No abstract

Introduction. New therapeutic agents and biomarkers are needed for the treatment of aggressive endometrial cancer subtypes. Recently, HER2 has been recommended to be tested routinely in serous endometrial cancers. The aim of this study is to investigate the correlation between HER2 (ERBB2) protein overexpression and HER2 gene amplification and the relationship of HER2 gene amplification with prognosis in cancers with serous morphology. In addition, the concordance of HER2 testing in paired curettage and hysterectomy specimens is also investigated. Methods. Twenty five serous carcinomas and 8 carcinosarcomas with a serous morphology were included in the study. HER2 staining was performed on whole tissue sections by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). The system, which was proposed by Fader et al was used to evaluate the stainings. Results. Protein overexpression was detected in 27.3% (n = 9) of the cases, and gene amplification in 30.3% (n = 10). A significant positive correlation was found between the two methods ( P < .0001). HER2 IHC revealed a heterogeneous staining pattern, such as intense complete membranous in solid areas, and basolateral in papillary and glandular areas. HER2 gene amplification was significantly associated with shorter overall ( P = .005) and disease-free ( P = .014) survival. The concordence of the results in curettage and hysterectomy specimens was also significantly high. Conclusion. HER2 is an important prognostic and predictive marker for endometrial cancers with serous morphology. HER2 IHC/ISH testing can be performed by using diagnostic curettage specimens which contain enough viable tumor cells. However, pathologists should be aware of the intratumoral heterogeneity for HER2 staining.

Methotrexate (MTX) is an antineoplastic and anti-inflammatory agent which is used in severe diseases. Its use should be limited due to side effects such as nephrotoxicity, myelotoxicity and hepatotoxicity. Nebivolol (NBV), which is a beta blocker and used in the treatment of hypertension, also contributes to vasodilation in tissues by activating endothelial nitric oxide synthase (eNOS) enzyme. The purpose of this study is to research the effect of NBV on MTX-induced nephrotoxicity through the AKT1/Hif-1⍺/eNOS signaling pathway. The rats were randomly divided into three groups of eight each. Groups were control, MTX and MTX+NBV. A single dose of 20 mg/kg MTX was given intraperitoneally to the rats on the first day of the study and 10 mg/kg NBV was given orally to the treatment group for seven days. At the end of the study, rats' blood and kidney tissues were taken for histopathological, immunohistochemical and biochemical examinations. MTX administration was significantly decreased the expression levels of AKT1, eNOS and Hif1α compared to control group (p<0.001 for all), and NBV treatment increased these values compared to MTX group (p<0.001 for all). In conclusion, NBV treatment ameliorated the MTX induced nephrotoxicity via AKT1/Hif-1⍺/eNOS signaling pathway.