Alteration of the E-cadherin/?-catenin cell adhesion system is common in pulmonary neuroendocrine tumors and is an independent predictor of lymph node metastasis in atypical carcinoids

Abstract Background Pancreatic neuroendocrine tumors (pNETs) are a heterogeneous group of neoplasms with malignant behaviors that can develop from inert slow growth or low malignancy to aggressive metastasis during follow-up. Recently, vimentin and E-cadherin were shown to be prognostic markers in some malignant tumors but were not evaluated in pNETs. The aim of this study was to evaluate the expression and prognostic significance of vimentin and E-cadherin in grade 1 and 2 pNETs. Methods A retrospective review of 227 patients with grade 1 and 2 pNETs undergoing surgical resection was conducted. Tumor specimens were immunohistochemically stained for vimentin and E-cadherin. Correlations between vimentin and E-cadherin expression and other clinicopathological features were then analyzed. Furthermore, overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan-Meier and univariate and multivariate Cox regression methods. Results Among 227 patients, 55 (24.2%) harbored tumors with high vimentin expression, while 117 (51.5%) harbored tumors with loss of E-cadherin expression. Patients with high vimentin expression and loss of E-cadherin expression had significantly elevated risks of lymph node metastasis, distant metastasis, perineural invasion and an advanced American Joint Committee on Cancer (AJCC) stage compared with those with low vimentin expression and preserved E-cadherin expression, high vimentin expression and preserved E-cadherin expression, or low vimentin expression and loss of E-cadherin expression. Furthermore, multivariate analysis showed that high vimentin expression with loss of E-cadherin expression was an independent predictor of OS and DFS in patients with grade 1 and 2 pNETs who underwent resection (both P < 0.001). Conclusions The current study demonstrated that high vimentin expression with loss of E-cadherin expression was correlated with lymph node metastasis, distant metastasis, disease progression and a poor prognosis in patients with grade 1 and 2 pNETs who underwent resection.

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Faculty Opinions recommendation of Mesenteric tumor deposits in midgut small intestinal neuroendocrine tumors are a stronger indicator than lymph node metastasis for liver metastasis and poor prognosis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726786900.793528248 ◽

2017 ◽

Author(s):

Noam Harpaz ◽

Alexandros Polydorides

Keyword(s):

Lymph Node ◽

Liver Metastasis ◽

Lymph Node Metastasis ◽

Neuroendocrine Tumors ◽

Poor Prognosis ◽

Mesenteric Tumor ◽

Node Metastasis ◽

Small Intestinal

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Difficulty of predicting lymph node metastasis on CT in patients with rectal neuroendocrine tumors

PLoS ONE ◽

10.1371/journal.pone.0211675 ◽

2019 ◽

Vol 14 (2) ◽

pp. e0211675 ◽

Cited By ~ 6

Author(s):

Hajime Ushigome ◽

Yosuke Fukunaga ◽

Toshiya Nagasaki ◽

Takashi Akiyoshi ◽

Tsuyoshi Konishi ◽

...

Keyword(s):

Lymph Node ◽

Lymph Node Metastasis ◽

Neuroendocrine Tumors ◽

Node Metastasis

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High matrix metalloproteinase-to-E-cadherin ratio measured by bicolor fluorescent in situ hybridization is associated with lymphangiogenesis and lymph node metastasis in prostate cancer

Urologic Oncology Seminars and Original Investigations ◽

10.1016/j.urolonc.2010.05.001 ◽

2012 ◽

Vol 30 (3) ◽

pp. 306-313 ◽

Cited By ~ 1

Author(s):

Yi Luo ◽

Hitoshi Ohmori ◽

Kiyomu Fujii ◽

Yoshitomo Chihara ◽

Satoshi Maruyama ◽

...

Keyword(s):

Prostate Cancer ◽

In Situ Hybridization ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Matrix Metalloproteinase ◽

Fluorescent In Situ Hybridization ◽

Node Metastasis ◽

High Matrix ◽

E Cadherin

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Clinical significance of E-cadherin, β-catenin, vimentin and S100A4 expression in completely resected squamous cell lung carcinoma

Journal of Clinical Pathology ◽

10.1136/jclinpath-2013-201467 ◽

2013 ◽

Vol 66 (11) ◽

pp. 937-945 ◽

Cited By ~ 34

Author(s):

Hua Zhang ◽

Jun Liu ◽

Dongsheng Yue ◽

Liuwei Gao ◽

Daowei Wang ◽

...

Keyword(s):

Lymph Node ◽

Lymph Node Metastasis ◽

Prognostic Value ◽

Squamous Cell Lung Carcinoma ◽

Histological Differentiation ◽

Vimentin Expression ◽

Cell Lung Carcinoma ◽

Node Metastasis ◽

S100a4 Expression ◽

E Cadherin

ObjectiveThe aim of this study was to evaluate the prognostic value of E-cadherin, β-catenin, vimentin and S100A4 expression in a cohort of squamous cell lung carcinoma (SqCC) patients.MethodsTumours from 204 patients with surgically resected SqCC were used for the immunohistochemical analyses of E-cadherin, β-catenin, vimentin and S100A4 expression. Correlations between the expression of these markers and clinicopathological parameters were analysed using the χ2 test. The prognostic value of these markers was evaluated using univariate Kaplan–Meier survival analyses and multivariate Cox proportional hazards model analyses.ResultsSignificant associations between E-cadherin expression and T stage (p=0.040), histological differentiation (p=0.005), lymph node metastasis (p<0.001), and recurrence (p<0.001) were identified. Decreased β-catenin expression was significantly correlated with T stage (p=0.003) and lymph node metastasis (p=0.010). Vimentin expression was associated with histological differentiation (p=0.017) and lymph node metastasis (p=0.001). Moreover, significant correlations were observed between S100A4 expression and lymph node metastasis (p=0.020) and recurrence (p<0.001). In the univariate analyses, high E-cadherin expression was a positive indicator for overall survival (OS) (p<0.001) and disease-free survival (DFS) (p<0.001), whereas high S100A4 or vimentin expression were negative indicators for OS (p<0.001 and p=0.010, respectively) and DFS (p<0.001 and p=0.006, respectively). In the multivariate analyses, E-cadherin and S100A4 expression were independent prognostic factors for OS (HR 0.697, 95% CI 0.524 to 0.926, p=0.013, and HR 1.508, 95% CI 1.122 to 2.027, p=0.007, respectively) and DFS (HR 0.634, 95% CI 0.471 to 0.852, p=0.003, and HR 1.490, 95% CI 1.101 to 2.015, p=0.010, respectively).ConclusionsEffective analysis of E-cadherin and S100A4 expression may allow for the identification of patients who are at a high risk of recurrence and poor prognosis in SqCC.

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