Department of Pathology, Ghent University and Ghent University Hospital, Ghent, Belgium.
Histopathology. 2013 Oct;63(4):520-33. doi: 10.1111/his.12188. Epub 2013 Jul 26.
The incidence of ductal carcinoma in situ (DCIS) has increased since the introduction of screening mammography. Recurrence prediction is still not accurate, and could be improved by identifying additional prognostic markers. Periductal stroma actively participates in early breast cancer progression. Therefore, the aim of this study was to explore the prognostic potential of stromal characteristics in DCIS.
Histopathological features and hormone receptor/HER2 status were analysed in a first cohort of 65 cases of DCIS with a median follow-up of 112 months. Cox regression analysis revealed that myxoid stromal architecture was significantly associated with increased ipsilateral locoregional recurrence (P = 0.015). Next, we performed immunohistochemical screening of nine stromal proteins in a second cohort of 82 DCIS cases, and correlated their expression with stromal architecture. Because reduced stromal decorin expression correlated most strongly with myxoid stroma (P < 0.001), it was selected for further analysis in the first cohort. Patients with reduced periductal decorin expression had a higher risk of recurrence (P = 0.008). Furthermore, HER2 overexpression was significantly associated with invasive but not with in situ recurrence (P = 0.007).
Periductal myxoid stroma and reduced periductal decorin expression seem to be prognostic for overall ipsilateral locoregional recurrence in DCIS, whereas HER2 expression might be a more specific biomarker for invasive recurrence.
自乳腺筛查钼靶摄影问世以来,导管原位癌(DCIS)的发病率有所增加。目前对其复发的预测仍不够准确,可能需要通过识别其他预后标志物来加以改善。周围间质积极参与早期乳腺癌的进展。因此,本研究旨在探讨 DCIS 中间质特征的预后潜力。
对 65 例 DCIS 患者的组织病理学特征和激素受体/HER2 状态进行了分析,其中位随访时间为 112 个月。Cox 回归分析显示,黏液样间质结构与同侧局部复发风险增加显著相关(P=0.015)。随后,我们在 82 例 DCIS 患者的第二个队列中进行了 9 种间质蛋白的免疫组织化学筛选,并将其表达与间质结构相关联。由于基质中核心蛋白聚糖表达减少与黏液样间质相关性最强(P<0.001),因此选择其在第一个队列中进一步分析。核心蛋白聚糖表达减少的患者复发风险更高(P=0.008)。此外,HER2 过表达与浸润性而非原位复发显著相关(P=0.007)。
周围管周黏液样间质和核心蛋白聚糖表达减少似乎是 DCIS 总体同侧局部复发的预后指标,而 HER2 表达可能是浸润性复发的更特异的生物标志物。