Expressions And Clinical Significance Of Osteopontin And EGFR In Esophageal Squamous Cell Carcinoma

Background and ObjectiveEsophageal carcinoma is one of the most frequent malignant tumors in our country, among which the mortality rate is the fourth. Among the total, morbidity rate and mortality rate is the highest. It acutely jeopardizes the physical health of people in our country, so investigating mechanism of the occurrence and development of esophageal carcinoma has becomed one of the investigative hot spots.Osteopontin (OPN) was firstly reported by Senger in 1979 as a phosphoprotein secreted by malignantly transformed epithelial cells. OPN is secreted glycoprotein which is rich in aspartate and sialic acid residues and contains several functional domains, which contain a specific sequence Arg-Gly-Asp(RGD). Through this sequence it can bind to its microenvironment which is growingly needed and called by extracellular matrix(ECM). OPN can mediate interactions of cell-matrix and cellular signal transduction through binding with integrin and CD44 receptors. Recently, more and more datas have manifested that OPN expressed up-regulatedly in many tumors and was closely relative to angiogenesis of tumor,metastasis and invasion,prevention of apoptosis and so on .With the finding of epidermal growth factor(EGF) in 1962 and the obtaining of completed cDNA epidermal growth factor receptor(EGFR) in 1984 and the penetrating investigation of cell signaling network in nineties, we have realized that as one member of receptor tyrosine kinase superfamily, EGFR and its family members , played important regulating effects on the generation,survivorship and differentiation of endepidermis origined cell through the stimulating of corresponding ligand of EGF et al and self phosphorylation receptor participating in cellular growth signal transmit. In recent years, the research of correlation of EGFR and oncogenes reveales that cell Src(c-Src) oncogene and EGFR have not only high homology but also overexpress in many human tumors. It indicated that EGFR and its family members possessed oncogene potentially, closely linked with cell transformation .Tumour cells mainly obtain growth vigor through autocrine and paracrine secretion TGF-α, EGF and acting in EGFR, It indicated that the signaling system is important in tumorous genesis and advancement.There are few domestic and foreign reports involving how OPN and EGFR and its relationship with the tumorigenesis and tumorours progression of esophageal squamous cell carcinoma. In this study, immunohistochemistry was used to detect the expressions of OPN and EGFR in esophageal squamous cell carcinoma, investigating their clinical significance, and analyzing the interaction of tumorous genesis and advancement.Materials and Methods1. Sixty specimens resected by surgical intervention were obtained from the second hospital of Jiaozuo City from Januar 1992 to August 2000(the same case included esophageal squamous cell carcinoma and tumor-adjacent normal esophageal tissue beyond 5 cm), which were verified as esophageal squamous cell carcinoma by pathobiology with sections stained by HE, and we taked follow-up of 6-18 months . None of the patients was treated by radiotherapy and chemotherapy.2. S-P immunohistochemistry was used to detect the expressions of OPN and EGFR in pathological tissue of 60 cases of esophageal squamous cell carcinoma and tumor-adjacent normal esophageal tissue.3. The data was analyzed by SPSS10.0 statistical package, through x²-test,Spearman correlation analysis and Kaplan-Meier,Log-rank test, whose value of test a is 0.05.Results1. In 60 cases of esophageal squamous cell carcinoma, the OPN expression of 48 cases is positive80.0 %(48/60). There was no positive expression of OPN in tumor adjacent tissue of 60 cases. The result showed that there was a significant difference between expressions of esophageal squamous cell carcinoma and tumor adjacent tissue(P<0.01). As to esophageal squamous cell carcinoma, OPN was mainly located at cytoplasm of tumor cells. Mostly, OPN expressed in the center of cancer nest, as a correspondence, little in the edge.2. In 60 cases of esophageal squamous cell carcinoma ,the EGFR expression of 43 cases is positive 71. 