SOX2 and Rb1 in esophageal small-cell carcinoma: their possible involvement in pathogenesis

Ishida, Hirotaka; Kasajima, Atsuko; Kamei, Takashi; Miura, Tsuyoshi; Oka, Naoki; Yazdani, Samaneh; Ozawa, Yohei; Fujishima, Fumiyoshi; Sakurada, Akira; Nakamura, Yasuhiro; Tanaka, Yoïchi; Kurosumi, Masafumi; Ishikawa, Yuichi; Okada, Yoshinori; Ohuchi, Noriaki; Sasano, Hironobu

doi:10.1038/modpathol.2016.222

Cited by 32 publications

(41 citation statements)

References 47 publications

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“…In 181 (74%) cases, the original pathology diagnosis provided from the contributing institutions was available. The same cohort was either partly or fully included in 2 previously published studies [20, 21], one that dealt with small-cell carcinoma of the esophagus in comparison to SCLC, and the other with PD-L1 expression and survival in lung NENs. Clinical and follow-up data were available in 227 (93%) and 226 patients (93%), respectively.…”

Section: Methodsmentioning

confidence: 99%

“…The mitotic count was evaluated in 2 mm 2 in the area showing the highest density of mitosis. Immunohistochemistry for synaptophysin, chromogranin A, CD56, TTF1, napsin A, CK5/6, p63, p40, and Ki67 was performed using previously described methods [20]. Synaptophysin, chromogranin A, and CD56 were assessed in a semiquantitative manner using a previously established scoring system (immunoreactive score, 0–12) [23].…”

Section: Methodsmentioning

confidence: 99%

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Clinicopathological Profiling of Lung Carcinoids with a Ki67 Index > 20%

et al. 2018

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The clinicopathological features of lung neuroendocrine neoplasms (NEN) with a high proliferative index at the border area between atypical carcinoid and neuroendocrine carcinoma have not been investigated so far. The aim of this study was, therefore, to search for lung NENs which are well differentiated but show Ki67 values that overlap with those of poorly differentiated (PD)-NENs. Resected lung NENs from 244 Japanese patients were reviewed, and Ki67 indices were assessed in all tumors. The data were then correlated to clinicopathological parameters and patient outcome. Among 59 (24%) well-differentiated (WD)-NENs and 185 (76%) lung PD-NENs, 7 were defined as WD-NENs with Ki67 indices > 20%. The Ki67 indices of these tumors (mean 29%, range 24–36) were significantly lower than those of PD-NENs (mean 74%, range 34–99). All WD-NENs with Ki67 > 20% lacked abnormal p53 and loss of retinoblastoma 1 (Rb1) expression. In contrast, many PD-NENs expressed p53 (48%) and showed loss of Rb1 (86%). The 2- and 5-year disease-free survival rates in WD-NEN patients with Ki67 > 20% were lower than those of WD-NEN patients with Ki67 ≤20% (p < 0.01 for disease-free and overall survival). No statistical differences were detected between outcome of WD-NEN patients with Ki67 > 20% and those of PD-NEN. It is concluded that WD-NEN patients with Ki67 > 20% share the morphological and immunohistochemical features of WD-NEN patients with Ki67 ≤20%, but they have a worse prognosis, suggesting that this tumor group requires particular attention in future classifications and probably new therapeutic regimes.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Clinicopathological Profiling of Lung Carcinoids with a Ki67 Index > 20%

et al. 2018

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“…A previous study demonstrated that abnormal expression of MAPK1 contributes to the occurrence of ESCA [35]. It has been reported that RB1 expression was downregulated in esophageal small-cell carcinoma [36]. CLTC is associated with endocytosis and mitosis in cancer cells [37].…”

Section: Discussionmentioning

confidence: 94%

A Novel Three-miRNA Signature Identified Using Bioinformatics Predicts Survival in Esophageal Carcinoma

Zhang

Dai

2020

BioMed Research International

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Objective. We identified differentially expressed microRNAs (DEMs) between esophageal carcinoma (ESCA) tissues and normal esophageal tissues. We then constructed a novel three-miRNA signature to predict the prognosis of ESCA patients using bioinformatics analysis. Materials and Methods. We combined two microarray profiling datasets from the Gene Expression Omnibus (GEO) database and RNA-seq datasets from the Cancer Genome Atlas (TCGA) database to analyze DEMs in ESCA. The clinical data from 168 ESCA patients were selected from the TCGA database to assess the prognostic role of the DEMs. The TargetScan, miRDB, miRWalk, and DIANA websites were used to predict the miRNA target genes. Functional enrichment analysis was conducted using the Database for Annotation, Visualization, and Integrated Discovery (David), and protein-protein interaction (PPI) networks were obtained using the Search Tool for the Retrieval of Interacting Genes database (STRING). Results. With cut-off criteria of P<0.05 and |log2FC| > 1.0, 33 overlapping DEMs, including 27 upregulated and 6 downregulated miRNAs, were identified from GEO microarray datasets and TCGA RNA-seq count datasets. The Kaplan–Meier survival analysis indicated that a three-miRNA signature (miR-1301-3p, miR-431-5p, and miR-769-5p) was significantly associated with the overall survival of ESCA patients. The results of univariate and multivariate Cox regression analysis showed that the three-miRNA signature was a potential prognostic factor in ESCA. Furthermore, the gene functional enrichment analysis revealed that the target genes of the three miRNAs participate in various cancer-related pathways, including viral carcinogenesis, forkhead box O (FoxO), vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (ErbB2), and mammalian target of rapamycin (mTOR) signaling pathways. In the PPI network, three target genes (MAPK1, RB1, and CLTC) with a high degree of connectivity were selected as hub genes. Conclusions. Our results revealed that a three-miRNA signature (miR-1301-3p, miR-431-5p, and miR-769-5p) is a potential novel prognostic biomarker for ESCA.

