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Cytokeratin (CK) immunohistochemistry can play an important role in breast carcinoma evaluation. We evaluated the expression of a panel of commonly used CKs in a large cohort of breast cancers and assessed its correlation with other biomarkers and breast cancer subtypes. Expression of CK7, CK8, CK18 and CK19 was observed in more than 90 % of all breast carcinomas in this study, confirming their efficacy in immunohistochemical identification of breast cancer. A combination of CK8 and CK7 gave the highest sensitivity for detection of a minute number of breast cancer cells. Expression of other CKs, including CK5/6, CK14 and CK20, correlated positively with high tumour grade. The expression of CK5/6 and CK14 in a significant number of high-grade tumours raised concern regarding the use of absence of their expression to identify breast carcinoma. For identification of the basal subtype, CK5/6 gave a higher detection rate than CK14. CK20 expression was found more frequently than reported in previous studies, might constitute an indicator of poor prognosis and may be associated with the molecular apocrine subtype. This study highlights the diagnostic and prognostic relevance of the unique CK expression patterns in breast cancer.

AR expression was different in ER+ and ER- cancers and had different clinical implications. AR alone may not be a good marker for MA subtype. Its expression in MA may have substantial prognostic implication and as such warrants further validation.

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The aim of this study was to investigate the effect and possible mechanism of Astragaloside IV (AS-IV) on retarding the progression of diabetic nephropathy (DN) in a type 2 diabetic animal model, db/db mice. Eight-week-old male db/db diabetic mice and their nondiabetic littermate control db/m mice were used in the present study. AS-IV was administered to the db/db mice by adding it to standard feed at a dose of 1g/kg for 12 weeks. Renal injury was assessed by urinary albumin excretion (UAE) and Periodic acid-Schiff staining. The protein expression levels of mitochondrial quality-control-associated proteins were evaluated using Western blotting and immunohistochemical staining analysis. At the end of the experiment, db/db mice showed overt renal injury, as evidenced by increased UAE, increased urinary N-acetyl-β-D-glucosaminidase (NAG), expansion of mesangial matrix, and increased renal tubular area. AS-IV administration significantly reduced UAE and urinary NAG and ameliorated the renal pathologic injury seen in db/db mice. Furthermore, the expression of dynamin-related protein 1 (Drp-1), mitochondrial fission protein 1 (Fis-1), and mitochondrial fission factor (MFF), the main regulators of mitochondrial fission, was significantly increased in db/db mice. Moreover, PTEN-induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy was abnormally activated in db/db mice. AS-IV significantly reduced renal Drp-1, Fis-1, and MFF expression and downregulated PINK1/Parkin-mediated mitophagy in db/db mice. However, mitochondrial biogenesis and mitochondrial fusion-associated protein levels were not significantly different between db/m and db/db mice in our study, with or without AS-IV treatment. In conclusion, administration of AS-IV could retard DN progression in type 2 diabetes mice, which might be associated with restoration of the mitochondrial quality control network.