7 %(43/60). In 60 cases of tumor adjacent tissue, the EGFR expression of 11 cases is positive 18.3%(11/60). The result showed that there was a statistically significant difference for EGFR expression between esophageal squamous cell carcinoma and tumor adjacent tissue(P<0.01). As to esophageal squamous cell carcinoma , the positive particle diameter of EGFR was mainly located at cytoplasm and mero-cytoblast of tumor cells, as a correspondence, no positive in the surrounding matrix.3. In 60 cases of esophageal squamous cell carcinoma, the positive rate of OPN expression in well-differentiated group is 65.5%( 19/29), which is lower than in moderately and poorly differentiated group93.5%(29/31), and the difference had statistical significance(P<0.01). The positive rate of OPN expression in the group with lymphatic metastasis is 97.1%(34/35), which was higher than in the group of no lymphatic metastasis56.0%(14/25), and the difference had statistical significance(P<0.01). According to the standard of TNM staging, the positive rate of OPN expression in the group of I and II stage was 67.7%(22/31), which was higher than in the group of III and IV stage93.1%(26/29), and the difference had statistical significance(P<0.05). According to the infiltrate depth of cancer, the positive rate of OPN expression in the group of T₁ and T₂ is 73.5%(25/34), which was lower than in the group of T3 and T4 88.5%(23/26), and the difference had not statistical significance(P>0.05).4. In 60 cases of esophageal squamous cell carcinoma, the positive rate of EGFR expression in well-differentiated group was 57.7%(15/26),which was lower than in moderately and poorly differentiated group82.4% (28/34) , and the difference had statistical significance(P<0.05). The positive rate of EGFR expression in the group with lymphatic metastasis was 83.9%(26/31),which was higher than in the group of no lymphatic metastasis58.6%(17/29), and the difference had statistical significance(P<0.05). According to the standard of TNM staging, the positive rate of EGFR expression in the group of I and II stage was 51.7%(15/29),which was lower than in the group of III and IV stage 90.3% (28/31) , and the difference had statistical significance(P<0.01). According to the infiltrate depth of cancer, the positive rate of EGFR expression in the group of T₁ and T₂ was 48.0%(12/25),which was lower than in the group of T₃ and T₄ 77.1% (27/35) , and the difference had statistical significance (P<0.05).5. 6-18 months follow-up was undertaked to 60 patients of esophageal squamous cell carcinoma, and 3 cases was losed. The survival rate of the group of OPN positive expression was 39.1%(18/46), was lower than the group of OPN negative expression 72.7%(8/11). Survival rates were compared by Kaplan-Meier and Log-rank test, whose consequence revealed that there were statistically significant differences(P<0.05).6. 6-18 months follow-up was undertaked to 60 patients of esophageal squamous cell carcinoma, and 3 cases was losed. the survival rate of the group of EGFR positive expression was 38.1%(16/42), was lower than the group of EGFR negative expression 66.7%(10/15). Survival rates were compared by Kaplan-Meier and Log-rank test, whose consequence revealed that there was statistically significant difference(P<0.05)7. The correlation analysis to the expression of OPN and EGFR in 60 cases of esophageal squamous cell carcinoma showed that the group of positive coexpression was 38 cases, the group of negative coexpression was 7 cases, and the group of OPN positive expression and EGFR negetive expression was 10 cases, the group of OPN negetive expression and EGFR positive expression was 5 cases. There were positive correlation between them, and their Spearman coefficient correlation was r_s=0.333(P<0.05).Conclusion1. The distribution of OPN was rich in carcinoma cell nests diffusely, and it's expression was closely correlative to differentiated degree,clinical stage and lymphatic metastasis,prognosis. It indicated that OPN mingt be closely correlative to tumorigenesis and tumorours progression.2. EGFR was excessively expressed in esophageal squamous cell carcinoma, and it's expression was closely correlative to differentiated degree,clinical stage,lymphatic metastasis and infiltrative depth,prognosis. It indicated that the excessive expression of EGFR was closely correlative to tumorigenesis and infiltration,metastasis of cancer. 3. The relativity of the expression of OPN and EGFR protein was analysized by statistics. Results showed relative and they might play synergistic effect during the process of tumorigenesis and tumorours progression of esophageal squamous cell carcinoma.