TY - JOUR
T1 - Desmoplasia in primary tumors and metastatic lesions of pancreatic cancer
AU - Whatcott, Clifford J.
AU - Diep, Caroline H.
AU - Jiang, Ping
AU - Watanabe, Aprill
AU - Lobello, Janine
AU - Sima, Chao
AU - Hostetter, Galen
AU - Shepard, H. Michael
AU - Von Hoff, Daniel D.
AU - Han, Haiyong
N1 - Publisher Copyright:
© 2015 American Association for Cancer Research.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - 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 latestage, metastatic disease. Experimental Design: We sought to assess desmoplasia in metastatic lesions of PDAC and compare it with that of primary tumors. Fifty-three patients' primaries and 57 patients' metastases were stained using IHC 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 with 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. Conclusions: Our results suggest that both primary tumors and metastases of PDAC have highly fibrotic stroma. Thus, stromal targeting agents have the potential to benefit PDACpatients, even those with metastatic disease.
AB - 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 latestage, metastatic disease. Experimental Design: We sought to assess desmoplasia in metastatic lesions of PDAC and compare it with that of primary tumors. Fifty-three patients' primaries and 57 patients' metastases were stained using IHC 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 with 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. Conclusions: Our results suggest that both primary tumors and metastases of PDAC have highly fibrotic stroma. Thus, stromal targeting agents have the potential to benefit PDACpatients, even those with metastatic disease.
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U2 - 10.1158/1078-0432.CCR-14-1051
DO - 10.1158/1078-0432.CCR-14-1051
M3 - Article
C2 - 25695692
AN - SCOPUS:84938648673
SN - 1078-0432
VL - 21
SP - 3561
EP - 3568
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 15
ER -