An Analysis of Protein Expressions of Pancreatic Neuroendocrine Tumors of Japanease Patients According to 2010 WHO Classification
Atsuko Kasajima, Kazuyuki Ishida, Fumiyoshi Fujishima, Fuyuhiko Motoi, Hideo Ootsuka, Yasuhiro Nakamura, Mika Watanabe, Michiaki Unno, Hironobu Sasano. Tohoku University Hospital, Sendai, Japan
Background: Results of recent epidermiological studies of neuroendocrine tumor (NET) in Japan demonstrated marked differences in the incidence and locations of the patients between Japan and Western countries. Previous studies have demonstrated the biological interactions among mammalian target of rapamycin (mTOR) signaling pathways, growth factor receptors, such as epidermal growth factor receptor (EGFR), angiogenesis, and anti-angiogenetic actions mediated by somatostatin receptors (SSTRs) in NET. However the status of these factors in Japanese PNET patients has not been studied in details. We therefore evaluated the status of tumor growth regulators, such as mTOR or EGFR, and anti-proliferative regulators, such as SSTRs in order to understand their clinical and/or biological significance in Japanese PNET patients.
Design: Immunoreactivity of hypoxia induced factor 1a (HIF1a), vascular endothelial growth factor (VEGF), mTOR and EGFR were semiquantitatively assessed in 62 cases of surgically resected Japanese PNET cases. Membranous immunoreactivity of five subtypes of SSTRs (1, 2a, 2b, 3, 5) was regarded as positive. The immunoreactivity was compared to clinicopathological findings as well as the new grading system according to WHO classification, tumor size and metastatic status.
Results: Tumor grading of the cases according to WHO2010 was G1: 46.8%, G2: 48.4% and G3: 4.8%. HIF1a, VEGF, mTOR and EGFR were detected in 50 (70.4%), 53 (74.6%), 48 (67.6%) and 29cases(40.8%), respectively. The status of HIF1a and EGFR in G3 NET was significantly higher than in G1/2 NET patients (p=0.026, p=0.014, respectively). No significant association was detected between WHO2010 Grade and VEGF and mTOR status of the tumor.
Conclusions: A significant positive correlation was detected between tumor grading according to WHO 2010 and the status of HIF1a and EGFR in tumor cells. However, VEGF and mTOR status was not significantly associated with with tumor grading. In addition, the status of SSTRs, which have been demonstrated to play pivotal roles in anti-proliferative activities of tumor cells, was not significantly correlated with tumor grading of the Japanese NET patients in our present study, possibly due to relatively low proliferative status of the cases examined. Results of our present study also suggest that both HIF1a and EGFR play important roles in tumor proliferation in Japanese PNET patients.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 43, Tuesday Afternoon