Correlation between immunohistochemical Expressions of Somatostatin Receptor (SSTR)2a & mTOR and Clinical Response by Octreotide & Everolimus in Metastatic Pancreatic Neuroendocrine Tumors (PNET) in the Liver: A First Report on the Predictive Role of SSTR and mTOR in the Large Series of Referred Cases
Robert Y Osamura, Midori Matsuda, Chie Inomoto, Hiroshi Kajiwara. International University of Health and Welfare Mita Hospital, Mita, Tokyo, Japan; Tokai University School of Medicine, Isehara, Kanagawa, Japan
Background: Currently, for PNETs, targeted therapeutic approaches include somatostatin analogue(octreotide) and mTOR inhibitor(everolimus). This study is aimed at to elucidate the expression rate of SSTR2a,a target for octreotide in a large series of neuroendocrine tumors(NET) and to further elucidate the relationship between immunohistochemistry of SSTR2a & mTOR and clinical responses to octreotide & everolimus in the selected cases of metastatic PNETs in the liver. This is the first study on the predictive role of SSTR and mTOR.
Design: Total 269 referred cases of NET were immunohistochemically stained for SSTR2a(antibody supplied by EPITOMICS®). Among these, total 17 cases with metastatic PNETs in the liver were further subjected to immunohistochemical staining for phosphorylated(p)-mTOR(antibody supplied by Cell Signaling®), For SSTR2a, the interpretation was done according to Volante et al.(2007). The cytoplasmic p-mTOR was interpreted positive according to both positive areas(>1%) and intensity(1+,2+,3+). Clinical condition after the therapy was either (1)tumor shrunken,(2)stable disease(SD) or (3)tumor recurred or enlarged.
Results: Among 269 cases, SSTR2a was positive(score 2 and 3) in 61% of cases. The selected 17 PNET cases with metastases were treated with octreotide and/or everolimus according to the immunohistochemical expression of SSTR2a and p–mTOR. Among 7 cases with the tumors which were positive only for SSTR2a, clinical response was SD in 5 cases(71%). Two tumors were enlarged after the therapy. The other four cases were both positive for SSTR2a & p-mTOR, three of them were treated with both octreotide & everolimus. Two case showed SD(67%) and one recurred. Another case was treated with only everolimus and the response was SD. One case of PNET in VHL family with negative p-mTOR did not respond to everolimus.
Conclusions: Overall positive rate for SSTR2a was 61%. For the metastatic cases with positive for SSTR2a or positive for both SSTR2a & p-mTOR, clinical response with octreotide or octreotide & everolimus was 71% and 67% respectively. The p-mTOR negative VHL-related PNET was unresponsive to everolimus treatment. This is the first report which suggests the predictive role of SSTR2a and p-mTOR detection in the targeted therapy for the metastatic PNET.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 64, Wednesday Afternoon