High FDG uptake on PET is associated with negative cell-to-cell adhesion molecule E-cadherin expression in lung adenocarcinoma

Higashi, Kõtarõ; Ueda, Yoshimichi; Shimasaki, Miyako; Ishigaki, Yasuhito; Nakamura, Yuka; Oguchi, Manabu; Takegami, Tsutomu; Watanabe, Naoto

doi:10.1007/s12149-017-1187-y

Cited by 13 publications

(11 citation statements)

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“…Epithelial cell migration requires the dissociation of cell-cell contacts, which are regulated by homotypic interactions between E-cadherin from adjacent cells [ 9 ]. Deregulation of E-cadherin expression and its function in invasion and metastasis has been demonstrated in small cell lung cancer [ 21 ], breast cancer [ 22 ], colon cancer [ 23 ] and cervical cancer [ 24 ]. In human colon cancer cells transfected to express HPV-16 E6 and E7 oncoproteins, E-cadherin expression is reduced, mainly through E6 protein [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Ezrin and E-cadherin expression profile in cervical cytology: a prognostic marker for tumor progression in cervical cancer

et al. 2018

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BackgroundCervical cancer (CC) is the fourth cause of mortality by neoplasia in women worldwide. The use of immunomarkers is an alternative tool to complement currently used algorithms for detection of cancer, and to improve selection of therapeutic schemes. Aberrant expression of Ezrin and E-cadherin play an important role in tumor invasion. In this study we analyzed Ezrin and E-cadherin expression in liquid-based cervical cytology samples, and evaluated their potential use as prognostic immunomarkers.MethodsImmunocytochemical staining of Ezrin and E-cadherin was performed in cervical samples of 125 patients. The cytological or histological diagnostic was performed by Papanicolaou staining or H&E staining, respectively. HPV genotyping was determined using INNO-LIPA Genotyping Extra kit and the HPV physical status by in situ hybridization. Ezrin expression in HaCaT, HeLa and SiHa cell lines was determined by immunocytochemistry, immunofluorescence and Western blot.ResultsHigh Ezrin expression was observed in cervical cancer samples (70%), samples with multiple infection by HR-HPV (43%), and samples with integrated viral genome (47%). High Ezrin expression was associated with degree of SIL, viral genotype and physical status. In contrast, low E-cadherin expression was found in cervical cancer samples (95%), samples with multiple infection by HR-HPV/LR-HPV (87%) and integrated viral genome (72%). Low E-cadherin expression was associated with degree of SIL and viral genotype. Interestingly, Ezrin nuclear staining was associated with degree of SIL and viral genotype. High Ezrin expression, high percent of nuclear Ezrin and low E-cadherin expression behaved as risk factors for progression to HSIL and cervical cancer.ConclusionsEzrin and E-cadherin expression profile in cervical cytology samples could be a potential prognostic marker, useful for identifying cervical lesions with a high-risk of progression to cervical cancer.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4243-7) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Ezrin and E-cadherin expression profile in cervical cytology: a prognostic marker for tumor progression in cervical cancer

et al. 2018

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“…Phase 3 trials comparing lung lobectomy versus segmentectomy for lung cancers 2 cm with C/T ratios > 0.5 are in progress. 38,39 There is an association between 18 F-fludeoxyglucose uptake on PET and the EMT in NSCLC, 40,41 which was not observed here. The reason may be that both studies analyzed patients with advanced stages of disease and that we were unable to accumulate PET data from all cases in our cohort.…”

Section: Discussionmentioning

confidence: 51%

“…The institutional review board of Kyushu University approved our study (No. [30][31][32][33][34][35][36][37][38][39][40][41].…”

Section: Patientsmentioning

confidence: 99%

Clinical and Prognostic Significance of the Epithelial–Mesenchymal Transition in Stage IA Lung Adenocarcinoma: A Propensity Score–Matched Analysis

Matsubara

Tagawa

Takada

et al. 2019

Clinical Lung Cancer

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We aimed to analyze the clinical significance of the epithelialemesenchymal transition (EMT) in stage IA lung adenocarcinoma. Tumors with the EMT phenotype were identified in 43.1% of patients with a high ratio of consolidation to tumor diameter. Propensity score matching indicated a significant association of the EMT with shorter survival. Background: The epithelialemesenchymal transition (EMT) describes the process through which cells lose epithelial characteristics and gain a mesenchymal phenotype. The EMT contributes to tumor invasion and cancer progression, and is associated with metastasis and poor survival of patients with nonesmall-cell lung cancer. However, little is known about the relationships between the EMT and the clinicopathologic characteristics of patients with stage IA lung adenocarcinoma. Patients and Methods: We conducted immunohistochemical analysis of the expression of the EMT markers E-cadherin and vimentin of specimens acquired from 183 consecutive patients with stage IA lung adenocarcinoma. The clinicopathologic significance of the association of the EMT status with E-cadherin and vimentin expression was analyzed after propensity score matching. Results: E-cadherin and vimentin were detected in 68.3% and 18.6% of stage IA lung adenocarcinomas, respectively. The presence of cells with EMT conversion was associated with older patient age. A propensity scoreematched cohort (128 patients) was used for further analyses. Computed tomography revealed that tumors with EMT conversion showed solid-dominant nodules compared to those without conversion. Survival analysis after propensity score matching showed that the EMT correlated with poor disease-free survival (hazard ratio ¼ 2.57, P ¼ .0451) and overall survival (hazard ratio ¼ 4.23, P ¼ .0471). Multivariate analysis revealed that the EMT was an independent predictor of shorter disease-free survival. Conclusion: The EMT was a significant predictor of poor prognosis of patients with stage IA lung adenocarcinoma. The EMT status may serve as an indicator for administering adjuvant therapy.

