Abstract
Hyaluronan (HA) is an extracellular matrix component that plays an important role in a diverse range of cellular processes including proliferation, tissue hydration, cell motility, inflammation, angiogenesis, and malignancy. Increased HA deposition is a characteristic of many desmoplastic tumors. High HA levels have been correlated with poor prognosis in some cancer types, including gastric, colorectal, breast, ovarian, and bladder cancers. Considering the high desmoplastic stromal content of pancreatic tumors, we hypothesized that high HA levels may contribute to poor prognosis or survival in pancreatic cancer. Utilizing a biotinylated HA binding protein-based staining method in a tissue microarray constructed from resected pancreatic tumor tissues, we assessed HA-specific staining in 43 pancreatic ductal adenocarcinoma samples for which patient survival had been followed for more than eight years. We observed HA staining primarily in the peritumoral, or stromal, compartment of the tumor tissue samples. 100% of the patient tumors stained positive in at least some fraction of the tissue area (stroma) for HA. The staining was scored according to the percentage area of HA-positivity, relative to total tissue area. We observed low (<40%) and high (≥40%) levels of stromal HA in 11 and 32 patient samples, respectively. We tested our hypothesis with the log-rank test and found that the survival rate was significantly lower among patients with high HA (P<0.05). The median survival among those patients with high HA was 299 days, and 738 days for those with low HA (the difference in median survival between the two patient groups is 439 days). These results suggest that HA levels in pancreatic adenocarcinoma patients may be predictive of survival. Because HA functions in maintaining high tumoral interstitial fluid pressure, resulting in vascular compression and limited tumor-drug access, our results also suggest that HA may serve as a potential therapeutic target in pancreatic cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-307. doi:10.1158/1538-7445.AM2011-LB-307
- ©2011 American Association for Cancer Research
Volume 71, Issue 8 Supplement
