Phenotypic Alterations in Ductal Carcinoma In Situ-associated Myoepithelial Cells Biologic and Diagnostic Implications

Phenotypic Alterations in Ductal Carcinoma In Situ-associated Myoepithelial Cells Biologic and Diagnostic Implications
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DOI:
10.1097/pas.0b013e318180431d
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发表时间:
2009-02-01
影响因子:
5.6
通讯作者:
Collins, Laura C.
Collins, Laura C.
中科院分区:
医学1区
文献类型:
--
作者:
Hilson, Justin B.;Schnitt, Stuart J.;Collins, Laura C.

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最近的分子生物学研究表明,导管原位癌(DCIS)相关的肌上皮细胞(MEC)与正常乳腺组织中的MEC存在差异。这种改变可能会影响DCIS向浸润性癌症的进展。本研究的目的是进一步研究DCIS相关MEC的表型改变。对101例DCIS(5/6例无浸润性癌,45例伴浸润性癌)石蜡切片进行了7种MEC标志物的免疫组化染色:平滑肌肌动蛋白、平滑肌肌球蛋白重链(SMMHC)、钙调蛋白、p63、细胞角蛋白(CK)5/6、CD 10和p75。在每种情况下,将DCIS相关MEC中每种标记物的染色分布和强度与同一载玻片上正常导管小叶结构周围的MEC进行比较。与正常MEC相比,85例(84.2%)DCIS相关MEC显示一种或多种MEC标志物表达降低。显示表达降低的病例比例为76.5%,SMMHC为34.0%,CD 10为30.2%,CK 5/6为30.2%,钙调蛋白为17.4%,p63为12.6%,p75为4.2%,平滑肌肌动蛋白为1%。SMMHC的MEC表达减少在高级别DCIS中比在非高级别DCIS中更常见(84.8% vs. 61.5%的病例,P = 0.01)。我们的结论是DCIS相关的MEC显示免疫表型的差异,从周围的正常乳腺导管小叶结构的MEC。其生物学意义尚待确定。然而,这些结果表明,某些MEC市场的敏感性在DCIS相关MEC中低于正常MEC。在选择MEC标记物以帮助区分原位乳腺癌和浸润性乳腺癌时,应考虑到这一观察结果。
Recent molecular Studies have indicated that ductal carcinoma in situ (DCIS)-associated myoepithelial cells (MECs) show differences from MECs in normal breast tissue. Such alterations may influence the progression of DCIS to invasive cancer. The purpose of this study was to investigate further phenotypic alterations in DCIS-associated MECs. Paraffin sections of 101 cases of DCIS (56 without and 45 with associated invasive carcinoma) were immunostained for 7 MEC markers: smooth muscle actin, smooth muscle myosin heavy chain (SMMHC), calponin, p63, cytokeratin (CK) 5/6, CD10, and p75. In each case, the distribution and intensity of staining for each marker in DCIS-associated MECs was compared with that in MECs Surrounding normal ductal-lobular structures on the same slide. In 85 cases (84.2%), DCIS-associated MECs showed decreased expression of one or more MEC markers when compared with normal MECs. The proportion of cases that showed reduced expression was 76.5%, for SMMHC, 34.0% for CD10, 30.2% for CK5/6, 17.4% for calponin, 12.6% for p63, 4.2% for p75, and 1% for smooth muscle actin. Reduced MEC expression of SMMHC was significantly more frequent in high grade than in non-high-grade DCIS (84.8% vs. 61.5% of cases, P = 0.01). We conclude that DCIS-associated MECs show immunophenotypic differences from MECs surrounding normal mammary ductal-lobular Structures. The biologic significance of this remains to be determined. However, these results indicate that the sensitivity of some MEC markets is lower in DCIS-associated MECs than in normal MECs. This observation should be taken into consideration when selecting MEC markers to help distinguish in situ from invasive breast carcinomas.