Clinico-morphological analysis of the neuroendocrine neoplasms of the gastroenteropancreatic system.

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are unusual and rare epithelial tumors for which the diagnosis of the grade of malignancy and prognostic assessment on the basis ofhistology represent considerable challenges for the pathologist. In this study we conducted a retrospective analysis of the cell proliferation (Ki-67 nuclear antigen) in primary and metastatic GEP NENs of 137 patients as well as the assessment of keratin 19 (CKI9) and progesterone receptors (PR) expression in pancreatic NENs of 57 patients. In 19 (27,1%) GEP NEN metastases was found I,5-4,5-fold increase of Ki-67 index compared with their primaries. Consequently, 6 (21,4%) cases of NETGI and 4 (7,0%) cases of NET G2 were up-graded Pancreatic NETs G2 with Ki-67 index >5% were significantly associated with presence of distant metastases (p =0,007) and decreased survival (p=0,03). Decreased survival also was found in the group of gastrointestinal NET G2 with Ki-67 index > 15% (p=0,005). Further analysis of immunomorphological features and proliferative activity allowed to separate a rare group of tumors - ("NET G3", characterized by decreased survival comparing to NET G2. Expression of CKI9 in pancreatic NETs was significantly associated with higher proliferative activity of primary tumor (p =0,04) and adverse outcome (p=0,003). On other hand, PR expression correlated with lower Ki-67 index (p=0,006), absence of metastases (p=0,004) and favorable outcome (p=0,000). Our results show that Ki67 index is a key parameter of morphological diagnosis of GEP NENs. Thus, the studied markers are important parameters of the morphological diagnostic of GEP NENs, which allow more accurately assess the degree of malignancy, prognosis and treatment of the disease.