Nuclear EGFR characterize still controlled proliferation retained in better differentiated clear cell RCC

Figure Legend: Nuclear EGFR is visible in the low grade part of clear cell RCC (arrow), while large, irregular nuclei are negative (asterix), 200x.

Acknowledgement: We thank our statistician Prof. Ivan Dražić (Department of Mathematics, Faculty of Engineering, University of Rijeka) for expert assistance in the statistical analysis of this study.

About the author

Gordana Đorđević-pathologist and associated professor at the Department of Pathology, School of Medicine, University of Rijeka and Clinical Hospital Centre of Rijeka, Croatia. Main activities and responsibilities in my daily practice are Uropathology and Nephropathology. Special interest in renal cell carcinoma research has led to collaboration with colleagues of different specialties as follows:

Ahel ,Urologist, Dr. med. Department of Urology, Clinical Hospital Centre Rijeka.
Markic, ass. prof., urologist, Department of Urology, Clinical Hospital Centre Rijeka
Mozetic , ass. prof., urologist, Medico Polyclinic, Rijeka.
Spanjol , ass. prof., urologist, Department of Urology, Clinical Hospital Centre Rijeka
Grahovac, prof, Department of molecular biology, Department of Pathology, School of Medicine, University of Rijeka
Stifter, assoc. prof. ; Department of Pathology, School of Medicine, University of Rijeka

Journal Reference

Med Hypotheses. 2015;85(2):183-5.

Ahel ¹, G. Dordevic ² D. Markic¹, V. Mozetic ³, J. Spanjol ¹, B. Grahovac ², S. Stifter ²

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Department of Urology, Clinical Hospital Centre Rijeka, Krešimirova 42, 51000 Rijeka, Croatia
Department of Pathology, School of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia
Medico Polyclinic, Agatićeva 8, 51000 Rijeka, Croatia

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Abstract

Renal cell carcinoma (RCC) is the most common solid kidney tumor representing 2–3% of all cancers, with the highest frequency occurring in Western countries. There was a worldwide and European annual increase in incidence of approximately 2% although incidence has been stabilized in last few years. One third of the patients already have metastases in the time of the diagnosis with poor prognosis because renal cell carcinoma are radio and chemoresistant. The prognostic value of EGFR over-expression in renal cell carcinoma is a controversial issue that could be explained by different histological types of study tumors and non-standardized criteria for evaluation of expression. Recent evidences points to a new mode of EGFR signaling pathway in which activated EGFR undergoes nuclear translocalization and then, as transcription factor, mediates gene expression and other cellular events required for highly proliferating activities. According to our observations, the membranous expression of EGFR associates with high nuclear grade and poor differentiated tumors. On the other hand, nuclear EGFR expression was high in low nuclear graded and well differentiated tumors with good prognosis. We hypothesize that this mode of EGFR signaling characterizes still controlled proliferation retained in well differentiated renal cell carcinoma. From a practical point of view, EGFR immunohistochemical localization can be useful in preselection of patients who could potentially benefit of EGFR targeting therapy.

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