Immunohistochemical Detection of Somatostatin Receptor 2a (SSTR2a) and mTOR in the Cases of Neuroendocrine Tumors (NETs) for Appropriate Biotherapy; Experience of a Large Series of Referred Cases
Robert Y Osamura, Midori Matsuda, Taro Itoh, Cie Inomoto, Hiroshi Kajiwara. Center for Diagnostic Pathology International University of Health and Welfare(IUHW), IUHW Mita Hospital, Minato-ku, Tokyo, Japan; Tokai University School of Medicine, Isehara, Japan
Background: Somatostatin analoq(SA) is effective in 70% of cases of NET when the tumor cells are immunohistochemically positive for SSTR2a(USCAP 2011). Everolimus inhibits mammalian target of rapamycin(mTOR) and is used for cancer therapy. This study is aimed at to elucidate the overall immunohistochemical positive rate for SSTR2a in a large series of annually increasing 202 referred cases of NETs and, in the selected cases of metastatic pancreatic neuroendocrine carcinoma(NEC) in the liver, to further elucidate both SSTR2a and mTOR in order to suggest the feasibility of mono- or combined biotherapy in this difficult clinical condition.
Design: Formaling-fixed paraffin sections of total 202 cases(since 2006) of NETs(38%pancreas, 8%duodenum, 6%stomach,7%rectum, 23% liver metastases, 16% others) were subjected to the immunohistochemical staining for SSTR2a with specific antibody(Gramsch Laboratories,Gemany). In selected 28 cases of metastatic pancreatic NEC in the lver, immunohistochemical detection of mTOR was also performed using antibody against bioactive phosphorylated mTOR(Cell Signaling Technology,USA).
Results: 59% of all cases were positive for SSTR2a(Volante score 2 and 3)(Fig). In selected 28 cases of liver metastases of pancreatic NEC, 19 cases(69%) were positive for SSTR2a. mTOR was positive in the cytoplasm in total nine cases(32%). Three cases showed the positive staining in more than 20% of the tumor cells with moderate to intense cytoplasmic staining. One case with strong mTOR staining was negative for SSTR2a.
Conclusions: Increase in cases for SSTR2a staining suggests its need for the appropriate biotherapy.
1. 59%(all) and 69%(liver metastases) of NETs showed SSTR2a positivity which suggests the therapeutic response to SA and warrents SA as a first choice of biotherapy in SSTR2a positive cases.
2. In the selected cases of metastatic panreastic NEC in the liver, positive mTOR staining in both SSTR2a-positive and SSTR2a-negative cases may suggest the use of Everolimus as combined therapy with SA or monotherapy for metastatic diseases.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 44, Tuesday Afternoon