ABSTRACT
Background: Clear cell renal cell carcinoma (ccRCC) is considered the most common histopathological subtype and
constituting nearly 70% of all primary renal cell carcinomas. Dysregulation of proteins related to Renin-Angiotensin
System (RAS) could offer a new prognostic indicator in this malignant neoplasm.
Objective: This study aimed to demonstrate renin (REN) & erythropoietin (EPO) immunohistochemical expression in
ccRCC cases & their expression was correlated with the clinicopathological data & survival of the studied cases to
explore their potential prognostic role.
Material and methods: This retrospective research carried upon 30 cases ccRCC immunohistochemically stained with
REN and EPO & the results to be correlated with different clinicopathological variables and patient's survival.
Results: REN & EPO were expressed in 70% & 80% of ccRCC cases, respectively. Positive REN expression was
significantly related to younger patients' age, lower nuclear grade, absence of (renal vein thrombosis, necrosis, perirenal
fat invasion, renal sinus invasion, lymph/vascular invasion, lymph node metastasis & distant metastasis) and lower
American Joint Committee on Cancer (AJCC)stage. While EPO positive expression was significantly related to younger
patients' age, greater grade, greater T stage & higher AJCC stage. Negative REN & positive EPO expression were
correlated to poor 5-year overall survival (P= 0.008 & 0.045 respectively) & disease-free survival (P= 0.006 & 0.038
respectively).
Conclusion: Renin and Erythropoietin expression may be prognostic indicators of ccRCC and could predict patient’s
survival. Further researches are recommended to declare prognostic significance of other proteins of RAS pathway
providing new insights and treatment modalities of ccRCC.
Keywords: Renin, Erythropoietin, ccRCC.
INTRODUCTION
Renal cell carcinoma (RCC) is considered one
of the most diagnosed tumors globally with an
estimated 434,419 new cases diagnosed in 2022,
accounting for 2.2% of all cancer diagnoses worldwide
(1). Clear cell renal cell carcinoma (ccRCC) is
considered the most frequent subtype of primary RCCs
and constitutes nearly 70% of all renal cell carcinomas
(2)
. In Egypt, renal cancer ranks the 14th, and accounts
for 1.5% of all cancer diagnoses at a rate of 3.0/100,000
in men and 2/100,000 in women according to
GLOBOCAN 2022 (1). Egypt is one of countries that
had the highest mortality rates in Africa with mortality
risk 1% in this cancer (3)
.
However the incidence of RCC has been
gradually rising and there is a slight increase in the last
10 years, the mortality rates have decreased. An
increase in the number of unintentional abdominal
imaging diagnosis and the enhancements in methods of
treatment may explain the declining in mortality rate(4)
.
Recently, several studies have searched for new
prognostic markers in RCC specially clear cell type,
which is the most prevalent subtype intending to
discover a valuable predictive value in this lethal
disease. The renin angiotensin system (RAS) is known
as a poly peptide-based system that has hormonal axes
and has an eminent role in regulation of blood pressure
and maintenance of fluid balance. Dysregulation of the
RAS system has been demonstrated by several studies
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