The aims of this study were to evaluate INSM1 expression in primary gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) and in their known metastases, in order to assess its sensitivity as compared with chromogranin-A (CgA) and synaptophysin (SYN), and to evaluate any change in expression between primary and metastatic disease.
Patients with pancreatic neuroendocrine tumors measuring ≤2cm, without distant metastases, were identified and categorized as Chromogranin A high (>420ng/mL) or Chromogranin A low (≤420ng/mL), and those lacking data on Chromogranin A levels were excluded from the study.
Age, stage, grade, peritoneal carcinomatosis and extra-abdominal metastases as well as serum chromogranin A and urine 5-HIAA concentrations at diagnosis did not correlate to drug sensitivity <i>ex vivo</i> SI-NETs exhibit intermediate sensitivity <i>ex vivo</i> to cytotoxic and targeted drugs.
In patients with NENs of the pancreas and NENs of the small intestine and caecum, increased CgA levels were associated with lymph node involvement, distant metastases and a baseline liver involvement.
Western blot identified chromogranin A-associated processing bands including vasostatin in small intestinal NENs as well as up-regulated expression of prohormone convertase in metastases.
In this study, the authors identified a panel of such markers that have been implicated in tumorigenicity, metastasis, and hormone production and hypothesized that transcript levels of the genes melanoma antigen family D2 (MAGE-D2), metastasis-associated 1 (MTA1), nucleosome assembly protein 1-like (NAP1L1), Ki-67 (a marker of proliferation), survivin, frizzled homolog 7 (FZD7), the Kiss1 metastasis suppressor (Kiss1), neuropilin 2 (NRP2), and chromogranin A (CgA) could be used to define primary SI NETs and to predict the development of metastases.
Cells from the nodal metastases were found to be immunoreactive for neuronspecific enolase, keratin intermediate filaments, and chromogranin A, but not for neurofilaments.