Background: Primary small cell carcinoma (SCC) of the esophagus is a rare and aggressive tumor with poor prognosis. In this study, we report the clinicopathological characteristics of 21 cases of small cell carcinoma of the esophagus treated at the Cancer Center of Sun Yat-Sen University, with particular focus on the histologic and immunohistochemical findings.

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The serine ⁄ threonine kinase UNC-51-like kinase 1 (ULK1) plays an essential role in autophagosome formation, although the exact molecular mechanism is unknown. The present study was first to investigate the clinical and prognostic significance of ULK1 in esophageal squamous cell carcinoma (ESCC). Protein and mRNA levels of ULK1 in normal esophageal epithelial cells, ESCC cell lines, paired ESCC lesions and the adjacent noncancerous tissues were examined using western blot and real-time RT-PCR. The results showed that only the ULK1 protein level was upregulated in ESCC samples compared with normal esophageal cells and tissues. Also, we found that protein stabilization of ULK1 was higher in ESCC cell lines. Furthermore, immunohistochemical staining of ULK1 was performed on the tissue microarray containing 248 ESCC and 51 normal esophageal tissues. A total of 70.2% ESCC specimens showed intensive expression of ULK1 in contrast to the undetectable expression of ULK1 in normal esophageal tissues. Statistical analysis revealed that ULK1 expression was significantly correlated with T status (P = 0.048). Moreover, patients with higher ULK1 expression were associated with shorter overall survival time. Multivariate analysis suggested that ULK1 expression and N status (P < 0.001) were independent prognostic indicators for the survival of patients. Functional studies showed that suppression of ULK1 expression in ESCC cell lines by specific small interfering RNA resulted in inhibition of cell proliferation and induction of apoptosis under starvation conditions. These findings provide evidence that ULK1 represents a novel and clinically useful biomarker for ESCC patients and plays an important role during the progression of ESCC. (Cancer Sci 2011; 102: 1568-1575 E sophageal carcinoma has been reported as the eighth most occurring cancer and the sixth leading cause of cancer death in the world.(1,2) Esophageal squamous cell carcinoma (ESCC) is the predominant histological subtype of esophageal carcinoma in Asia, (3) especially in north central China.(4) Great advances have been achieved in surgical techniques and perioperative management in recent years; however, the mortality of this disease has not been significantly decreased. The main reason for poor prognosis of ESCC is that most early cases are asymptomatic, therefore patients are usually diagnosed at an advanced stage when the cancer has displayed local invasion and lymph node metastasis. Currently, only the stage based on the tumornode-metastasis (TNM) classification is widely accepted as a prognostic factor, which is not as precise as desired. Therefore, there is urgency to identify sensitive and specific biological markers that could accurately evaluate the prognosis of ESCC clinically.Macroautophagy (herein referred to as autophagy) is a dynamic process that intracellular double-membrane structures called autophagosomes sequester cytoplasmic contents, then fuse with lysosomes for breakdown and turn over these metabolic materials. (5,6) In normal cells, autophagy h...

BackgroundTumor Protein p53 (p53), cyclin-dependent kinase inhibitor 1A (p21/WAF1), and murine double minute 2 (MDM2) participate in the regulation of cell growth. Altered expression of these gene products has been found in malignant tumors and has been associated with poor prognosis. Our aim was to investigate the expression of the 3 proteins in hepatocellular carcinoma (HCC) and their prognostic significance.MethodsWe examined p53, p21/WAF1, and MDM2 expression in 181 pairs of HCC tissues and the adjacent hepatic tissues by performing immunohistochemistry and examined the expression of the 3 proteins in 7 pairs of HCC tissues and the adjacent hepatic tissues by using western blot analysis.ResultsThe expression of p53, p21/WAF1, and MDM2 in the HCC tissues was significantly higher than those in the adjacent hepatic tissues (P < 0.05). A statistical correlation was observed between p53 and p21/WAF1 expression in HCC tissues (R = 0.195, P = 0.008). A statistical correlation was observed between expression of p53 and p21/WAF1 (R = 0.380, P = 0.000), p53 and MDM2 (R = 0.299, P = 0.000), p21/WAF1 and MDM2 (R = 0.285, P = 0.000) in 181 liver tissues adjacent to the tumor. Patients with a low pathologic grade HCC (I+II) had a higher tendency to express p53 on tumor cells than the patients with high pathologic grade HCC (III+IV) (P = 0.007). Survival analysis showed that positive p21/WAF1 expression or/and negative MDM2 expression in HCC was a predictor of better survival of patients after tumor resection (P < 0.05).ConclusionsThe proteins p53, p21/WAF1, and MDM2 were overexpressed in all the HCC cases in this study, and p53 and p21/WAF1 overexpression were positively correlated. The expression of p21/WAF1 and MDM2 can be considered as 2 useful indicators for predicting the prognosis of HCC.

Deregulation of alternative splicing contributes to the malignant progression of cancer. Little is known about the significant alternative splicing events in hepatocellular carcinoma (HCC). High through-put sequencing revealed that CCDC50 pre-mRNA is aberrantly spliced in 50% of our HCC cases. A BaseScope assay was performed to examine the expression of CCDC50S (a truncated oncogenic splice variant) in HCC tissues. Compared with liver benign tumors and several types of solid tumors, CCDC50S mRNA was up-regulated in HCC, with a diagnostic potential (sensitivity: 0.711, specificity: 0.793). High expression of CCDC50S mRNA in HCC was significantly correlated with poor tumor differentiation, advanced TNM stage and unfavorable prognosis. Overexpression of CCDC50S exerted tumorigenic activities that promoted HCC growth and metastasis via activation of Ras/Foxo4 signaling. Either suppression of MEK/ERK phosphorylation or overexpression of Foxo4 markedly attenuated CCDC50S-mediated phenotypes. Furthermore, serine and arginine rich splicing factor 3 (SRSF3) directly bound to CCDC50S mRNA to maintain its stability in the cytoplasm. The cytosolic retention of SRSF3 was mediated by the interaction of HBx and 14-3-3β. Ectopic HBx expression induced the expression of cytosolic SRSF3 and CCDC50S. Our study provided compelling evidence that up-regulation of CCDC50S was modulated by HBx/SRSF3/14-3-3β complex, and enhanced the oncogenic progression of HCC via the Ras/Foxo4 signaling pathway. These data suggest that CCDC50S may serve as a novel diagnostic and prognostic biomarker, and probably a promising therapeutic target in HCC. This article is protected by copyright. All rights reserved.