Li H, Chen Q, Zhu R, Gu D H, Zhu H G
Department of Pathology, Shanghai Medical Colege of Fudan University, Shanghai, 200032, China.
Neoplasma. 2007;54(6):490-4.
Recently, it is accepted that invasive breast carcinoma is of monoclonal origin. Ductal intraepithelial neoplasia (DIN) may progress toward invasive carcinoma with an increased risk. However, it is not fully understood whether DIN is polyclonal or monoclonal. In this current study, we detected clonal origin of DIN using x-inactivation at the human androgen receptor (HUMARA) locus. Lesional and normal breast gland cells were microdissected from paraffin-embedded tissues using a laser capture microdissection system. Genomic DNA was extracted. After digestion by restriction enzyme Hpa II, the HUMARA exon1 was amplified by a fluorescent nested-PCR procedure and the PCR products were separated on DNA sequencer and analyzed the fluorescent intensity of the two HUMARA alleles. DNA from 88 of 101(87%) patients was able to be amplified at the HUMARA locus and 68 of them (77.3%) were heterozygous and informative. 9/12 usual ductal hyperplasia (UDH) and 5/18 DIN 1A showed a polyclonal inactivation. 3/12 UDH, 13/18 DIN 1A, 28/28 DIN 1B, 10/10 carcinoma in situ are of monoclonal origin. Taken together, DIN 1A, 1B and carcinoma in situ, are monoclonal and DIN 1, but not UDH, represents the obligate and direct precursor of DCIS.
最近，人们普遍认为浸润性乳腺癌起源于单克隆。导管原位上皮内瘤变（DIN）可能会进展为浸润性癌，风险增加。然而，DIN是多克隆还是单克隆尚未完全明确。在本研究中，我们利用人类雄激素受体（HUMARA）位点的X染色体失活检测DIN的克隆起源。使用激光捕获显微切割系统从石蜡包埋组织中显微切割病变和正常乳腺细胞。提取基因组DNA。用限制性内切酶Hpa II消化后，通过荧光巢式PCR扩增HUMARA外显子1，PCR产物在DNA测序仪上分离，并分析两个HUMARA等位基因的荧光强度。101例患者中有88例（87%）的DNA能够在HUMARA位点扩增，其中68例（77.3%）为杂合且信息丰富。12例普通导管增生（UDH）中有9例和18例DIN 1A中有5例表现为多克隆失活。12例UDH中有3例、18例DIN 1A中有13例、28例DIN 1B中有28例、10例原位癌起源于单克隆。综上所述，DIN 1A、1B和原位癌是单克隆的，而DIN 1（而非UDH）是导管原位癌（DCIS）的直接前体。
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