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“…However, the literature on the prevalence of CK18 expression is controversial for many cancers . For example, CK18 positivity has been described in 30% to 100% of oral squamous cell carcinomas (40,47), 0-100% of non-small cell lung cancers (44,46), and 0-43% of esophageal squamous cell carcinomas (18,45). These con icting data are likely to be caused by the use of different antibodies, immunostaining protocols, and criteria to determine CK18 positivity in these studies.…”

Section: Introductionmentioning

confidence: 94%

Diagnostic and Prognostic Impact of Cytokeratin 18 Expression in Human Tumors: A Tissue Microarray Study on 11,952 Tumors

Menz

Weitbrecht

Büscheck

et al. 2020

Preprint

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BackgroundCytokeratin 18 (CK18) is an intermediate filament protein of the cytokeratin acidic type I group and is primarily expressed in single-layered or “simple” epithelial tissues and carcinomas of different origin. MethodsTo systematically determine CK18 expression in normal and cancerous tissues, 11,952 tumor samples from 115 different tumor types and subtypes (including carcinomas, mesenchymal and biphasic tumors) as well as 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry in a tissue microarray format. ResultsCK18 was expressed in normal epithelial cells of most organs but absent in normal squamous epithelium. At least an occasional weak CK18 positivity was seen in 90 of 115 (78.3%) tumor types. Wide-spread CK18 positivity was seen in 37 (31.9%) of tumor entities, including adenocarcinomas of the lung, prostate, colon and pancreas as well as ovarian cancer. Tumor categories with variable CK18 immunostaining included cancer types arising from CK18 positive precursor cells but show CK18 downregulation in a fraction of cases, tumor types arising from CK18 negative precursor cells occasionally exhibiting CK18 neo-expression, tumors derived from normal tissues with variable CK18 expression, and tumors with a mixed differentiation. CK18 downregulation was for example seen in renal cell cancers and breast cancers, whereas CK18 neo-expression was found in squamous cell carcinomas of various origins. Down-regulation of CK18 in invasive breast carcinomas of no special type and clear cell renal cell carcinomas (ccRCC) was related to adverse tumor features in both tumors (p≤0.001) and poor patient prognosis in ccRCC (p=0.0088). Up-regulation of CK18 in squamous cell carcinomas was linked to high grade and lymph node metastasis (p<0.05). In summary, CK18 is consistently expressed in various epithelial cancers, especially adenocarcinomas. ConclusionsDown-regulation or loss of CK18 expression in cancers arising from CK18 positive tissues as well as CK18 neo-expression in cancers originating from CK18 negative tissues is linked to cancer progression and may reflect tumor dedifferentiation.

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SOX2 and Rb1 in esophageal small-cell carcinoma: their possible involvement in pathogenesis

Cited by 32 publications

References 47 publications

Clinicopathological Profiling of Lung Carcinoids with a Ki67 Index > 20%

Clinicopathological Profiling of Lung Carcinoids with a Ki67 Index > 20%

A Novel Three-miRNA Signature Identified Using Bioinformatics Predicts Survival in Esophageal Carcinoma

Diagnostic and Prognostic Impact of Cytokeratin 18 Expression in Human Tumors: A Tissue Microarray Study on 11,952 Tumors

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SOX2 and Rb1 in esophageal small-cell carcinoma: their possible involvement in pathogenesis

Cited by 32 publications

References 47 publications

Clinicopathological Profiling of Lung Carcinoids with a Ki67 Index &#x3e; 20%

Clinicopathological Profiling of Lung Carcinoids with a Ki67 Index &#x3e; 20%

A Novel Three-miRNA Signature Identified Using Bioinformatics Predicts Survival in Esophageal Carcinoma

Diagnostic and Prognostic Impact of Cytokeratin 18 Expression in Human Tumors: A Tissue Microarray Study on 11,952 Tumors

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Clinicopathological Profiling of Lung Carcinoids with a Ki67 Index > 20%

Clinicopathological Profiling of Lung Carcinoids with a Ki67 Index > 20%