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
  1. Figure 1

    OR51E1 transcript expression in established human neuroendocrine tumor cells. OR51E1 expression was evaluated by QRT-PCR and normalized to β-actin (set as 1). s.d.s of triplicate samples are shown. NCI-H727, typical lung carcinoid; NCI-H720, atypical lung carcinoid; KRJ-1 and CNDT2.5, small intestine neuroendocrine carcinomas. LNCaP cells, from a prostate carcinoma, were used as a positive control and 1064SK cells, from normal skin fibroblast, were used as a negative control.

  2. Figure 2

    OR51E1 immunostaining in lung carcinoids. Immunostaining patterns in the neoplastic cells of typical carcinoids are illustrated as non-immunoreactive, score 0 (A); pure cytoplasmic, score 1 (B); incomplete membranous in <50% of tumor cells, score 2 (C); and circumferential membranous in >50% of tumor cells, score 3 (D). Representative immunostaining in lymph node metastasis, score 3, from a typical carcinoid (E), and in liver metastasis, score 2, from an atypical carcinoid (F), are also shown. Neutralized immunostaining in the same cell clusters is shown in each inset. Bar=50 μm.

  3. Figure 3

    Summary of SSTR2, SSTR3, SSTR5, and OR51E1 immunohistochemical scores in primary typical (A) and atypical carcinoids (B). X-axis shows score 0 (S0) to S3, whereas y-axis shows the percentage of analyzed tumors (indicated above the columns), which were immunostained for each receptor and classified in each scoring category. The number of tumors that correlates with each percentage, in 72 primary typical carcinoids, is S0: 21, 54, 44, 11 vs S1: 9, 14, 23, 1 vs S2: 17, 4, 5, 28 vs S3: 25, 0, 0, 32 for SSTR2, SSTR3, SSTR5, and OR51E1 respectively and, in 14 primary atypical carcinoids, is S0: 3, 8, 9, 2 vs S1: 2, 5, 5, 0 vs S2: 6, 1, 0, 3 vs S3: 3, 0, 0, 9 for SSTR2, SSTR3, SSTR5, and OR51E1 respectively. All the numerical values as described above represent calculations based on the median immunohistochemical scores obtained by the three investigators, whereas the ranges of the scores are indicated by the error bars for each column.

  4. Figure 4

    Representative immunostaining with higher OR51E1 score compared with SSTR2, SSTR3, and SSTR5 in a primary typical carcinoid. OR51E1 shows membrane pattern staining in the tumor cells (score 3). The inset highlights OR51E1 membranous staining with a higher magnification (×800), of the tumor cells marked by the red frame. SSTR2 (photo obtained from immunostaining by using anti-SSTR2, clone UMB1) and SSTR3 exhibit mainly cytoplasmic staining in these tumor cells (score 1), for which neutralized immunostaining are shown in the insets. The tumor is non-immunoreactive for SSTR5 (score 0). Bar=50 μm.

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