Abstract
BackgroundChromogranin A (CgA), synaptophysin (Syn) and the Ki-67 index play significant roles in diagnosis or the evaluation of the proliferative activity of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). However, little is known about whether these biological markers change during tumor metastasis and whether such changes have effect on prognosis.MethodsWe analyzed 35 specimens of both primary and metastatic tumor from 779 patients who had been diagnosed as GEP-NENs at Wuhan Union Hospital from August 2011 to October 2019. The heterogeneity of CgA, Syn and Ki-67 index was evaluated by immunohistochemical analysis.ResultsAmong these 779 patients, the three most common sites of NENs in the digestive tract were the pancreas, rectum and stomach. Metastases were found in 311 (39.9%) patients. Among the 35 patients with both primary and metastatic pathological specimens, differences in the Ki-67 level were detected in 54.3% of the patients, while 37.1% showed a difference in CgA and only 11.4% showed a difference in Syn. Importantly, due to the difference in the Ki-67 index between primary and metastatic lesions, the WHO grade was changed in 8.6% of the patients. In addition, a Kaplan–Meier survival analysis showed that patients with Ki-67 index variation had a shorter overall survival (p = 0.0346), while neither Syn variation nor CgA variation was related to patient survival (p = 0.7194, p = 0.4829).ConclusionsOur data indicate that primary and metastatic sites of GEP-NENs may exhibit pathological heterogeneity. Ki-67 index variation is closely related to the poor prognosis of patients with tumor metastasis, but neither Syn variation nor CgA variation is related to patient prognosis. Therefore, clinicopathologic evaluation of the primary tumor and metastatic sites could be helpful for predicting the prognosis.
Highlights
Neuroendocrine neoplasms (NENs) are a group of rare and highly heterogeneous neoplasms originating from peptidergic neurons and neuroendocrine cells, which can exist in all parts of the body [1]
The grading system used in this study was based on the World Health Organization (WHO) 5th edition classification (2019) of digestive system tumors, in which NENs are classified as welldifferentiated neuroendocrine tumors (NETs), poorly differentiated neuroendocrine carcinomas (NECs), and mixed neuroendocrine–non-neuroendocrine neoplasm (MiNEN)
Pathological diagnosis showed that, among the 779 patients, NET-G1 accounted for 40.2%, NET-G2 18.5%, NET-G3 0.5%, NEC 34.7% and MiNEN 5.1%
Summary
Neuroendocrine neoplasms (NENs) are a group of rare and highly heterogeneous neoplasms originating from peptidergic neurons and neuroendocrine cells, which can exist in all parts of the body [1]. Chromogranin A (CgA) and synaptophysin (Syn) widely exist in neuroendocrine cells, and are currently necessary markers for the diagnosis of NENs [7, 8]. CgA was initially found in chromaffin particles of adrenal medulla containing catecholamines [9] It is a kind of acidic hydrophilic secreted protein found in the secretory vesicles of neuroendocrine cells [10]. CgA and the Ki-67 index play important roles in the diagnosis of NENs. little is known about whether these compounds change during tumor metastasis and whether such changes play a role in the overall process of metastasis. Chromogranin A (CgA), synaptophysin (Syn) and the Ki-67 index play significant roles in diagnosis or the evaluation of the proliferative activity of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Little is known about whether these biological markers change during tumor metastasis and whether such changes have effect on prognosis
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