Using second harmonic generation to predict patient outcome in solid tumors.
Using second harmonic generation to predict patient outcome in solid tumors.
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DOI：
10.1186/s12885-015-1911-8
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发表时间：
2015-11-24
期刊：
影响因子：
3.8
通讯作者：
Brown E
中科院分区：
文献类型：
--
作者：
Burke K;Smid M;Dawes RP;Timmermans MA;Salzman P;van Deurzen CH;Beer DG;Foekens JA;Brown E
雌激素受体阳性(ER+)、淋巴结阴性(LNN)乳腺癌患者的化疗过度治疗是一个紧迫的临床问题，可以通过改进预测肿瘤转移潜力的技术来解决。在这里，我们证明，分析原发肿瘤活检组织中的二次谐波产生(SHG)发射方向可以为ER+、LNN乳腺癌以及1期结直肠癌的转移结果提供预后信息。倍频是一种由胶原纤维产生的光信号。前向与后向倍频信号的比值(F/B)对单个胶原纤维结构的变化很敏感。对未接受系统辅助治疗的LNN乳腺癌患者进行了原发肿瘤切除组织的F/B测定，并与无转移生存率(MFS)和总生存率(OS)进行了相关分析。此外，在接受他莫昔芬作为一线治疗复发疾病的ER+患者亚组中，研究了F/B与无进展生存期(PFS)的关系，以及在I期结直肠癌和1期肺腺癌患者中F/B与OS的关系。在12 5例ER+，而96例ER阴性(ER-)的乳腺癌患者中，F/B升高与MFS和OS显著相关(MFS的对数趋势：P = 0.004，OS的对数趋势：P = 0.0 3)。另一方面，在接受三苯氧胺治疗的60例ER+复发乳腺癌患者中，F/B比值的增加与较短的PFS相关(对数趋势p = 0.02)。在I期结直肠癌中，F/B升高与OS差显著相关(对数等级趋势p = 0.0 3)，而在I期肺腺癌中这种关系无统计学意义。在ER+，LNN乳腺癌样本中，F/B可以根据患者的肿瘤侵袭性潜力对患者进行分层。这提供了一种“以基质为中心”的方法来预测转移结果，这是对基因组“以细胞为中心”方法的补充。这种方法和其他方法结合起来，可能有助于改善转移预测，因此可能有助于减少患者过度治疗。
Over-treatment of estrogen receptor positive (ER+), lymph node-negative (LNN) breast cancer patients with chemotherapy is a pressing clinical problem that can be addressed by improving techniques to predict tumor metastatic potential. Here we demonstrate that analysis of second harmonic generation (SHG) emission direction in primary tumor biopsies can provide prognostic information about the metastatic outcome of ER+, LNN breast cancer, as well as stage 1 colorectal adenocarcinoma. SHG is an optical signal produced by fibrillar collagen. The ratio of the forward-to-backward emitted SHG signals (F/B) is sensitive to changes in structure of individual collagen fibers. F/B from excised primary tumor tissue was measured in a retrospective study of LNN breast cancer patients who had received no adjuvant systemic therapy and related to metastasis-free survival (MFS) and overall survival (OS) rates. In addition, F/B was studied for its association with the length of progression-free survival (PFS) in a subgroup of ER+ patients who received tamoxifen as first-line treatment for recurrent disease, and for its relation with OS in stage I colorectal and stage 1 lung adenocarcinoma patients. In 125 ER+, but not in 96 ER-negative (ER-), LNN breast cancer patients an increased F/B was significantly associated with a favorable MFS and OS (log rank trend for MFS: p = 0.004 and for OS: p = 0.03). On the other hand, an increased F/B was associated with shorter PFS in 60 ER+ recurrent breast cancer patients treated with tamoxifen (log rank trend p = 0.02). In stage I colorectal adenocarcinoma, an increased F/B was significantly related to poor OS (log rank trend p = 0.03), however this relationship was not statistically significant in stage I lung adenocarcinoma. Within ER+, LNN breast cancer specimens the F/B can stratify patients based upon their potential for tumor aggressiveness. This offers a “matrix-focused” method to predict metastatic outcome that is complementary to genomic “cell-focused” methods. In combination, this and other methods may contribute to improved metastatic prediction, and hence may help to reduce patient over-treatment.