Begg Colin B, Ostrovnaya Irina, Carniello Jose V Scarpa, Sakr Rita A, Giri Dilip, Towers Russell, Schizas Michail, De Brot Marina, Andrade Victor P, Mauguen Audrey, Seshan Venkatraman E, King Tari A
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
Breast Cancer Res. 2016 Jun 23;18(1):66. doi: 10.1186/s13058-016-0727-z.
Recent evidence suggests that lobular carcinoma in situ (LCIS) can be a clonal precursor of invasive breast cancers of both the ductal and lobular phenotypes. We sought to confirm these findings with an extensive study of fresh frozen breast specimens from women undergoing mastectomy.
Patients with a history of LCIS presenting for therapeutic mastectomy were identified prospectively. Frozen tissue blocks were collected, screened for lesions of interest, and subjected to microdissection and DNA extraction. Copy number profiling, whole-exome sequencing, or both were performed. Clonal relatedness was assessed using specialized statistical techniques developed for this purpose.
After exclusions for genotyping failure, a total of 84 lesions from 30 patients were evaluated successfully. Strong evidence of clonal relatedness was observed between an LCIS lesion and the invasive cancer for the preponderance of cases with lobular carcinoma. Anatomically distinct in situ lesions of both ductal and lobular histology were also shown to be frequently clonally related.
These data derived from women with LCIS with or without invasive cancer confirm that LCIS is commonly the clonal precursor of invasive lobular carcinoma and that distinct foci of LCIS frequently share a clonal origin, as do foci of LCIS and ductal carcinoma in situ.
最近的证据表明，小叶原位癌（LCIS）可能是导管和小叶两种表型浸润性乳腺癌的克隆前体。我们试图通过对接受乳房切除术的女性新鲜冷冻乳房标本进行广泛研究来证实这些发现。
前瞻性地确定有LCIS病史并接受治疗性乳房切除术的患者。收集冷冻组织块，筛选感兴趣的病变，并进行显微切割和DNA提取。进行拷贝数分析、全外显子测序或两者都进行。使用为此目的开发的专门统计技术评估克隆相关性。
在排除基因分型失败的病例后，成功评估了30例患者的84个病变。在大多数小叶癌病例中，观察到LCIS病变与浸润性癌之间存在强烈的克隆相关性证据。导管和小叶组织学上解剖学上不同的原位病变也经常显示出克隆相关性。
这些来自有或无浸润性癌的LCIS女性的数据证实，LCIS通常是浸润性小叶癌的克隆前体，并且不同的LCIS病灶经常有共同的克隆起源，LCIS病灶和导管原位癌也是如此。
