Desmoplasia in primary tumors and metastatic lesions of pancreatic cancer
A partir d'échantillons de tumeurs primitives et de métastases prélevés sur 53 patients atteints d'un adénocarcinome canalaire du pancréas, cette étude suggère que les tumeurs primitives et les métastases sont dotées d'un stroma fibreux similaire
Purpose : 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. Experimental Design : 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. Results : 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. Conclusion : 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.