Lininger R A, Fujii H, Man Y G, Gabrielson E, Tavassoli F A
Department of Gynecologic and Breast Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA.
Mod Pathol. 1998 Dec;11(12):1151-9.
Ductal carcinoma in situ (DCIS) of the breast is often an indolent disease, although some cases are reported to recur many years after a limited surgical resection. It is not known whether these recurrences reflect a resurgence of residual disease or an independent development of a second tumor in susceptible individuals. Therefore, we conducted a longitudinal molecular study of four women with reappearance of DCIS 2 to 15 years after an initial conservative resection. Loss of heterozygosity (LOH) was characterized in both tumors in each case, using several polymerase chain reaction-amplified microsatellite markers on five chromosomal arms commonly affected in breast cancer. In three cases with ipsilateral recurrent disease, all of the allelic losses seen in the initial tumors were also seen in the recurrent lesions, suggesting a common genetic pathway for the development of both lesions and continuous proliferation of residual disease. The presence of at least one additional LOH in all of the three recurrent tumors, however, suggests that the recurrent tumors developed after genetic progression. In contrast, in one case of DCIS that was followed by the development of DCIS in the contralateral breast 7 years later (a case of bilateral DCIS), unrelated LOH patterns were present in the two lesions. These findings suggest that the reappearance of DCIS in the same breast is most commonly the result of a tumor derived from (but not identical to) the original lesion, with acquisition of additional genetic changes, even when the recurrent lesion manifested itself many years (15 years, in one case) after the initial presentation. Furthermore, genetic progression could be detected in tumors recurring in as little as 2 years after the initial resection.
乳腺导管原位癌（DCIS）通常是一种发展缓慢的疾病，不过据报道，有些病例在有限的手术切除多年后会复发。目前尚不清楚这些复发是残留疾病的复发，还是易感个体中第二种肿瘤的独立发生。因此，我们对4名女性进行了一项纵向分子研究，这些女性在初次保守切除后2至15年出现了DCIS复发。利用几种聚合酶链反应扩增的微卫星标记，对每个病例的两个肿瘤中位于乳腺癌常见受累的5个染色体臂上的杂合性缺失（LOH）进行了特征分析。在3例同侧复发病例中，初始肿瘤中出现的所有等位基因缺失在复发病变中也都可见，这表明两个病变的发生有共同的遗传途径以及残留疾病的持续增殖。然而，在所有3个复发性肿瘤中均存在至少一个额外的LOH，这表明复发性肿瘤是在基因进展后发生的。相比之下，在1例DCIS病例中，7年后对侧乳腺发生了DCIS（双侧DCIS病例），两个病变中存在不相关的LOH模式。这些发现表明，同侧DCIS的再次出现最常见的原因是源自（但不同于）原始病变的肿瘤，并伴有额外的基因变化，即使复发病变在初次出现多年（1例为15年）后才表现出来。此外，在初次切除后短短2年复发的肿瘤中就能检测到基因进展。
