To investigate the significance of epidermal growth factor receptor (EGFR) in thyroid carcinoma, the expression of EGFR in 81 samples of thyroid carcinoma were determined by immunohistochemical SP method and comparison among thyroid carcinoma, thyroid adenomas and normal thyroid tissue adjacent to the cancer were made. The results showed: EGFR expression was positive in 45 cases (55.6%) of thyroid carcinoma with no positive expression either in thyroid adenomas or normal thyroid tissue adjacent to the cancer (Ｐ＜0.01). There were no statistical differences between EGFR positive rate and thyroid carcinomatous pathological type, clinical stage, depth of invasion, lymph node metastasis or patients′ postoperative survival time (Ｐ＞0.05). This data suggests that expression of EGFR in thyroid carcinoma is associated with its autonomous growth and malignant phenotype, but it is probably not a useful index for assessing the biological behavious and prognosis of thyroid carcinoma.
Objective To observe the effect of gefitinib on expression of epidermal growth factor receptor (EGFR) in bile duct epithelial cells, and the feasibility of inhibiting hyperplasia of bile duct epithelial cells with gefitinib. Methods Sixty-one patients with hepatolithiasis having to be in hospital for surgery from the First People’s Hospital of Shuangliu county were selected, with 25-65 years old, average 46.92 years. The patients were randomly divided into therapy group and control group. There were 30 cases in therapy group, in which fine duct was placed on lesion bile duct during operation, and through whom gefitinib solution was perfused after operation. There were 31 cases in control group with only T tube drainage after operation. The bile duct sample was obtained respectively during the operation and 6 weeks and 12 weeks after operation. The histology and expression change of EGFR were observed by HE staining, immunohistochemistry and RT-PCR method respectively. Results There were no significant differences in pathohistology changes of bile duct and the EGFR protein and mRNA expression between therapy group and control group during operation. The hyperplasia of epithelium mucosae and submucosal gland in the therapy group were obviously decreased as compared with those in control group, the EGFR mRNA and protein expression in therapy group were weaker than those of control group （Plt;0.05） 6 weeks and 12 weeks after gefitinib treatment. Conclusion EGFR is overexpressed in the chronic proliferative cholangitis, and continuously local application of gefitinib after operation can specifically interrupt the activation and expression of EFGR and then effectively inhibit the hyperplasia of bile duct epithelial cells.
Abstract： Objective To investigate the expression and correlation of phosphatase and tensin homologue deleted on chromosome ten(PTEN)， epidermal growth factor receptor(EGFR) and Ki-67 in human thymic tumors, and their possible role in tumor genesis， infiltration and metastasis. Methods The expression of PTEN， EGFR and Ki-67 were detected by using SP immunohistochemical technique in 45 cases of thymic tumors and 5 cases of normal thymic tissues. Results In 5 cases of normal thymic tissues, the expression of PTEN was bly positive, whereas EGFR and Ki -67 were weakly positive or negative. In 45 cases of thymic tumors, the positive ratio of PTEN were significantly reduced from benign thymoma， invasive thymoma to thymic carcinoma (χ2=7.808, P=0.020), but the positive ratio of EGFR and Ki-67 were gradually increased(χ2=8.032, 0.018，7.006；P=0.030). The positive ratio of PTEN， EGFR and Ki-67 protein were significantly related to Levine classification, Masaoka staging and lymph node metastasis (Plt;0.05). PTEN positive cases were negatively correlated with EGFR and Ki-67(r=－0.632，－0.653；Plt;0.01), EGFR positive cases were positively correlated with Ki-67 in thymic tumors(r=0.807,Plt;0.01). Conclusions Reduced or absent PTEN and increased EGFR and Ki-67 expression might play an important role in the genesis， invasiveness and metastasis of thymic tumors. The expression of PTEN is bly associated with the expression of abnormal EGFR and Ki-67. Detection of the three protein expressions simultaneously might be more helpful in making an early diagnosis of the tumors jndgement of theirs malignant degree，invasiveness and metastasis capacity, as well as the prognosis.
