Man Yan-gao, Tai Lisa, Barner Ross, Vang Russell, Saenger Jeffrey S, Shekitka Kris M, Bratthauer Gary L, Wheeler Darren T, Liang Chang Y, Vinh Tuyethoa N, Strauss Brian L
Department of Gynecologic and Breast Pathology, Armed Forces Institute of Pathology and American Registry of Pathology, Washington, DC, USA.
Breast Cancer Res. 2003;5(6):R231-41. doi: 10.1186/bcr653. Epub 2003 Oct 3.
Our previous studies detected focal disruptions in myoepithelial cell layers of several ducts with carcinoma in situ. The cell cluster overlying each of the myoepithelial disruptions showed a marked reduction in or a total loss of immunoreactivity for the estrogen receptor (ER). This is in contrast to the adjacent cells within the same duct, which were strongly immunoreactive for the ER. The current study attempts to confirm and expand previous observations on a larger scale.
Paraffin sections from 220 patients with ER-positive intraductal breast tumors were double immunostained with the same protocol previously used. Cross-sections of ducts lined by > or = 40 epithelial cells were examined for myoepithelial cell layer disruptions and for ER expression. In five selected cases, ER-negative cells overlying the disrupted myoepithelial cell layer and adjacent ER-positive cells within the same duct were separately microdissected and assessed for loss of heterozygosity and microsatellite instability.
Of the 220 cases with 5698 duct cross-sections examined, 94 showed disrupted myoepithelial cell layers with 405 focal disruptions. Of the 94 cases, 79 (84%) contained only ER-negative cell clusters, nine (9.6%) contained both ER-negative and ER-positive cell clusters, and six (6.4%) contained only ER-positive cell clusters overlying disrupted myoepithelial cell layers. Of the 405 disruptions, 350 (86.4%) were overlain by ER-negative cell clusters and 55 (13.6%) were overlain by ER-positive cell clusters (P < 0.01). Microdissected ER-negative and ER-positive cells within the same duct from all five selected cases displayed a different frequency or pattern of loss of heterozygosity and/or microsatellite instability at 10 of the 15 DNA markers.
Cells overlying focally disrupted myoepithelial layers and their adjacent counterparts within the same duct displayed different immunohistochemical and molecular features. These features potentially represent an early sign of the formation of a biologically more aggressive cell clone and the myoepithelial cell layer breakdown possibly associated with tumor progression or invasion.
我们之前的研究在几例原位癌的导管肌上皮细胞层中检测到局灶性破坏。覆盖在每个肌上皮破坏部位上方的细胞簇显示雌激素受体（ER）免疫反应性显著降低或完全丧失。这与同一导管内相邻细胞形成对比，相邻细胞对ER呈强免疫反应性。本研究试图在更大规模上证实并扩展先前的观察结果。
对220例ER阳性乳腺导管内肿瘤患者的石蜡切片采用先前使用的相同方案进行双重免疫染色。检查由≥40个上皮细胞构成的导管横切面，以观察肌上皮细胞层破坏情况及ER表达。在5例选定病例中，分别对覆盖在破坏的肌上皮细胞层上方的ER阴性细胞和同一导管内相邻的ER阳性细胞进行显微切割，并评估杂合性缺失和微卫星不稳定性。
在检查的220例病例共5698个导管横切面中，94个显示肌上皮细胞层破坏，有405个局灶性破坏部位。在这94例中，79例（84%）仅含有ER阴性细胞簇，9例（9.6%）同时含有ER阴性和ER阳性细胞簇，6例（6.4%）在破坏肌上皮细胞层上方仅含有ER阳性细胞簇。在405个破坏部位中，350个（86.4%）被ER阴性细胞簇覆盖且55个（13.6%）被ER阳性细胞簇覆盖（P<0.01）。从所有5例选定病例的同一导管内显微切割得到的ER阴性和ER阳性细胞在15个DNA标记中的10个显示出不同频率或模式的杂合性缺失和/或微卫星不稳定性。
覆盖在局灶性破坏肌上皮层上方的细胞及其在同一导管内的相邻细胞表现出不同的免疫组化和分子特征。这些特征可能代表生物学上更具侵袭性的细胞克隆形成的早期迹象，且肌上皮细胞层的破坏可能与肿瘤进展或侵袭相关。
