title: Melatonin Immunoreactivity in Malignant Small Intestinal Neuroendocrine Tumours.
abstract: OBJECTIVE
  Small intestinal neuroendocrine tumours (SI-NETs) are derived from enterochromaffin cells. After demonstrating melatonin in enterochromaffin cells, we hypothesized that SI-NETs may express and secrete melatonin, which may have an impact on clinical factors and treatment response.
  
  
  METHODS
  Tumour tissue from 26 patients with SI-NETs, representing paired sections of primary tumour and metastasis, were immunohistochemically stained for melatonin and its receptors, MT1 and MT2. Plasma melatonin and immunoreactivity (IR) for melatonin, MT1 and MT2 in tumour cells were compared to other tumour markers and clinical parameters. Melatonin was measured at two time points in fasting morning plasma from 43 patients with SI-NETs.
  
  
  RESULTS
  Melatonin IR was found in all SI-NETS. Melatonin IR intensity in primary tumours correlated inversely to proliferation index (p = 0.022) and patients reported less diarrhoea when melatonin IR was high (p = 0.012). MT1 IR was low or absent in tumours. MT2 expression was medium to high in primary tumours and generally reduced in metastases (p = 0.007). Plasma-melatonin ranged from 4.5 to 220.0 pg/L. Higher levels were associated with nausea at both time points (p = 0.027 and p = 0.006) and flush at the second sampling. In cases with disease stabilization or remission (n = 34), circulating melatonin levels were reduced in the second sample (p = 0.038).
  
  
  CONCLUSIONS
  Immunoreactive melatonin is present in SI-NETs. Circulating levels of melatonin in patients with SI-NETs are reduced after treatment. Our results are congruent with recent understanding of melatonin's endocrine and paracrine functions and SI-NETs may provide a model for further studies of melatonin function.
authors.affiliation: Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden.
authors.forename: Fanny
authors.initials: F
authors.lastname: Söderquist
authors.affiliation: Department of Medical Sciences, Section of Endocrine Oncology, Uppsala University, Uppsala, Sweden.
authors.forename: Eva Tiensuu
authors.initials: ET
authors.lastname: Janson
authors.affiliation: Department of Medical Sciences, Clinical Pharmacology and Osteoporosis, Uppsala University, Uppsala, Sweden.
authors.forename: Annica J
authors.initials: AJ
authors.lastname: Rasmusson
authors.affiliation: Department of Medical Sciences, Section of Endocrine Oncology, Uppsala University, Uppsala, Sweden.
authors.forename: Abir
authors.initials: A
authors.lastname: Ali
authors.affiliation: Department of Medical Sciences, Biochemical Endocrinology, Uppsala University, Uppsala, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Stridsberg
authors.affiliation: Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden.
authors.forename: Janet L
authors.initials: JL
authors.lastname: Cunningham
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007414:Intestinal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D007421:Intestine, Small / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D008297:Male; D008550:Melatonin / Q000097:blood / Q000378:metabolism*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018358:Neuroendocrine Tumors / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D044122:Receptor, Melatonin, MT1 / Q000378:metabolism*; D044123:Receptor, Melatonin, MT2 / Q000378:metabolism*; D044094:Receptors, Melatonin
chemical_list: D000970:Antineoplastic Agents; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D044094:Receptors, Melatonin; D008550:Melatonin