[Association of hypoxia-inducible factor 1α expression with microlymphatic vessel density and lymph node micrometastasis in rectal cancer].

OBJECTIVE: To explore the association of the expression of hypoxia-inducible factor 1α (HIF-1α) with microlymphatic vessel density(MLVD) and lymph node micro-metastasis in rectal cancer. METHODS: The experimental group consisted of 40 middle-low rectal cancer specimens pathologically confirmed at the First Affiliated Hospital of Anhui Medical University between 2000 and 2003. Forty samples of normal tissues taken from the corresponding area around the cancer were used as the control group. Immunohistochemistry was used to detect HIF-1α expression and MLVD in both the tumor tissues and the adjacent normal tissues. Lymph node micrometastasis was ascertained using immunohistochemical staining with CK20. RESULTS: In rectal cancer tissues, the HIF-1α expression was 77 386±14 911 and MLVD was 7.3±0.7, significantly higher than those in normal adjacent tissues(33 092±5877 and 0.3±0.2, both P<0.01). The HIF-1α expression was positively correlated with MLVD in rectal cancer(r=0.781, P<0.01). Thirty-one patients had no lymph nodes metastasis and 10 had micrometastasis. The HIF-1α expression and MLVD in specimens with lymph node micrometastasis was significantly higher than that in those without lymph node micrometastasis(P<0.05). CONCLUSION: HIF-1α and MLVD play important roles in the development of rectal cancer,which may promote lymphatic micrometastasis in rectal cancer.

Microvessel density is a prognostic marker of human gastric cancer.

AIM: To investigate whether microvessel density (MVD) is related with prognosis in gastric cancer patients, and the expression of cyclooxygenase-2 (COX-2) and vessel endothelial growth factor (VEGF) so as to determine the possible role of COX-2 and VEGF in gastric cancer angiogenesis. METHODS: Forty-seven formalin-fixed paraffin-embedded tissue samples of gastric cancer were evaluated for COX-2, VEGF by immunohitochemical staining. To assess tumor angiogenesis, MVD was determined by immunohitochemical staining of endothelial protein factor VIII-related antigen. The relationship among COX-2 and VEGF expression, MVD, and clinicopathologic parameters was analyzed. RESULTS: Among the 67 samples, high MVD was significantly associated with lymph node metastasis and poor survival. Multivariate survival analysis showed that MVD value and lymph node metastasis were independent prognostic factors. The expression rate of COX-2 and VEGF was significantly higher than that of the adjacent tissues. COX-2 and VEGF expression in gastric cancer was significantly correlated with tumor differentiation and depth of invasion, but not with survival. The mean MVD value of COX-2 or VEGF positive tumors was higher than that of COX-2 or VEGF negative tumors. A significant correlation was found between the expressions of COX-2 and VEGF. CONCLUSION: MVD may be one of the important prognostic factors for gastric cancer patients. COX-2 and VEGF may play an important role in tumor progression by stimulating angiogenesis. VEGF might play a main role in the COX-2 angiogenic pathway. The inhibition of angiogenesis or COX-2, VEGF activity may have an important therapeutic benefit in the control of gastric cancer.

[Expression and significance of cell cycle regulators in gastric carcinoma].

BACKGROUND & OBJECTIVE: Abnormality of cell cycle regulation is an important cause of cell over-proliferation and oncogenesis. But the relationship between cell cycle regulators and gastric carcinoma is uncertain. This study was to investigate the expression and significance of cell cycle regulators, including P16(INK4), Cyclin D1, P21(WAF1), and P53, in gastric carcinoma. METHODS: The expressions of P16(INK4), Cyclin D1, P21(WAF1), and P53 in 53 specimens of gastric carcinoma were observed by SP immunohistochemistry. Multivariate Cox regression was used to analyze factors affecting prognosis. RESULTS: Positive rate of P53 in gastric carcinoma was higher than that in adjacent tissues (60.4% vs. 0, P < 0.01); those in well, and poorly differentiated adenocarcinoma were significantly higher than that in mucoid carcinoma (65.4%, and 68.2% vs. 0, P < 0.01). Over-expression rate of Cyclin D1 in gastric carcinoma was higher than that in adjacent tissues (69.8% vs. 5.7%, P < 0.01). Positive rate of P16(INK4) in gastric carcinoma was lower than that in adjacent tissues (60.3% vs. 88.6%, P < 0.05). Positive rate of P21(WAF1) in gastric carcinoma was lower than that in adjacent tissues (26.4% vs. 56.6%, P < 0.01). Positive rate of P16(INK4) was significantly related with the depth of tumor invasion (P < 0.05), and lymph node metastasis (P < 0.01). Multivariate Cox regression analysis indicated that lymph node metastasis and the expression of P16(INK4) were independent prognostic factors of gastric carcinoma. CONCLUSIONS: Down-regulation of P16(INK4) and P21(WAF1), and over-expression of Cyclin D1 and P53 are significantly related to genesis and progression of gastric carcinoma. Down-regulation of P16(INK4) may be correlated to infiltration, metastasis, and prognosis of gastric carcinoma.

Relationship between the expression of human telomerase reverse transcriptase gene and cell cycle regulators in gastric cancer and its significance.

AIM: To investigate the expression of human telomerase reverse transcriptase gene (hTRT) in gastric cancer (GC) and its relevance with cell cycle regulators including P16INK4, cyclin and P53. METHODS: In situ hybridization (ISH) for hTRT mRNA was performed in 53 cases of gastric cancer and adjacent cancerous tissues. Immunohistochemical staining (S-P method) for hTRT protein, P16INK4, cyclinD1 and P53 was performed in 53 cases of GC and adjacent cancerous tissues. RESULTS: Of 53 cases of GC, the expression of hTRT mRNA and hTRT protein was significantly higher than the expression of hTRT mRNA and hTRT protein in adjacent canerous tissues (P<0.01), the positive rates of hTRTmRNA and hTRT protein were 79.2 % and 88.6 %. There was a stastical difference of the expression of hTRT protein among well differentiated adenocarcinoma, poorly differentiated adenocarcinoma and mucoid carcinoma. And there was a highly significant positive correlation between the expression of hTRT mRNA and hTRT protein (r=0.625, P<0.01). However, the expression of hTRT mRNA and its protein in GC were not related with other clinicopathological parameters including gender, age, location and size of neoplasm, invasion depth, lymph node metastasis and clinical stage. There was a significant positive correlation between the expression of hTRT mRNA and cyclinD1 protein (r=0.350, P<0.01). There was a significant positive correlation between the expression of cyclinD1 protein and hTRT protein (r=0.549, P<0.01), so was between P53 and hTRT protein (r=0.319, P<0.05). CONCLUSION: The expression of hTRT gene is correlated significantly to the specific defects of cell cycle on G1/S check point; telomerase activity may depend on cell cycle in gastric cancer and it is available to clarify the molecular mechanism of telomerase activity regulation. The expression of hTRT mRNA and hTRT protein in GC is significantly different from the expression of hTRT mRNA and hTRT protein in adjacent cancerous tissue which indicates that these targets are correlated closely to the occurrence of GC and can provide important morphologic index for diagnosis of GC.