Olfactory receptor 51E1 as a novel target for diagnosis in somatostatin receptor-negative lung carcinoids

    1. Apostolos V Tsolakis2
    1. 1Department of Medical Sciences, Endocrine Oncology, Science for Life Laboratory, Uppsala University Hospital, Uppsala University, Entrance 70, 3rd Floor, Research Department 2, SE-751 85 Uppsala, Sweden
      2Department of Medical Sciences, Endocrine Oncology
      3Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
      4Centre of Excellence for Endocrine Tumors, Uppsala University Hospital, Uppsala, Sweden
      5Division of Pathology and Laboratory Medicine, European Institute of Oncology, Milan, Italy
      6Department of Biomedical and Clinical Sciences ‘Luigi Sacco’, University of Milan School of Medicine, Milan, Italy
    1. Correspondence should be addressed to A V Tsolakis; Email: apostolos.tsolakis{at}medsci.uu.se


    Somatostatin receptors (SSTRs) may be used in lung carcinoids (LCs) for diagnosis and therapy, although additional targets are clearly warranted. This study aimed to investigate whether olfactory receptor 51E1 (OR51E1) may be a potential target for LCs. OR51E1 coding sequence was analyzed in LC cell lines, NCI-H727 and NCI-H720. OR51E1 transcript expression was investigated in LC cell lines and frozen specimens by quantitative real-time PCR. OR51E1, SSTR2, SSTR3, and SSTR5 expression was evaluated by immunohistochemistry on paraffin-embedded sections of 73 typical carcinoids (TCs), 14 atypical carcinoids (ACs), and 11 regional/distant metastases and compared with OctreoScan data. Immunohistochemistry results were rendered semiquantitatively on a scale from 0 to 3, taking into account the cellular compartmentalization (membrane vs cytoplasm) and the percentage of tumor cells (<50 vs >50%). Our results showed that WT OR51E1 transcript was expressed in both LC cell lines. OR51E1 mRNA was expressed in 9 out of 12 TCs and 7 out of 9 ACs (P=NS). Immunohistochemically, OR51E1, SSTR2, SSTR3, and SSTR5 were detected in 85, 71, 25, and 39% of TCs and in 86, 79, 43, and 36% of ACs respectively. OR51E1 immunohistochemical scores were higher or equal than those of SSTRs' in 79% of TCs and 86% of ACs. Furthermore, in the LC cases where all SSTR subtypes were lacking, membrane OR51E1 expression was detected in 10 out of 17 TCs and 1 out of 2 ACs. Moreover, higher OR51E1 immunohistochemical scores were detected in 5 out of 6 OctreoScan-negative LC lesions. Therefore, the high expression of OR51E1 in LCs makes it a potential novel diagnostic target in SSTR-negative tumors.

    • Revision received 13 August 2013
    • Accepted 22 August 2013
    • Made available online as an Accepted Preprint 22 August 2013
    | Table of Contents