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Relative Abundanceof EGFR Expression Predictsbenefit From Cetuximab Treatment For Advanced Colorectal Cancer

Posted on:2015-11-22Degree:MasterType:Thesis
Country:ChinaCandidate:W W SunFull Text:PDF
GTID:2284330431478636Subject:Oncology
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Objective and backgroundColorectal cancer (CRC) is one of the most common cancer, with the improvement ofpeople’s living standard, the incidence of colorectal cancer showed a rising trend year by year,it has become one of the leading causes of death worldwide malignant tumor. Research showsthat, the epidermal growth factor receptor (EGFR) mediated signal pathway is one of the mainrisk factors in the process of colorectal cancer. EGFR is a transmembrane tyrosine kinasereceptor, expressed in a variety of solid tumors. Cetuximab (C225) is a monoclonal antibody,in targeted drug in the typical position, excellent antitumor activity, significantly enhance theefficacy of chemotherapy. Research shows that some factors have predicted the cetuximabefficacy, but the current prediction index of cetuximab’s efficacy is still not get confirms inresearch except KRAS gene, new studies are urgently needed to promote CRC targetedtherapy.Immunohistochemistry method was used to detect the abundance of EGFR expression inCRC tumor tissue samples and analyze its relationship with the clinical factors and prognosisof colorectal cancer, which provide the basis for personalized treatment of advanced CRC.MethodsCollection paraffin embedded tumor samples from67cases of patients treated withcetuximab in Shandong Tumor hospital,recording the clinical characteristics and treatment of patients. The response to treatment was evaluated according to the RECIST1.0criteria,response rate(RR), progression-free survival(PFS) and overall survival(OS) were analyzedretrospectively. Immunohistochemistry was used to detect the expression of EGFR in CRCtumor tissue samples.Immunohistochemical scoring:0points for the expression of EGFR wasnegative (-),1~4can be divided into weak positive (+),5~8is moderate positive (++),9~12is strong positive (+++). Low expression (+,-) high expression (++~+++).Statistical analysisusing SPSS17.0software, the analysis of EGFR protein expression and gender, age, KPSscore, location of tumor, differentiation and stage of the cancer by chi square test; survivalanalysis using the Kaplan-Meier method, the related factors of prognosis model using COXon curative effect analysis;the difference has statistics significance (P<0.05).Results1.The positive expression of EGFR in patients with tumor tissues was67%(45/67), thenegative is22cases,18cases is weak positive,15cases is moderate positive,12cases isstrong positive. The high expression of EGFR in male patients is21cases, the positive ratewas50%; high expression in female patients is6cases, the expression rate is24%; twogroups of expression differences were statistically significant (P <0.05). But the expression ofEGFR in age, KPS score, location of tumor, differentiation stage, there was no significantdifference (P>0.05).2. None of the CR patients in the study,13cases was PR, the response rate(CR+PR)was19.4%,12cases is SD (17.9%), the disease control rate (CR+PR+SD) was37.3%,42cases was PD (62.7%). The low expression of EGFR group was10%, the high expression ofEGFR group was33.3%, there was significant difference between two groups (P<0.05). Lowexpression of EGFR group of disease control rate was35%, the high expression of EGFRgroup of disease control rate was40.7%, there was no significant difference between twogroups (P>0.05).3. EGFR low expression group and high expression group, The median OS was11and12months in EGFR low and high expression group respectively, the one year survival rateswere47.4%and48.1%; two year survival rates were25.8%and28.9%, there was nosignificant difference (P=0.781), the median PFS was5and6months; there was no significant difference (P=0.259). The effects variables of OS in COX regression modelanalysis showed that: only clinical stage (P=0.026) was statistically significant differences.Conclusions1.The EGFR expression of colorectal cancer was associated with gender, but notassociated with age,KPS score, location of tumor, differentiation and stage of the cancercancer related EGFR, and patient age, KPS score, location of tumor, differentiation and stageof the cancer.2.The response rate of high EGFR expression group was significantly higher than that oflow expression group, it suggested that EGFR expression and short-term efficacy ofcetuximab has certain correlation.3.The abundance of EGFR expression and PFS, OS are not relevant, clinical stage is themain factors that influencing the prognosis of OS.
Keywords/Search Tags:Colorectal cancer, epidermal growth factor receptor, expression abundance, cetuximab
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