[Expression and biological significance of HPA and HIF-1alpha in human esophageal squamous cell carcinoma].

To investigate the expression of HPA and HIF-1alpha in human esophageal squamous cell carcinoma and their relationship with cancer development, invasion and metastasis. The expression of HPA mRNA and HIF-1alpha protein in 23 mucosa specimens of incisal margin, 26 para-tumorous dysplastic tissues and 70 esophageal squamous cell carcinoma specimens were detected by in situ hybridization assay and immunohistochemical staining, respectively. The positive expression of HPA mRNA and HIF-1alpha protein were significantly increased as the epithelial cells progressed into carcinoma (P < 0.05). The expression of HPA mRNA and HIF-1alpha protein in the esophageal squamous cell carcinoma were significantly correlated with the invasion depth, lymph node metastasis and clinical staging (P < 0.05), while it was not correlated with the differentiation of tumors (P > 0.05). There was a close correlation between the expression of HPA mRNA and HIF-1alpha protein in the carcinoma tissues (P < 0.01). The high expression of HPA mRNA and HIF-1alpha protein is correlated with carcinogenesis, progression, invasion and metastasis of esophageal squamous cell carcinoma. There may be a positive cooperation between two of them in the carcinogenesis and development of esophageal carcinoma. The determination of HPA mRNA and HIF-1 alpha will be useful in predicting tumor biological behavior.

Liu JL ，Zhou BJ ，Zhang Y ，Wu YP ，Liu SZ ，G A O WM ，Xue J ，Liu WH ... -  《-》

[Expression of hypoxia-inducible factor-1alpha and vessel endothelial growth factor in esophageal squamous cell carcinoma and clinico-pathological significance thereof].

To investigate the expression of hypoxia-inducible factor (HIF)-1alpha and vessel endothelial growth factor (VEGF) and their relations with the clinicopathological features of esophageal squamous cancer. Esophageal squamous cancer tissues and normal end squamous epithelium tissues were collected from 42 patients during operation. Real-time quantitative PCR was used to detect the mRNA expression of HIF-1alpha and VEGF and immunohistochemistry was used to detect the protein expression of HIF-1alpha and VEGF. The relations between the expression of HIF-1alpha, VEGF and depth of tumor invasion, histological grade, lymphatic invasion, and lymph node metastasis were evaluated. The HIF-1alpha mRNA expression level was 5.88 + 1.12 in the esophageal squamous cancer tissue, higher, but not significantly, than that in normal end squamous epithelium tissue 4.76 +/- 1.26 (P = 0.014). The VEGF mRNA expression level in the esophageal squamous cancer tissue was 12.79 +/- 2.51, higher, but not significantly, than that in the normal end squamous epithelium tissue (10.92 +/- 2.23, P = 0.010). The HIF-1alpha and VEGF protein positive rates in esophageal squamous cancer tissue were 50% (21/42) and 76% (32/42) respectively, significantly higher than those in the normal esophageal tissue [14% (6/42) and 33% (14/42) respectively, P = 0.001, P = 0.000]. The expression of HIF-1alpha mRNA and VEGF mRNA in the esophageal squamous cancer were correlated with lymph node metastasis (including lymphatic invasion) (P = 0.063 and P = 0.073 respectively). HIF-1alpha immunoreactivity was localized in the nucleus and/or cytoplasm of the cancer cells. The expression of HIF-1alpha protein was correlated with lymph node metastasis and histological grade (P = 0.013 and P = 0.028 respectively). No correlation was found between HIF-1alpha mRNA and VEGF protein. HIF-1alpha may be regulated at transcription and post-transcription levels in addition to protein level. It also plays an important role in lymphatic metastasis of esophageal squamous cancer and tumor malignancy degree. So HIF-1alpha and VEGF may serve as predictors of progression in esophageal squamous cell carcinoma and as potential targets for anti-angiogenesis therapy of esophageal squamous cell carcinoma.

Yu ZT ，Zhao HF ，Shang XB 《-》

Correlation of hypoxia inducible factor-1alpha with lymphatic metastasis via vascular endothelial growth factor-C in human esophageal cancer.

