Relationship between COX-2 and cell cycle-regulatory proteins in patients with esophageal squamous cell carcinoma.

AIM: To investigate the correlation between cyclooxygenase-2 (COX-2) and cell cycle-regulatory proteins in patients with esophageal squamous cell carcinoma (ESCC). METHODS: One hundred and two surgically obtained specimens of ESCC were randomly collected. All specimens were obtained from patients who had not received chemo- or radiotherapy prior to surgical resection. Twenty-eight specimens of normal squamous epithelium served as controls. The expression of COX-2, Ki-67, cyclin A and p27 was examined by immunohistochemistry. The Pearson test was used to analyze the relationship between groups. RESULTS: The protein level of COX-2, Ki-67 and cyclin A was significantly higher in ESCC than in normal squamous epithelium (74.7 ± 61.2 vs 30.2 ± 43.4, 64.0 ± 51.6 vs 11.6 ± 2.3, 44.2 ± 32.2 vs 11.7 ± 5.0, respectively, all P < 0.01). In contrast, the protein level of p27 was significantly lower in ESCC than in normal squamous epithelium (182.0 ± 69.0 vs 266.4 ± 28.0, P < 0.01). In ESCC, COX-2 expression was correlated with T stage, the score of T1-T2 stage was lower than that of T3-T4 stage (55.0 ± 42.3 vs 83.0 ± 66.5, P < 0.05), and Ki-67, cyclin A and p27 expressions were correlated with the tumor differentiation (43.8 ± 31.7 vs 98.4 ± 84.8, 32.0 ± 19.0 vs 54.1 ± 53.7, 206.2 ± 61.5 vs 123.5 ± 68.3, respectively, all P < 0.01). COX-2 expression was positively correlated to Ki-67, cyclin A and negatively correlated to p27 expression in ESCC (r = 0.270, 0.233 and -0.311, respectively, all P < 0.05). CONCLUSION: The expression of COX-2 is correlated with tumor cell invasion and is closely related to the cell proliferation in patients with ESCC.

Expression of thymidylate synthase and glutathione-s-transferase pi in patients with esophageal squamous cell carcinoma.

AIM: To investigate the expression of thymidylate synthase (TS) and glutathione-s-transferase pi (GST-pi) in esophageal squamous cell carcinoma and their association with the clinicopathologic characteristics. METHODS: Immunohistochemical methods were used to detect the expression of TS and GST-pi in surgically resected formalin-fixed, paraffin-embedded esophageal squamous cell carcinoma (ESCC) tissue sections from 102 patients (median age, 58 years) and in 28 normal esophageal mucosa (NEM) samples. The relationship between TS and GST-pi expression and clinicopathologic factors was examined. RESULTS: The expression of TS and GST-pi was not statistically significantly associated with age of the patients, tumor size, lymph node metastasis, depth of invasion or tumor stage. TS staining was positive in 17.86% of normal esophageal mucosa and in 42.16% of ESCC samples (P < 0.05). The expression level of TS was not only significantly lower in well-differentiated (21.88%) than in poorly-differentiated carcinomas (51.43%, P < 0.05), but was also significantly higher in samples from male patients (46.51%) than from female patients (18.75%, P < 0.05). GST-pi was positively stained in 78.57% of normal esophageal mucosa and in 53.92% of ESCC samples (P < 0.05). The expression level of GST-pi was also significantly higher in well-differentiated carcinomas (65.63%) than in poorly-differentiated carcinomas (35.00%, P < 0.05). CONCLUSION: The expression of TS and of GST-pi may be used as molecular markers for the characterization of ESCC. Poorly-differentiated cells showed increased expression of TS and reduced expression of GST-pi.

Relationship between proliferative activity of cancer cells and clinicopathological factors in patients with esophageal squamous cell carcinoma.

AIM: To assess whether the molecular markers of malignant tumors could improve the understanding of tumor characteristics, and to observe the characteristics of expression of cell cycle markers Ki-67 and cyclin A in esophageal carcinoma and to analyze the relationship between proliferative activity of cancer cells and clinicopathological factors. METHODS: Seventy of surgically resected esophageal squamous cell carcinoma (SCC) were examined by immunohistochemistry utilizing commercially available antibodies. Nuclear staining was regarded as a positive result. At least 50 fields in each tumor and non-tumor section were evaluated at a medium power (X200) to determine the proportion of tumor cells and the staining intensity of nuclei in the entire sections. RESULTS: Ki-67 and cyclin A were only expressed in base cells of normal esophageal mucosa. The positive immuno-staining of nuclei of SCC was significantly higher than that in normal esophageal mucosa (t=13.32 and t=7.52, respectively, P<0.01). The distribution of positively stained was more diffuse and stronger in poorly differentiated SCC. Both Ki-67 and cyclin A expressions were related to histological grades of tumors (t=3.5675 and t=3.916; t=2.13, respectively, P<0.05) but not to the sex and age of the patients, tumor size, lymphatic invasion, location, or stage grouping. CONCLUSION: The proliferative activity of cancer cells may be understood by immunohistochemistry of Ki-67 and cyclin A in Chinese patients with esophageal SCC. These cell cycle markers may serve as an indicator of cancer cell proliferation rate. The overexpression of cell cycle markers Ki-67 and cyclin A suggests the poor SCC differentiation in patients with esophageal carcinoma.