title: Is there any potential link among caspase-8, p-p38 MAPK and bcl-2 in clear cell renal cell carcinomas? A comparative immunohistochemical analysis with clinical connotations.
abstract: BACKGROUND
  Clear cell renal cell carcinomas (ccRCCs) constitute the most common renal carcinomas, characterized by a relatively aggressive clinical course. Thus, scientific research is targeting towards the identification of immunohistochemical and molecular markers that could be useful regarding diagnosis, appropriate therapy and prediction of prognosis. In the present study we assessed and correlated the expression of caspase-8, phosphorylated p38 mitogen-activated protein kinase (p-p38) and bcl-2 protein with histopathological features and clinical outcome of 27 patients with ccRCCs.
  
  
  METHODS
  Immunohistochemistry in formalin-fixed and paraffin-embedded tissue sections was performed. The associations among various features were assessed utilizing statistical analysis.
  
  
  RESULTS
  We found that increased expression of cytoplasmic caspase-8 and bcl-2 protein was strongly associated with low Fuhrman's grade of carcinomas (p = 0.019 and p = 0.041, respectively). On the other hand, increased p-p38 expression was significantly related to high Fuhrman's grade (p = 0.006). Moreover, high bcl-2 expression was correlated with low pathological stage of ccRCCs (p = 0.026). Increased expression of cytoplasmic caspase-8 as well as low-grade tumors (grade 1 and 2) implied a greater probability of patients' survival, in univariate statistical analysis (p = 0.037 and p = 0.019, respectively). Neither p-p38 nor bcl-2 expression was significantly linked to patients' survival. There were not emerged statistically significant associations among caspase-8, p-p38 kinase and bcl-2 protein.
  
  
  CONCLUSIONS
  For the first time the prognostic impact of caspase-8 and p-p38 was studied in a series of ccRCCs, using immunohistochemistry in formalin-fixed and paraffin-embedded tissue sections. The suggestive relationship of caspase-8 with patients' clinical outcome, as well as the role of p-p38 within different grade categories, mandates further studies in larger cohorts of RCCs.
authors.affiliation: Department of Pathology, Hellenic Red Cross Hospital, Athens, Greece. vassilissamaras@yahoo.gr
authors.forename: Vassilis
authors.initials: V
authors.lastname: Samaras
authors.forename: Maria
authors.initials: M
authors.lastname: Tsopanomichalou
authors.forename: Angeliki
authors.initials: A
authors.lastname: Stamatelli
authors.forename: Christos
authors.initials: C
authors.lastname: Arnaoutoglou
authors.forename: Efstathios
authors.initials: E
authors.lastname: Samaras
authors.forename: Marianthi
authors.initials: M
authors.lastname: Arnaoutoglou
authors.forename: Hercules
authors.initials: H
authors.lastname: Poulias
authors.forename: Calypso
authors.initials: C
authors.lastname: Barbatis