Expression and characterization analysis of EGFR, PI3K and its phosphorylated protein in different subtypes of breast cancer

Abstract

Objective To study the differential expression of epidermal growth factor receptor(EGFR),phosphoinositide 3 kinase(PI3K) and its phosphorylated protein p-PI3K,and to analyze the correlation between the expression of the three proteins and clinicopathological features in different subtypes of breast cancer,and to investigate the role of PI3K and its phosphorylated protein p-PI3K in the PI3K/Akt/mTOR signaling pathway in the development and progression of breast cancer.Methods 117 cases of newly diagnosed invasive breast cancer were selected from Jan.2005 to Jun.2010 in Affiliated Cancer Hospital of Xinjiang Medical University,and molecular typing was made by immunohistochemistry results of ER,PR and HER-2,including triple negative breast cancer group(TN group,28 cases),HER-2 over-expression breast cancer group(HER-2 + group,12 cases)and luminal epithelial breast cancer group (Luminal group,77 cases).Immunohistochemistry was used to detect the expressions of PI3 K,p-PI3 K and EGFR in breast carcinoma and its adjacent tissues,and to analyze their expression characteristics in breast cancer and its different subtypes,as well as the correlations between their expressions and clinicopathological features.Results (1) Expressions of PI3K,p-PI3K and EGFR in breast cancer tissues and the adjacent tissues were different:the positive expression rates of PI3K and p-PI3K in breast cancer tissues were higher those that in the adjacent tissues,and the difference had statistical significance (x2 =27.589,P ＜ 0.001 ;x2 =49.327,P ＜ 0.001).EGFR expressions were significantly different in breast cancer tissues and the adjacent tissues(x2 =10.920,P =0.004).(2) Expression of PI3K,p-PI3K and EGFR in different subtypes of breast cancer was different:the positive expression rates of PI3k and p-PI3K were similar between TN group and HER-2 + group,but lower than those in Luminal group,while the expression of EGFR in TN group was significantly higher than those in the other two groups.Expressions of PI3K,p-PI3K and EGFR were statistically different in different subtypes of breast cancer (x2 =9.842,P =0.037 ;x2 =13.423,P =0.006 ;x2 =12.410,P =0.012).Likewise,expressions of PI3K,p-PI3K and EGFR were different between the three different groups (x2 =7.835,P =0.020;x2 =11.791,P =0.003).Expressions of PI3K and EGFR were statistically different only in TN group and Luminal group.There were statistically difference in p-PI3K expression between TN group and Luminal group,and between HER-2 + group and Luminal group(x2 =9.336,P =0.009 ;x2 =7.361,P =0.025).There was no significant difference in the other groups.(3)The correlations of the expressions of PI3 K and p-PI3 K in breast cancer and three different subtypes:compared with PI3K,the positive expression rate of p-PI3K significantly increased in breast cancer,and showed significant positive correlation(r =0.324,P ＜ 0.001).However,this correlation was different between the three different groups.Expressions of PI3k and p-PI3K showed a positive correlation in Luminal group (r =0.385,P =0.001),and there was no relation in TN group and HER-2 group (r =0.222,P =0.257 ; r =0.410,P =0.185).Further stratified analysis showed that the expression status of EGFR affected the expressions of PI3K and p-PI3K in breast cancer.No significant correlation was found in the EGFR negative group(r =0.186,P =0.227),while there was significant positive correlation in EGFR positive group(r =0.396,P =0.001).(4)Relations between expressions of PI3K and p-PI3K and clinicopathological features of breast cancer:there were differences in expressions of PI3K between different ethnic Han and Uighur,as well as between different histological grades (x2 =7.846,P =0.020 ;x2 =7.160,P =0.028),and no correlation with tumor size,axillary lymph node status and tumor staging was found.The expression of p-PI3 K was not related to the clinicopathological features in breast cancer.Conclusions EGFR may play a role in carcinogenesis of breast cancer through activation of the PI3K,and the expression status of EGFR affects the activation of PI3 K signaling pathway.After stimulated by the upstream impact factors,PI3K can be activated and play an important role in the signal transduction pathway.The expressions of PI3K and its phosphorylated proteins p-PI3K are different in different subtypes of breast cancer.The results suggest that individual treatment should be made according to different types of breast cancer,and PI3K may become a new target for breast cancer treatment. Key words: Breast cancer; Molecular subtypes; PI3K signaling pathway; Phosphorylation; Epidermal growth factor receptor