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首页> 外文会议>Conference on Multiphoton Microscopy in the Biomedical Sciences >Intratumoral heterogeneity of second-harmonic generation scattering from tumor collagen and its effects on metastatic risk prediction
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Intratumoral heterogeneity of second-harmonic generation scattering from tumor collagen and its effects on metastatic risk prediction

机译：从肿瘤胶原蛋白的二次谐波产生散射的肿瘤内异质性及其对转移风险预测的影响

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摘要

Metastases are the leading cause of breast cancer-related deaths. Tumor metastasis is affected by the microenvironment, including the extracellular matrix (ECM). Fibrillar collagen in the ECM produces an intrinsic optical signal called second-harmonic generation (SHG). The ratio of forward- to backward-scattered SHG photons (F/B) is sensitive to the collagen fiber internal structure and has been shown to be an independent prognostic indicator of metastasis-free survival time. We evaluated the effects of heterogeneity in the tumor ECM on F/B's prognostic ability. Using SHG imaging we identified two distinct regions within 95 untreated primary tumor excisions: the tumor bulk and surrounding collagenous tumor-stroma interface. We found that F/B measured in the tumor-stroma interface, but not tumor bulk, is prognostic of metastasis-free survival time (MFS) using both an intensity threshold selected by a blinded observer and adaptive thresholding. We calculated a 21-gene recurrence score (surrogate OncotypeDX®, or S-ODX) for each patient and using a Random Survival Forest method we found that F/B from the tumor-stroma interface, but not tumor bulk, and S-ODX contribute to predicting MFS in this patient cohort. These results suggest that F/B from the tumor-stroma interface of primary tumor excisions may provide information independent of genomic methods to stratify patients by metastatic risk and identify need for post-operative treatment.
机译：转移是乳腺癌相关死亡的主要原因。肿瘤转移受微环境的影响，包括细胞外基质（ECM）。 ECM中的纤维状胶原蛋白产生称为二次谐波产生（SHG）的内在光信号。向后散射的SHG光子（F / B）的比率对胶原纤维内部结构敏感，并且已被证明是无异常的无转移存活时间的预后指标。我们评估了异质性在肿瘤ECM对F / B预后能力的影响。使用SHG成像我们确定了在95内未处理的原发性肿瘤发生中的两个不同区域：肿瘤散装和周围的胶原肿瘤 - 基质界面。我们发现在肿瘤 - 基质界面中测量的F / B，但不是肿瘤体积，是使用由蒙蔽观察者和自适应阈值化选择的强度阈值的无转移存活时间（MFS）的预后。我们计算每位患者的21-基因复发评分（代理oncotypedX，或S-ODX），并使用试验森林方法，我们发现来自肿瘤 - 基质界面的F / B，但不是肿瘤散装和S-ODX有助于预测该患者队列中的MFS。这些结果表明，来自原发性肿瘤发生的肿瘤 - 基质界面的F / B可以提供独立于基因组方法的信息，以通过转移风险分层患者并确定可操作性治疗的需求。

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