ObjectiveTo investigate the value of serum soluble CD146 (sCD146) in determining acquired epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance in lung adenocarcinoma.MethodsA total of 144 lung adenocarcinoma EGFR sensitive patients in People’s Hospital of Zhengzhou University diagnosed from January 2016 to December 2016 were recruited in the study. According to the different time of taking drugs, the patients were divided into a non-medication group (31 cases), a 1 to 3 month treatment group (25 cases), a 4 to 6 month treatment group (19 cases), a 7 to 12 month treatment group (25 cases), a drug-resistant group (24 cases), and a nonresistant group up to 1 year of treatment (20 cases). The serum levels of sCD146, carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) were measured by ELISA and chemiluminescence and compared between different period of medication. The relationship of serum sCD146 with tumor markers (CEA, NSE) and tumor related clinical parameters (age, gender, tumor stage, metastasis, tumor diameter, number of the lesions) were analyzed.ResultsThe serum sCD146 level was minimum in the non-medication group that did not receive pioglitazone treatment, highest in the 1 to 3 month treatment group (early treatment period), and declined with duration of medication until resistance occurred without significant difference (P>0.05). The level of sCD146 of the drug-resistant group was significantly lower than that of all nonresistant groups, with significant difference (allP<0.05), but still higher than that of the non-medication group (P<0.05). The serum sCD146 levels in the nonresistant patients with medication over 1 year and within 1 year were similar (P>0.05), and significantly higher than the non-medication group and drug-resistance group (allP<0.05). The serum CEA levels did not differ significantly between 6 groups (P>0.05). The serum NSE level of the 4 to 6 month treatment group was lower than that of the 7 to 12 month treatment group (P<0.05), but both in the normal reference range. The NSE levels did not differ in any other groups (P>0.05). Serum sCD146 was associated with metastasis (P<0.05), but not associated with serum CEA or NSE, nor with sex, age, tumor staging, tumor diameter or lesion number (allP>0.05).ConclusionsCD146 may be involved in the mechanism of TKI killing tumor cells and the mechanism of TKI resistance, and may be a serological marker for monitoring the efficacy of TKI and judging the resistance of TKI.
Objective To investigate the roles of NF-κB and EGFR in hepatolithiasis associated with intrahepatic cholangiocarcinoma. Methods Ninety cases of liver tissue specimens from hepatectomies performed in the 2nd Affiliated Hospital of Sun Yat-sen University between August 1989 and June 2009 were enrolled in the study. Among them, 33 cases of hepatolithiasis associated with intrahepatic cholangiocarcinoma were considered as observing group, 32 cases of hepatolithiasis as control group, and 25 cases of normal bile duct tissues as normal control group. The SP method of immunohistochemical staining was applied to detect the expressions of NF-κB and EGFR in intrahepatic biliary ducts epithelial cells, and their relations with clinicopathologic factors and the accumulated survival rate of hepatolithiasis associated with intrahepatic cholangiocarcinoma were analyzed. Results Expression rates of NF-κB and EGFR were gradually raised from normal control group, control group to observing group (Plt;0.01). Expression of EGFR in tumor patients was related to histopathologic differentiation grading and the depth of tumor invasion (Plt;0.05), but not to gender, age, or lymph node metastasis (Pgt;0.05)； there were no significant relationships between the expression of NF-κB and factors described above (Pgt;0.05). The survival rate of patients with tumor expressed EGFR was significantly lower than that of patients with tumor non-expressed EGFR (Plt;0.01). Conclusions NF-κB expression is in the early stage during intrahepatic cholangiocarcinoma genesis. NF-κB and EGFR play cooperating roles during hepatolithiasis carcinogenesis process. Over expression of EGFR is related with poor differentiation and prognosis of tumor.
Objective To evaluate the clinical significance of epidermal growth factor receptor EGFR) mutations in the treatment of non-small cell lung cancer ( NSCLC) . Methods Plasma DNAs solated fromblood specimens of 170 NSCLC patients, who were admitted in the First Affiliated Hospital of uangzhou Medical College from December 2005 to December 2007, were subjected to the test of EGFR utant-enriched PCR. The correlation of mutant detection with clinical characteristics was analyzed as well.Results Out of the total 170 patients, EGFR mutations were identified in 77 cases ( 77 /170, 45. 3% ) .EGFR mutations were more frequent in the patients with adenocarcinoma ( P lt; 0. 001) and in the nonsmokers P =0. 001) . In the 33 patients treated with gefitinib, those with mutations ( + ) showed a higher esponse rate and prolonged progression-free survival after the treatment compared with those with mutations( - ) ( P =0. 001 and 0. 001, respectively) . Conclusions EGFR active mutations can be specifically and ensitively detected by EGFR mutant enriched PCR assay. Plasma EGFR mutants detection is valuable in uiding clinical decision.
