Epithelial-mesenchymal transition associated markers in sarcomatoid transformation of clear cell renal cell carcinoma.

Epithelial-mesenchymal transition (EMT) plays a pivotal role in the development and progression of many cancers. Partial EMT (pEMT) could represent a critical step in tumor migration and dissemination. Sarcomatoid renal cell carcinoma (sRCC) is an aggressive form of renal cell carcinoma (RCC) composed of a carcinomatous (sRCC-Ca) and sarcomatous (sRCC-Sa) component. The role of (p)EMT in the progression of RCC to sRCC remains unclear. The aim of this study was to investigate the involvement of (p)EMT in RCC and sRCC. Tissue samples from 10 patients with clear cell RCC (ccRCC) and 10 patients with sRCC were selected. The expression of main EMT markers (miR-200 family, miR-205, SNAI1/2, TWIST1/2, ZEB1/2, CDH1/2, VIM) was analyzed by qPCR in ccRCC, sRCC-Ca, and sRCC-Sa and compared to non-neoplastic tissue and between both groups. Expression of E-cadherin, N-cadherin, vimentin and ZEB2 was analyzed using immunohistochemistry. miR-200c was downregulated in sRCC-Ca compared to ccRCC, while miR-200a was downregulated in sRCC-Sa compared to ccRCC. CDH1 was downregulated in sRCC-Sa when compared to any other group. ZEB2 was downregulated in ccRCC and sRCC compared to corresponding non-neoplastic kidney. A positive correlation was observed between CDH1 expression and miR-200a/b/c. Our results suggest that full EMT is not present in sRCC. Instead, discreet molecular differences exist between ccRCC, sRCC-Ca, and sRCC-Sa, possibly representing distinct intermediary states undergoing pEMT.

Clinical and Analytical Validation of Two Methods for Ki-67 Scoring in Formalin Fixed and Paraffin Embedded Tissue Sections of Early Breast Cancer.

Proliferation determined by Ki-67 immunohistochemistry has been proposed as a useful prognostic and predictive marker in breast cancer. However, the clinical validity of Ki-67 is questionable. In this study, Ki-67 was retrospectively evaluated by three pathologists using two methods: a visual assessment of the entire slide and a quantitative assessment of the tumour margin in 411 early-stage breast cancer patients with a median follow-up of 26.8 years. We found excellent agreement between the three pathologists for both methods. The risk of recurrence for Ki-67 was time-dependent, as the high proliferation group (Ki-67 ≥ 30%) had a higher risk of recurrence initially, but after 4.5 years the risk was higher in the low proliferation group. In estrogen receptor (ER)-positive patients, the intermediate Ki-67 group initially followed the high Ki-67 group, but eventually followed the low Ki-67 group. ER-positive pN0-1 patients with intermediate Ki-67 treated with endocrine therapy alone had a similar outcome to patients treated with chemotherapy. A cut-off value of 20% appeared to be most appropriate for distinguishing between the high and low Ki-67 groups. To summarize, a simple visual whole slide Ki-67 assessment turned out to be a reliable method for clinical decision-making in early breast cancer patients. We confirmed Ki-67 as an important prognostic and predictive biomarker.

MDM2-positive papillary sarcomatoid renal cell carcinoma: a potential diagnostic pitfall.

Sarcomatoid renal cell carcinoma is a highly aggressive form of carcinoma, histologically showing both carcinomatous and mesenchymal component in different proportions. We present a case of advanced type 1 papillary sarcomatoid renal cell carcinoma infiltrating adjacent organs and showing positivity for MDM2 by immunohistochemistry and MDM2 amplification by fluorescence in situ hybridization. This finding, together with sarcomatoid morphology, poses a potential pitfall for diagnosis with dedifferentiated liposarcoma. MDM2 is known to be altered in various human sarcomas. Only recently, MDM2 alterations have been reported in carcinomas. The presented case illustrates the need of thorough sampling with clinic-pathological correlation before making a final diagnosis in sarcomatoid retroperitoneal tumours. Additionally, the potential clinical implications of MDM2 amplification in renal cell carcinoma are discussed.

Differences in SNP genotype distributions between complex and simple suicides.

Dysregulations in serotonin neurotransmission can be a strong contributing factor in suicide and impulsive-aggressive personality traits. Victims of suicide form a heterogeneous group in terms of planning, lethality and number of used methods. In this study, we tested single nucleotide polymorphisms (SNPs) of the monoamine oxidase (MAO) A and B genes on the Slovenian population, which has one of the highest suicide rates in the world. Genotyping was performed on 77 victims of complex suicide, 406 victims of simple suicide and 289 controls. The differences in allele distribution were investigated with the two-tailed χ2 test. Haplotype analysis was performed on 740 subjects. Significant or tendency for significant differences in distribution was observed for all studied polymorphisms in the MAOA gene when comparing male victims of complex suicide, victims of simple suicide and controls. Minor allele frequencies in male victims of complex suicide were A 6.7% for rs3027407, C 13% for rs909525 and T 12.7% for rs1137070; in victims of simple suicide, A 36.3% for rs3027407, C 39.5% for rs909525 and T 36.4% for rs1137070; and in controls, A 25.2% for rs3027407, C 30.4% for rs909525 and T 25.8% for rs1137070. The distribution analysis of polymorphism rs1799836 in the MAOB gene and all studied polymorphisms in the MAOA gene in females failed to show any significant results. GTC haplotype (for rs3027407, rs909525, rs1137070) in MAOA polymorphisms was more frequent in victims of complex suicide compared to that in controls and victims of simple suicide. Compared to victims of complex suicide, male victims of simple suicide were more often carriers of MAOA alleles that are, according to literature, associated with higher levels of impulsivity and anger. These differences in SNP distribution could serve as an additional method of differentiating between victims of complex and victims of simple suicide. Further studies including psychological autopsies should be carried out in order to identify personality traits and behavioural differences among distinct groups of suicide victims.