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“…42,43 Conversely, PD-L1 expression has been reported to be downregulated by EMT induction, and the high 18 F-FDG-uptake in cancer tissues is negatively related to low E-cadherin expression as one of the EMT phenotypes. 23 Interestingly, the HIF-1A/GLUT1/ EMT axis has been known to regulate PD-L1 expression as well as 18 F-FDG-uptake; 22,28 however, the relationship between PD-L1 expression, FDG-uptake, and the HIF-1A/GLUT1/EMT axis in identical OSCC samples has not yet been investigated. In this study, we could clarify the significant opposite correlation of high 18 F-FDG-uptake and low PD-L1 expression with respect to the activation of the HIF-1A/GLUT1/EMT axis in patients with OSCC for the first time.…”

Section: Discussionmentioning

confidence: 99%

“…22 Furthermore, there are also reports on the relationship between epithelial-mesenchymal transition (EMT) and 18 F-FDG-uptake. 23 However, to date, information regarding the clinicopathological significance, tumour immune status and the non-invasive assessment of 18 F-FDG-uptake, which was regulated by the accumulation of HIF-1A and GLUT1 and EMT induction characterised by the epithelial marker suppression in OSCC, remains limited. Remarkably, the HIF-1A/GLUT1/EMT axis correlates with not only the cold tumour immune status but also chemoradiation therapy, cancer aggressiveness and poor prognosis.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic value of 18F-FDG-PET to predict the tumour immune status defined by tumoural PD-L1 and CD8+tumour-infiltrating lymphocytes in oral squamous cell carcinoma

et al. 2020

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BACKGROUND: Lately, immune checkpoint proteins, such as programmed death 1 (PD-1) and its ligand-1 (PD-L1), have garnered attention as a new target in oral squamous cell carcinoma (OSCC). Reportedly, fluoro-D-glucose (FDG)-uptake alteration by anti-PD-1 antibody treatment depicts the response in patients with lung cancer. This study aims to elucidate the correlations between tumour immune status, clinicopathological factors, 18 F-FDG-uptake and cold tumour phenotypes as low PD-L1 expression/low CD8 + tumour-infiltrating lymphocytes (TILs) in OSCC. METHODS: We performed immunohistochemical analysis of PD-L1, hypoxia-inducible factor 1 A (HIF-1A), glucose transporter type 1 (GLUT1), CD8, E-cadherin and Ki-67 on 59 operable OSCC samples. We assessed the correlations between these factors and preoperative 18 F-FDG-uptake, clinicopathological characteristics and prognosis. RESULTS: Low expression of PD-L1 in OSCC correlated with cancer aggressiveness, poor prognosis, high 18 F-FDG-uptake with HIF-1A/GLUT1 and low E-cadherin expression and low CD8. Cold tumour phenotypes as low PD-L1 tumour cells and low stromal CD8 correlated with the poor prognosis, high 18 F-FDG-uptake and E-cadherin suppression. Furthermore, the high level of preoperative 18 F-FDG-uptake in OSCC was an independent predictor of the cold tumour immune status. CONCLUSIONS: 18 F-FDG-uptake is an independent predictor of cold tumour in OSCC. 18 F-FDG-PET imaging could be a promising diagnostic tool to estimate tumour immune status.

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High FDG uptake on PET is associated with negative cell-to-cell adhesion molecule E-cadherin expression in lung adenocarcinoma

Cited by 13 publications

References 14 publications

Ezrin and E-cadherin expression profile in cervical cytology: a prognostic marker for tumor progression in cervical cancer

Ezrin and E-cadherin expression profile in cervical cytology: a prognostic marker for tumor progression in cervical cancer

Clinical and Prognostic Significance of the Epithelial–Mesenchymal Transition in Stage IA Lung Adenocarcinoma: A Propensity Score–Matched Analysis

Diagnostic value of 18F-FDG-PET to predict the tumour immune status defined by tumoural PD-L1 and CD8+tumour-infiltrating lymphocytes in oral squamous cell carcinoma

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