The tyrosine kinase activity of epidermal growth factor receptor (EGFR) plays a key role in tumor cell proliferation, invasion, migration, and drug resistance. Studies have shown that non-small cell lung cancer patients with somatic driver gene EGFR mutations are sensitive to and can benefit from EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Nevertheless, EGFR-TKIs-related adverse events should not be ignored. Common adverse events such as diarrhea, acne-like rash and paronychia are usually manageable; although the incidence of interstitial lung disease is low, once it occurs, it is a serious threat to patients' life, and its pathogenesis is still unclear. There is very limited animal experimental and clinical research evidence on the potential mechanism of EGFR-TKIs-related interstitial lung disease in the available literature. Based on this, this article reviews the association between EGFR-TKIs and interstitial lung disease, at the same time, also discusses the research progress of EGFR-TKIs-related interstitial lung disease in combination with cytotoxic drugs or immunotherapeutic drugs and EGFR-TKIs, in order to provide a reference for the prevention and treatment of EGFR-TKIs-related interstitial lung disease in clinical practice in the future.
ObjectiveTo detect expressions of epidermal growth factor receptor (EGFR), BRAF, and K-Ras genes in colorectal carcinoma tissues and explore pathogenesis in colorectal carcinoma. MethodThe expressions of EGFR, BRAF, and K-Ras genes were detected in these 136 colorectal carcinoma tissues and their corresponding adjacent normal colorectal tissues by immunohistochemistry. ResultsThe expressions of EGFR and BRAF in the colorectal carcinoma tissues were significantly higher than those in their corresponding adjacent normal colorectal tissues (P<0.05), but the expression of K-Ras had no significant difference between these two tissues (P>0.05). The expression of EGFR gene was related to the TNM stage, lymphatic metastasis, or degree of differentiation. The expression of BRAF gene was related to the TNM stage. The expression of K-Ras gene wasn,t related to the TNM stage, lymphatic metastasis, or degree of differentiation. The correlation analysis results showed that there was no relation among the EGFR, K-Ras, or BRAF expression. ConclusionsUp-regulated of EGFR and BRAF gene expressions might be related to development of colorectal carcinoma, and role of K-Ras is unclear. Anti EGFR and BRAF target therapy might be benefited for patients with colorectal carcinoma.
ObjectiveTo explore the correlation between expression of thyroid transcription factor-1 (TTF-1) and gene mutation of epidermal growth factor receptor (EGFR) in patients with resectable lung adenocarcinoma (LAC). Method Sixty-seven LAC patients who underwent surgical resection in the Department of Cardiothoracic Surgery of Shanghai No.6 Hospital and Department of Thoracic Surgery, Renji Hospital, School of Medicine of Shanghai Jiaotong University from June 2009 to December 2012 were enrolled in this study. There were 40 male and 27 female patients with their age of 37-79 (56.7±1.8) years. TTF-1 expression was detected by immunohistochemistry. EGFR gene mutation was examined with mutant-enriched polymerase chain reaction. The correlation between TTF-1 expression and EGFR gene mutation was analyzed with corrected chi-square test. ResultsAmong the 67 LAC samples, 57 samples were TTF-1 positive and 10 samples were TTF-1 negative. There was EGFR gene mutation in 44 samples. EGFR gene mutation rate was 73.7% (42/57) in TTF-1 positive patients and 20.0% (2/10) in TTF-1 negative patients. The sensitivity of TTF-1 expression to predict EGFR mutation was 95.5%, and the specificity was 34.8%. ConclusionEGFR gene mutation rate is higher in LAC patients with positive TTF-1 expression. Positive TTF-1 expression can be used to predict EGFR gene mutation in LAC patients.
The incidence and mortality of esophageal cancer in China rank the fifth and fourth, respectively, with squamous carcinoma accounting for more than 90%. Currently, the treatment of esophageal squamous carcinoma mainly includes surgery, chemotherapy, radiotherapy, and endoscopic treatment. However, the 5-year survival rate is only about 20%. At present, the treatment of esophageal squamous carcinoma seems to reach a plateau. Thus, it is urgent to develop new and more effective drugs and treatments. In this paper, the clinical research progresses of epidermal growth factor receptor (EGFR)- targeted therapy of esophageal squamous carcinomas were summarized, including anti-EGFR monoclonal antibodies, such as cetuximab and nimotuzumab, and EGFR-tyrosine kinase inhibitor, such as gefitinib, erlotinib, and ecclinib.