Elsevier

Medical Hypotheses

Volume 85, Issue 2, August 2015, Pages 183-185
Medical Hypotheses

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

https://doi.org/10.1016/j.mehy.2015.04.033Get rights and content

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 RCC are radio and chemoresistant. The prognostic value of EGFR over-expression in RCC 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 RCC with Furhman nuclear grade I or II.

Section snippets

Introduction/background

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 [1]. One third of the patients already have metastases in the time of the diagnosis with poor prognosis because RCC are radioresistant [2] and more than 80% are chemoresistant [3]. Among alternative

The Hypothesis/theory

In our current study 135 clear cell RCC were analyzed in a tissue microarray format using immunohistochemistry aiming to compare compartmentalization of EGFR expression in tumor cells. An interesting observation emerging during research was that the membranous expression of EGFR associates with high nuclear grade in poorly differentiated tumors. On the other hand, nuclear EGFR expression was high in low nuclear graded well differentiated tumors with good overall prognosis. We hypothesize that

Consequences of the hypothesis and discussion

RCC is a heterogeneous disease regarding EGFR expression and expressed in a large proportion of clear cell carcinomas. Since, clear cell RCC is the most frequent histological variant and is the most commonly found in patients with metastatic disease it is mandatory to explore the association of the EGFR pathways with progression of tumor variant [19], [20]. Although there are mounting evidence that personalized therapy with applying targeted agents can often induce responses in patients we are

Conflict of interest statement

None.

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