title: Prognostic significance of multidrug-resistance protein (MDR-1) in renal clear cell carcinomas: a five year follow-up analysis.
abstract: BACKGROUND
  A large number of renal cancer patients shows poor or partial response to chemotherapy and the mechanisms have not been still understood. Multi-drug resistance is the principal mechanism by which many cancers develop resistance to chemotherapic drugs. The role of the multi-drug resistant transporter (MDR-1/P-glycoprotein), the gene product of MDR-1, and that one of the so-called multi-drug resistance associated protein (MRP), two energy-dependent efflux pumps, are commonly known to confer drug resistance. We studied MDR-1 expression in selected cases of renal cell carcinoma (RCC), clear cell type, with long-term follow-up, in order to establish its prognostic role and its possible contribution in the choice of post-surgical therapy.
  
  
  METHODS
  MDR-1 has been studied by standard LSAB-HRP immunohistochemical technique, in paraffin embedded RCC samples. Protein expression has been compared to clinical and histopathological data and to disease specific survival of RCC patients, by Kaplan-Meier curve and Cox multivariate regression analyses.
  
  
  RESULTS
  Two groups of RCCs were obtained by esteeming MDR-1 expression and disease specific survival (obtained with Kaplan-Meier curve and Cox multivariate regression analyses): the first one presents low or absent MDR-1 expression and good survival; the second one is characterized by high MDR-1 expression and significant poor outcome (p < 0.05). Afterwards, we have found disease specific survival, adjusted for stages and independent of therapy: this difference of survival rates was statistically significant (p < 0.05). Stage adjusted disease specific survival rate, according to MDR-1 expression and therapy in patients affected by RCC in early stage (stage I), has revealed that the group of patients with high MDR-1 expression and without adjuvant therapy showed poor survival (p < 0.05). Cox multivariate regression analysis has confirmed that, in our cohort of RCC (clear cell type) patients, the strong association between MDR-1 and worse outcome is independent not only of the adjuvant therapy, but also of the other prognostic parameters (p < 0.05).
  
  
  CONCLUSIONS
  In our opinion, the results of this study well prove the relationship between MDR-1 expression and worse clinical prognosis in RCC, because MDR-1 over-expressing RCCs can be considered a group of tumours with a more aggressive behavior. This finding outlines a possible role of MDR-1 as prognostic factor, dependent and independent of multidrug resistance. These results could be useful to predict cancer evolution and to choose the appropriate treatment: this is another step that can stimulate further promising and interesting investigations on broader study population.
authors.affiliation: Department of Biomorphological and Functional Sciences, Section of Pathology, University of Naples Federico II, Naples, Italy. chiara.mignogna@libero.it <chiara.mignogna@libero.it>
authors.forename: Chiara
authors.initials: C
authors.lastname: Mignogna
authors.forename: Stefania
authors.initials: S
authors.lastname: Staibano
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Altieri
authors.forename: Gaetano
authors.initials: G
authors.lastname: De Rosa
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pannone
authors.forename: Angela
authors.initials: A
authors.lastname: Santoro
authors.forename: Rosanna
authors.initials: R
authors.lastname: Zamparese
authors.forename: Massimino
authors.initials: M
authors.lastname: D'Armiento
authors.forename: Romualdo
authors.initials: R
authors.lastname: Rocchetti
authors.forename: Ernesto
authors.initials: E
authors.lastname: Mezza
authors.forename: Mario
authors.initials: M
authors.lastname: Nasti
authors.forename: Viviana
authors.initials: V
authors.lastname: Strazzullo
authors.forename: Vittorino
authors.initials: V
authors.lastname: Montanaro
authors.forename: Massimo
authors.initials: M
authors.lastname: Mascolo
authors.forename: Pantaleo
authors.initials: P
authors.lastname: Bufo
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate / Q000639:trends
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor