Correlation Study Of Osteopotin Expression With Clinicopathological Features And Prognosis In Esophageal Squamous Cell Carcinoma

BackgroundOsteopontin(OPN) which was also called bonesialoprotein I, early T lymphocyteactivation1and secrected phosphoprotein1, is a secreted extracellular matrix(ECM)protein.It can be secreted by many cells, such as osteoclasts, endothelial cells,epithelial cells and activated immune cells (macrophages and T cells) and so on.There is suggested that OPN can participate in a series of physiological andpathological processes, including bone formation, tissue remodeling, inflammation,cell adhesion, migration, invasion and proliferation. Recently studies showed thatOPN interacts with tumor cells and the extracellular matrix, and play an importantrole in malignant tumor development.ObjectiveOsteopontin (OPN) is considered to influence tumorigenesis and/or metastasis inmany tumors. However, its role as validated clinical biomarkers in esophagealsquamous cell carcinoma (ESCC) remain elusive. The purpose of this study is todetect the OPN expression in pathological specimens of primary esophagealsquamous cell carcinoma and metastatic lymph nodes, and to explore the relationshipbetween OPN and clinicopathologic factors, follow-up the short-term effect andevaluate the prognostic significance of OPN in esophageal squamous cell carcinoma. MethodsThe postoperative pathological specimens of newly diagnosed patients wascollected, who was underwent radical resection for esophageal carcinoma. the serumtumor markers CEA, Cyfra21-1and CA19-9before surgery had been detected for allpatients.68cases met the criteria. The expression of OPN in primary tumors andmetastatic lymph nodes was detected with immunohistochemistry staining.Cytoplasmic staining with yellow or brown were positive. The immunohistochemistry(IHC) expression of OPN was categorized as the following grades according to thepercentage of positive tumor cells for each antibody: negative (-);＜10%positivestaining (-);10–50%positive staining (2+);＞50%positive staining (3+).Semiquantitative evaluation and grading of the immunohistochemical staining wasperformed by two investigators independently. Spearman correlation analysis andother statistical methods were used to analyzed the correlation among OPN and Nstage, G stage, AJCC stage, tumor size, depth of invasion, clinical pathological factorsand so on. Progress-free survival (PFS) and overall survival (OS) were determinedafter follow-up and the relationship between OPN and prognosis of the patients wasinvestigated.Results(1) OPN was found in83.8%(57/68) of the patients.OPN were associated withhistology, N stage, G stage, AJCC stage （P=0.017,r=0.290;P=0.002,r=0.362;P=0.028,r=0.266), but not with depth of invasion, tumor volume, location, etc. In68patients,29patients had lymph node metastasis, the positive expression rate of OPNwas48.3%(14/29), which was positively correlated with the N stage (P=0.036,r=0.391).(2) Positive correlations were found between lesion length in X-ray with T stage,N stage (P<0.001, r=0.599; P=0.023, r=0.276) in addition to AJCC stage (P<0.001,r=0.473). No positive correlation was found when the analysis was repeated fordifferentiation, location and tumor volume.(3) The statistically significant relationship between Cyfra21-1and differentiation was found (P=0.041, r=-0.249), but CEA and CA19-9were notassociated with these clinicopathological factors. There were no significantdifferences between the PFS, OS and these tumor markers.(4) PFS was significantly lower in patients with strong osteopontin expressionthan in those with weak osteopontin expression. PFS was significantly lower inpatients with a high lesion length level in X-ray. Their combination (OPN expressionand tumor length in X-ray) was found to be an independent prognostic factor. As forOS, the T stage, N stage, AJCC stage and adjuvant therapy reached statisticalsignificance in the univariate analysis，but no correlation was observed in themultivariate analysis as independent prognostic factor.ConclusionsPositive correlations were observed between OPN and N stage in addition to Gstage. The Progression-free survival (PFS) of the patienst with high OPN levels wasworse than that of those with low OPN levels. Lesion length in X-ray barium imagingis well-correlated with T stage, N stage and AJCC stage.. Combined evaluation ofOPN plus lesion length in X-ray was useful as an independent prognostic indicator forPFS. Further study is warranted to define the correlation of OPN expression withbiological behaviors and prognosis in ESCC.