AUTOPHAGY BIOMARKERS SQSTM1/P62 AND BECLIN-1 EXPRESSION IN BREAST CARCINOMA AND THEIR CLINICOPATHOLOGICAL SIGNIFICANCE

Background: Clarifying the different mechanisms of molecular carcinogenesis of breast carcinoma could enable its better management, improving its prognosis and decreasing patient?s mortality. Autophagy is the process of lysosomal degradation which could remove the damaged components so as to preserve cells homeostasis. Autophagy had a complicated role in cancer as it might inhibit or stimulate cancer progression which depend on the type of cancer. Several proteins which control autophagy had been discovered in human cells such as Beclin-1and SQSTM1/p62 (Sequestosome-1) that played important roles in autophagy. Aim of the work: This study aimed to assess expressions of autophagy markers SQSTM1/p62 and Beclin-1 in breast carcinoma comparing expression of both markers with clinicopathological parameters of that type of cancer. Patients and methods: SQSTM1/p62, Beclin-1 expression was evaluated using immunohistochemistry on sixty paraffin blocks of breast carcinoma. Then correlations between their expression levels and clinicopathological parameters were done. Results: SQSTM1-p62 overexpression in breast carcinoma was strongly related to higher grade (=0.002) and American Joint Committee on Cancer staging system (AJCC stage) of the tumor, aggressive molecular type (=0.009), presence of lymph node metastases (=0.041), high KI67 index (p<0.001), negative ER& PR hormonal receptors (=0.01), Her2 neu expression (=0.03), presence of distant metastasis (p=0.011). The sensitivity of p62 over-expression as a predictor for advanced stage of breast carcinoma was 72.4 and the specificity was 97.9. Beclin-1 low expression was significantly correlated with aggressive molecular type (=0.004), higher grade (p<0.001) and AJCC stage of the tumor (p=0.002), presence of lymph node metastases (=0.041), high KI67 index (p<0.001), negative ER& PR hormonal receptors (=0.003), high Her2 neu expression (=0.006), presence of distant metastasis (p=0.011). But it had no significant correlation with histopathological subtype of breast cancer. The sensitivity of low Beclin-1 expression as a predictor For advanced stage of breast carcinoma was 85.5 and the specificity was 97.9. We found an inverse relationship between p62 and Beclin-1 (Spearman?s r= ? 0.806), Conclusion: SQSTM1-p62 over expression is a marker of poor prognosis, but Beclin-1 overexpression was a marker of good prognosis in breast carcinoma.