Prognostic factors in neuroendocrine carcinoma: biological markers are more useful than histomorphological markers

Abstract

Gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are a very aggressive type of cancer, for which prognostic factors are lacking. We analysed clinical and histomorphological prognostic markers of overall survival (OS), completed with a record of biological and haematological data of patients diagnosed between December 2002 and December 2015. The median OS was 16 months (95% CI 13.9–18.1). After univariate analysis, performance status (PS) ≥ 2 and stage IV were associated with a worse outcome (9 months and 14 months, respectively), as well as patients with lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) levels ≥ 2 ULN (9 months and 8 months, respectively). After multivariate analysis, LDH and AST levels were the only factors that remained significantly associated with better survival: HR 0.36 (p = 0.04) and 0.31 (p = 0.03), respectively. When patients had elevated LDH and AST levels, OS was 20 months, when they had high LDH or AST levels, 13 months and 8 months in the group with low LDH and AST levels (p < 0.001). Therefore, biological data appeared to be more relevant prognostic factors than usual factors described in other studies (PS, stage, and Ki-67). Considering LDH and AST levels at diagnosis could help physicians to predict survival and to stratify patients for clinical trials.

Prognostic significance of platelet-lymphocyte ratio in extrapulmonary neuroendocrine carcinoma

“…Some authors have reported that LDH and AST are independent factors representing poor prognosis in NEC [14][15][16]. Similarly, LDH was one of the impactful prognostic factors identi ed in this study.…”

“…However, AST was not a signi cant prognostic factor in this study. A previous study suggested a cut-off value of AST as 2 times the ULN [15], but there was only one patient with more than 2 times the ULN in this study. Therefore, to determine the prognostic signi cance of AST, a large number of patients with high AST levels should be included.…”

“…Similarly, LDH was one of the impactful prognostic factors identi ed in this study. The characteristics of NECs, such as high glucose consumption, high lactate production, a hypoxic tumor environment because of poor vascularization, and high proliferation, could increase LDH levels [15,17,18].…”

miR‐122‐5p promotes aggression and epithelial‐mesenchymal transition in triple‐negative breast cancer by suppressing charged multivesicular body protein 3 through mitogen‐activated protein kinase signaling

“…The forced expression of CHMP3 suppressed EMT program and MAPK signaling, suggesting that CHMP3 gene played an anticancer role in TNBC. Although, in human lung cancer and prostate cancer, CHMP3 gene has been reported to be expressed at a higher level, and its expression is associated with increased neuroendocrine differentiation of cancer cells (Walker, Antoniono, Ross, Paisley, & Oh, ; Wilson, Oh, Hwa, & Rosenfeld, ), which may predict poor prognosis (Chan et al, ; Freis et al, ; Terry & Beltran, ). 25.1 protein encoded by CHMP3 gene was found upregulated in M12 prostate cancer cells and non‐small‐cell lung cancer with neuroendocrine differentiation (Walker et al, ).…”

P53, Somatostatin receptor 2a and Chromogranin A immunostaining as prognostic markers in high grade gastroenteropancreatic neuroendocrine neoplasms

“…Patients with GEP-NEN with a Ki67-index > 20% diagnosed between the 1st of January 2012 and 31st of December 2016 and referred to the ENETS Neuroendocrine Tumour Centre of Excellence, Rigshospitalet were included. Patients with neuroendocrine cancer of unknown primary (CUP) predominantly with abdominal metastases were also included, in agreement with several prior publications [6,10,[15][16][17][18][19][20].…”