SLUG and SNAIL as Potential Immunohistochemical Biomarkers for Renal Cancer Staging and Survival

Author:

Zivotic Maja1,Kovacevic Sanjin2ORCID,Nikolic Gorana1ORCID,Mioljevic Ana1,Filipovic Isidora1,Djordjevic Marija3,Jovicic Vladimir4,Topalovic Nikola5,Ilic Kristina1,Radojevic Skodric Sanja1,Dundjerovic Dusko1,Nesovic Ostojic Jelena2ORCID

Affiliation:

1. Institute of Pathology, Faculty of Medicine, University of Belgrade, 1 Dr. Subotic Street, 11000 Belgrade, Serbia

2. Department of Pathological Physiology, Faculty of Medicine, University of Belgrade, 9 Dr. Subotic Street, 11000 Belgrade, Serbia

3. Faculty of Organization Sciences, University of Belgrade, 11010 Belgrade, Serbia

4. Clinic for Cardiac Surgery, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia

5. Department of Medical Physiology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia

Abstract

Renal cell carcinoma (RCC) is the deadliest urological neoplasm. Up to date, no validated biomarkers are included in clinical guidelines for the screening and follow up of patients suffering from RCC. Slug (Snail2) and Snail (Snail1) belong to the Snail superfamily of zinc finger transcriptional factors that take part in the epithelial–mesenchymal transition, a process important during embryogenesis but also involved in tumor progression. We examined Slug and Snail immunohistochemical expression in patients with different stages of renal cell carcinomas with the aim to investigate their potential role as staging and prognostic factors. A total of 166 samples of malignant renal cell neoplasms were analyzed using tissue microarray and immunohistochemistry. Slug and Snail expressions were evaluated qualitatively (presence or absence), in nuclear and cytoplasmic cell compartments and compared in relation to clinical parameters. The Kaplan–Meier survival analysis showed the impact of the sarcomatoid component and Slug expression on the survival longevity. Cox regression analysis separated Slug as the only independent prognostic factor (p = 0.046). The expression of Snail was associated with higher stages of the disease (p = 0.004), especially observing nuclear Snail expression (p < 0.001). All of the tumors that had metastasized showed nuclear immunoreactivity (p < 0.001). In clear cell RCC, we showed a significant relationship between a high nuclear grade and nuclear Snail expression (p = 0.039). Our results suggest that Slug and Snail could be useful immunohistochemical markers for staging and prognosis in patients suffering from various RCCs, representing potential targets for further therapy strategies of renal cancer.

Funder

Ministry of Education and Science of the Republic of Serbia

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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