Abstract
BackgroundThe worldwide incidence of neuroendocrine tumors (NETs) has increased remarkably, with the hindgut being the second most common site for such tumors. However, the mechanisms underlying progression and metastasis of hindgut NETs are unclear. A retrospective study was conducted to elucidate these mechanisms.MethodsClinicopathological data of cases of hindgut NET between April 1996 and September 2015 were analyzed, retrospectively. Patients with neuroendocrine carcinoma were excluded. Formalin-fixed paraffin-embedded tissues of hindgut NET cases were subjected to detailed morphometric and immunohistochemical analyses. Statistical analyses were performed using the non-parametric Mann-Whitney U test, Spearman’s correlation coefficient, and chi-squared test. Multivariate logistic regression analysis was conducted as appropriate for the data set.ResultsFifty-six hindgut NET cases were considered. Microvessel density and lymphatic microvessel density were identified as significant risk factors for venous and lymphatic invasion. There was a positive correlation between microvessel density and the maximum tumor diameter. Multivariate logistic regression analysis revealed that the maximum tumor diameter alone was an independent predictor of lymph node metastasis, whereas lymphovascular invasion and MVD was not the predictor of lymph node metastasis. There were no significant correlations between the Ki-67 labeling index and any of the parameters evaluated including age, sex, the maximum tumor diameter, venous invasion, lymphatic invasion, microvessel density, lymphatic microvessel density, and lymph node metastasis.ConclusionsAngiogenic mechanisms may play important roles in the progression of hindgut NET. Otherwise, the maximum tumor diameter alone was an independent predictor of lymph node metastasis in hindgut NETs. Moreover, our study raises the question of whether the presence of lymphovascular invasion, in endoscopically obtained hindgut NET tissues, is an absolute indication for additional surgery or not.
Highlights
The worldwide incidence of neuroendocrine tumors (NETs) has increased remarkably, with the hindgut being the second most common site for such tumors
To elucidate hidden risk factors for hindgut NETs, we previously conducted a pathological study using endoscopically resected specimens of hindgut NET and proposed that angiogenesis plays an important role in the initial phase of this tumor [4]
Data from patients with neuroendocrine carcinoma (NEC) were excluded because: (i) the clinical management of NEC is different [9], and (ii) studies have shown that colorectal NEC and hindgut adenocarcinoma have a similar mutation profile that differs from that of NET G1-G2 [10, 11]
Summary
The worldwide incidence of neuroendocrine tumors (NETs) has increased remarkably, with the hindgut being the second most common site for such tumors. The World Health Organization (WHO) grading system for GEP-NETs was updated in 2010 [4] This grading system is based on the proliferative activities of tumor cells (mitotic counts and Ki-67 labeling index). Hindgut NET cases with relatively low levels of proliferative activities may have discordant tumor progression, invasion, Okubo et al BMC Cancer (2017) 17:769 metastasis, and/or overall prognosis [4, 7, 8]. To elucidate hidden risk factors for hindgut NETs, we previously conducted a pathological study using endoscopically resected specimens of hindgut NET and proposed that angiogenesis plays an important role in the initial phase (occurrence and progression) of this tumor [4]. To obtain a more detailed and accurate assessment of the mechanisms of hindgut NET progression and metastasis, we sampled a greater number of patients, including those who had undergone surgery
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
