Collagen Alignment as a Predictor of Recurrence after Ductal Carcinoma In Situ.
Collagen Alignment as a Predictor of Recurrence after Ductal Carcinoma In Situ.
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DOI：
10.1158/1055-9965.epi-17-0720
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发表时间：
2018-03
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影响因子：
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通讯作者：
Trentham-Dietz A
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作者：
Conklin MW;Gangnon RE;Sprague BL;Van Gemert L;Hampton JM;Eliceiri KW;Bredfeldt JS;Liu Y;Surachaicharn N;Newcomb PA;Friedl A;Keely PJ;Trentham-Dietz A
乳腺导管周围的胶原纤维可能会影响乳腺癌的进展。Syndecan-1与细胞外基质中的成分（包括胶原纤维）相互作用，并可能有助于癌细胞迁移。因此，导管原位癌（DCIS）病变周围胶原纤维的取向和间质syndecan-1表达可能预测复发。我们评估了1995-2006年至2014年诊断为DCIS的227名女性的胶原纤维排列和syndecan-1表达（中位数14.5年，范围0.7-17.6）。使用二次谐波发生显微镜和纤维分析软件从诊断组织载玻片评价基质胶原对齐。采用卡方检验和方差分析进行单变量分析。使用风险比（HR）和95%置信区间（CI）评估胶原对齐Z评分、syndecan-1染色强度和复发时间之间的相关性。DCIS病变周围较大的纤维角度，而不是syndecan-1染色强度，与阳性HER 2（p=0.002）状态、粉刺坏死（p=0.03）和阴性雌激素受体（p=0.002）和孕激素受体（p=0.02）状态相关。病变周围的纤维角度分布包括比正常导管更接近90度的角度（p=0.06）。DCIS病变的胶原排列Z评分与复发呈正相关（HR 1.25，平均纤维角四分位数间距增加的95% CI 0.84-1.87）。虽然胶原排列和间质syndecan-1表达不能预测复发，但在具有典型预后不良特征的DCIS病变中，垂直于导管周边的胶原纤维更常见。后续研究是必要的，以检查是否胶原蛋白基质的其他功能可能更强有力地预测患者的结果。
Collagen fibers surrounding breast ducts may influence breast cancer progression. Syndecan-1 interacts with constituents in the extracellular matrix, including collagen fibers, and may contribute to cancer cell migration. Thus, the orientation of collagen fibers surrounding ductal carcinoma in situ (DCIS) lesions and stromal syndecan-1 expression may predict recurrence. We evaluated collagen fiber alignment and syndecan-1 expression in 227 women diagnosed with DCIS in 1995–2006 followed through 2014 (median 14.5 years, range 0.7–17.6). Stromal collagen alignment was evaluated from diagnostic tissue slides using second harmonic generation microscopy and fiber analysis software. Univariate analysis was conducted using chi-square tests and analysis of variance. The association between collagen alignment Z-scores, syndecan-1 staining intensity, and time to recurrence was evaluated using hazard ratios (HR) and 95% confidence intervals (CI). Greater fiber angles surrounding DCIS lesions, but not syndecan-1 staining intensity, were related to positive HER2 (p=0.002) status, comedo necrosis (p=0.03), and negative estrogen receptor (p=0.002) and progesterone receptor (p=0.02) status. Fiber angle distributions surrounding lesions included more angles closer to 90-degrees than normal ducts (p=0.06). Collagen alignment Z-scores for DCIS lesions were positively related to recurrence (HR 1.25, 95% CI 0.84–1.87 for an interquartile range increase in average fiber angles). Although collagen alignment and stromal syndecan-1 expression did not predict recurrence, collagen fibers perpendicular to the duct perimeter were more frequent in DCIS lesions with features typical of poor prognosis. Follow-up studies are warranted to examine whether additional features of the collagen matrix may more strongly predict patient outcomes.