Desmoplasia in Primary Tumors and Metastatic Lesions of Pancreatic Cancer.
Desmoplasia in Primary Tumors and Metastatic Lesions of Pancreatic Cancer.
复制标题
DOI：
10.1158/1078-0432.ccr-14-1051
复制
发表时间：
2015-08-01
期刊：
影响因子：
--
通讯作者：
Han H
中科院分区：
文献类型：
--
作者：
Whatcott CJ;Diep CH;Jiang P;Watanabe A;LoBello J;Sima C;Hostetter G;Shepard HM;Von Hoff DD;Han H
胰腺导管腺癌 (PDAC) 的特点是高水平纤维化，称为结缔组织增生，这被认为会阻碍 PDAC 治疗的疗效。我们的主要重点是评估原发性肿瘤和转移性病变中结缔组织增生程度的差异。由于转移负担是 PDAC 死亡的主要原因，因此转移灶中结缔组织增生的程度可能有助于确定结缔组织增生靶向治疗是否有益于晚期转移性疾病患者。我们试图评估 PDAC 转移性病变中的结缔组织形成，并将其与原发性肿瘤进行比较。使用免疫组织化学染色技术对 53 名患者的原发灶和 57 名患者的转移灶进行了染色。我们观察到患者生存率与原发性肿瘤细胞外基质沉积之间存在显着负相关。胶原蛋白 I 的 Kaplan-meier 曲线显示，低胶原蛋白患者的中位生存期为 14.6 个月，高胶原蛋白水平患者的中位生存期为 6.4 个月（对数等级，P<0.05）。低水平透明质酸患者的中位生存时间为 24.3 个月，而高水平患者的中位生存时间为 9.3 个月（对数等级，P<0.05）。我们的分析还表明，细胞外基质成分，如胶原蛋白和透明质酸，在原发性肿瘤和转移性病灶中含量很高。原发肿瘤和转移病灶之间的结缔组织增生水平差异无统计学意义。我们的结果表明，PDAC 的原发肿瘤和转移瘤均具有高度纤维化的基质。因此，基质靶向剂有可能使 PDAC 患者受益，甚至是那些患有转移性疾病的患者。
Pancreatic ductal adenocarcinoma (PDAC) is characterized by high levels of fibrosis, termed desmoplasia, which is thought to hamper the efficacy of therapeutics treating PDAC. Our primary focus was to evaluate differences in the extent of desmoplasia in primary tumors and metastatic lesions. As metastatic burden is a primary cause for mortality in PDAC, the extent of desmoplasia in metastases may help to determine whether desmoplasia targeting therapeutics will benefit patients with late stage, metastatic disease. We sought to assess desmoplasia in metastatic lesions of PDAC and compare it to that of primary tumors. Fifty three patients’ primaries and fifty seven patients’ metastases were stained using immunohistochemical staining techniques. We observed a significant negative correlation between patient survival and extracellular matrix deposition in primary tumors. Kaplan-meier curves for Collagen I showed median survival of 14.6 months in low collagen patients, and 6.4 months in high level patients (log rank, P<0.05). Low level hyaluronan patients displayed median survival times of 24.3 months as compared to 9.3 months in high level patients (log rank, P<0.05). Our analysis also indicated that extracellular matrix components, such as collagen and hyaluronan, are found in high levels in both primary tumors and metastatic lesions. The difference in the level of desmoplasia between primary tumors and metastatic lesions was not statistically significant. Our results suggest that both primary tumors and metastases of PDAC have highly fibrotic stroma. Thus, stromal targeting agents have the potential to benefit PDAC patients, even those with metastatic disease.