of other chromosomal arms examined (1p, 1q, 6q, 9p, 11p, 11q, 13q, and 17q) were uncommonly seen in low-grade DCIS, but were seen at frequencies of greater than 40% in intermediate- and high-grade DCIS. In 10 of the cases (24%), we identified patterns of allelic loss heterogeneity suggestive of intralesional progression, findings that were possible because multiple tumor foci from each lesion were individually microdissected and studied. For these tumors with allelic loss heterogeneity, we reasoned that chromosomal losses common to all tumor foci most likely preceded the chromosomal losses observed only in tumor foci of a more advanced genetic stage. In 9 of these 10 cases, all tumor foci lost 16q, and in 8 of the 10 cases, all tumor foci lost 17p. Together, these observations indicate that chromosomal losses of 16q and 17p occur early in DCIS progression and are common even in low-grade DCIS. Tumors of intermediate and high nuclear grade usually have allelic losses of significantly more chromosomal arms, often including 1p, 1q, 6q, 9p, 11p, 11q, 13q, and 17q. Allelic loss of these chromosomal arms may occur later in DCIS progression.
为了研究特定等位基因缺失与乳腺导管原位癌（DCIS）进展及组织学分级之间的关系，我们对41例无同步浸润性癌的DCIS病例的10个染色体臂上的PCR扩增微卫星标记进行了研究。对于所有合并的染色体臂，中等或高核级病变（5.6个染色体臂/病例）的等位基因缺失数量显著多于低核级病变（1.2个染色体臂/病例）。16q和17p的等位基因缺失在低核级DCIS中常见（分别为38%和34%），在中等和高核级DCIS中也常见（分别为58%和95%）。所检测的其他染色体臂（1p、1q、6q、9p、11p、11q、13q和17q）的等位基因缺失在低级别DCIS中少见，但在中级别和高级别DCIS中的出现频率大于40%。在10例病例（24%）中，我们发现了等位基因缺失异质性模式，提示瘤内进展，之所以能发现这些结果，是因为对每个病变的多个肿瘤灶进行了单独显微切割和研究。对于这些具有等位基因缺失异质性的肿瘤，我们推断所有肿瘤灶共有的染色体缺失很可能先于仅在更晚期遗传阶段的肿瘤灶中观察到的染色体缺失。在这10例病例中的9例中，所有肿瘤灶均丢失了16q，在10例病例中的8例中，所有肿瘤灶均丢失了17p。这些观察结果共同表明，16q和17p的染色体缺失在DCIS进展早期就会出现，甚至在低级别DCIS中也很常见。中等和高核级肿瘤通常有更多染色体臂的等位基因缺失，常包括1p、1q、6q、9p、11p、11q、13q和17q。这些染色体臂的等位基因缺失可能在DCIS进展后期出现。