Hypoxia inducible factor (HIF)-1alpha is a transcription factor that regulates the transcription of genes associated with cell proliferation and vascular development. In various cancer tissues, HIF-1alpha is associated with clinicopathological factors, such as the tumor size, histological grade, and lymph node status. Although HIF-1alpha plays a critical role in tumor growth by inducing vascular endothelial growth factor (VEGF), it is unclarified whether HIF-1alpha affects lymphatic metastasis. The purpose of this study is to clarify the correlation of HIF-1alpha protein expression with lymph node metastasis in esophageal squamous cell carcinoma (ESCC). The expressions of HIF-1alpha and VEGF-C, which is one of the main lymphangiogenic factors, were examined in five ESCC cell lines and 48 surgical specimens of ESCC. HIF-1alpha and VEGF-C mRNAs were expressed in all the five ESCC cell lines as determined by RT-PCR analysis. Immunohistochemically, 34 of the 48 patients (70.8%) were positive for HIF-1alpha and 29 patients (60.4%) were positive for VEGF-C. Clinicopathologically, HIF-1alpha expression correlated with lymphatic invasion and VEGF-C expression (P = 0.003 and P = 0.01, respectively). Furthermore, HIF-1alpha expression tended to correlate with lymph node metastasis (P = 0.09). These findings suggest that HIF-1alpha plays a role in lymphatic invasion and lymph node metastasis through the induction of VEGF-C in ESCC.

Katsuta M ，Miyashita M ，Makino H ，Nomura T ，Shinji S ，Yamashita K ，Tajiri T ，Kudo M ，Ishiwata T ，Naito Z ... -  《EXPERIMENTAL AND MOLECULAR PATHOLOGY》

[Expression of nucleostemin mRNA and protein in the esophageal squamous cell carcinoma].

To investigate the mRNA and protein expression of nucleostemin (NS) in human esophageal squamous cell carcinoma. The mRNA and protein expression of NS were detected in 31 mucosal atypical hyperplasia specimens, 62 esophageal squamous cell carcinoma specimens and the matched normal esophageal mucosa samples by RT-PCR and immunohistochemistry method, respectively. The positive expression rate of NS protein in normal esophageal mucosa, atypical hyperplasia and esophageal squamous cell carcinoma was 17.7% (11/62), 41.9% (13/31) and 69.4% (43/62), respectively. There was a significant difference among the above three groups (chi2 = 33.676, P < 0.01). The expression levels of NS mRNA in esophageal squamous cell carcinoma (0.971 +/- 0.121) was significantly higher than that in the atypical hyperplasia (0.913 +/- 0.085) and also in the normal esophageal mucosa (0.866 +/- 0.103; F = 14.829, P < 0.01). The expression level of both NS protein and mRNA was positively correlated with histological grade, infiltration depth, and lymph node metastasis (P < 0.05), but not with age, gender or pathological type (P > 0.05). Our results indicate that nucleostemin mRNA and protein are over-expressed in human esophageal squamous cell carcinoma, and it may be related with its oncogenesis.

Zhang GY ，Yin L ，Li SL ，Xing WY ，Zhao QM ，Le XP ，Gao DL ，Chen KS ，Zhang YH ，Zhang QX ... -  《-》

[Relationship between the expression of hypoxia-inducible factor-1alpha and chemotherapy response in esophageal squamous cell carcinoma].

To observe the relationship between expression of hypoxia-inducible factor (HIF)-1alpha and chemotherapy response and clinical outcome. Platixal in combination with cisplatin was used in 48 patients with ESCC at advanced stage. platixal 175 mg/m(2), d1; cisplatin 80 mg/m(2), d 2, d 3, d 4, 21 days was one cycle. Chemotherapy response was evaluated. Specimens mentioned above comes from pathology department, the first affiliated hospital of Zhengzhou university. Immuno-histochemistry was used to examine the expression of HIF-1alpha protein in esophageal squamous cell carcinoma. 20 cases normal tissue of esophago was used as control group. chi(2) test and Kaplan-Merier was used to analysis data. HIF-1alpha immunoreactivity was recognized in both cytoplasm and nuclei. HIF-1alpha protein positive expression rate was 43.75% (21/48) in tumor samples, and was negative expression in normal tissue. Among 21 cases with positive expression of HIF-1alpha, there was none complete response case and 5 cases of partial responses, and the response rate was 23.81%; whereas in 27 cases with negative expression of HIF-1alpha, there were 8 cases of complete response and 11 cases of partial responses, and the response rate was 70.37%. There was significant difference between two groups (P < 0.05). In patients of HIF-1alpha positive expression, the median time to tumor progression was 2.0 months, and the median actuarial survival was 6 months, and survival rate was 13.3% in two years; Whereas in patients of HIF-1alpha negative expression, the median time to tumor progression was 5.0 months, and the median actuarial survival was 11.0 months, and survival rate was 42.2% in two years. There was significant difference between two groups (P < 0.05). HIF-1alpha protein expression by immunohistochemistry may be a useful indicator to prediction the chemotherapy response and clinical outcome for esophageal squamous cell carcinoma.

Wu XA ，Sun Y ，Fan QX ，Wang LX ，Wang RL ... -  《-》