Introduction & Objectives: Intracapsular conventional renal cell carcinomas (cc-RCCs) have an overall excellent prognosis and the TNM 2002 classification represents a valid prognostic system; however, additional prognostic factors are necessary to further improve the prediction of intracapsular tumor aggressiveness. Inactivation of the Von Hippel¬Lindau gene (VHL) represents the most frequent genomic abnormality in cc-RCC. The VHL product (pVHL), via a heterotrimeric complex, binds the hypoxia-inducible factor-1alfa (HIF-1 α) promoting its proteosomal degradation. Few large studies have been designed to investigate the pVHL and HIF-1α expression pattern in cc-RCC as well as their prognostic relevance. Material & Methods: Tissue microarrays were constructed from 136 intracapsular cc-RCC cases with a mean follow up of 74 months. Two commercially available monoclonal pVHL antibodies (clone Ig32 and clone Ig33) and a policlonal anti-HIF-1 α antibody were used. The expression pattern of the markers was matched with well-known clinicopathological variables and with tumor-specific survival (TSS). Results: Ig32 and Ig33 pVHL antibodies showed cytoplasmic positivity in 89.7% and 85.7% of cases, respectively. There was cytoplasmic and nuclear HIF-1α staining in 90.5% and 67.4%, respectively. The pVHL negativity and HIF-lα nuclear positivity significantly correlated with shorter TSS. In the multivariate analysis both pVHL negativity and HIF- lα nuclear expression were independent predictors of TSS. Conclusions: pVHL was expressed in most intracapsular cc-RCC at the cytoplasmic level and its lack of expression correlates with a shorter TSS. HIF- lα is expressed at both cytoplasmic and nuclear level, and nuclear HIF- lα expression significantly correlates with a shorter survival. HIF-lα nuclear—cytoplasmic trafficking seems to be important for the progression of cc-RCC. Both markers are independent prognostic factors and should be routinely used in assessing the prognosis of cc-RCC
NUCLEAR EXPRESSION OF HYPOXIA-INDUCIBLE FACTOR-1a: A UNFAVORABLE INDEPENDENT PROGNOSTIC FACTOR IN INTRACAPSULAR CONVENTIONAL CLEAR CELL RENAL CELL CARCINOMA / Minervini A., Di Cristofano C., Serni S., Menicagli M.s, Salinitri G., Pefanis G., Masieri L., Collecchi P., Bevilacqua G., Lapini A., Cavazzana A., Minervini R., Carini M.. - In: EUROPEAN UROLOGY. - ISSN 1828-6569. - STAMPA. - 6:(2007), pp. 165-165. (Annual EAU Congress Berlino 21-24 marzo).
NUCLEAR EXPRESSION OF HYPOXIA-INDUCIBLE FACTOR-1a: A UNFAVORABLE INDEPENDENT PROGNOSTIC FACTOR IN INTRACAPSULAR CONVENTIONAL CLEAR CELL RENAL CELL CARCINOMA
MINERVINI, ANDREA;Serni S.;Masieri L.;CARINI, MARCO
2007
Abstract
Introduction & Objectives: Intracapsular conventional renal cell carcinomas (cc-RCCs) have an overall excellent prognosis and the TNM 2002 classification represents a valid prognostic system; however, additional prognostic factors are necessary to further improve the prediction of intracapsular tumor aggressiveness. Inactivation of the Von Hippel¬Lindau gene (VHL) represents the most frequent genomic abnormality in cc-RCC. The VHL product (pVHL), via a heterotrimeric complex, binds the hypoxia-inducible factor-1alfa (HIF-1 α) promoting its proteosomal degradation. Few large studies have been designed to investigate the pVHL and HIF-1α expression pattern in cc-RCC as well as their prognostic relevance. Material & Methods: Tissue microarrays were constructed from 136 intracapsular cc-RCC cases with a mean follow up of 74 months. Two commercially available monoclonal pVHL antibodies (clone Ig32 and clone Ig33) and a policlonal anti-HIF-1 α antibody were used. The expression pattern of the markers was matched with well-known clinicopathological variables and with tumor-specific survival (TSS). Results: Ig32 and Ig33 pVHL antibodies showed cytoplasmic positivity in 89.7% and 85.7% of cases, respectively. There was cytoplasmic and nuclear HIF-1α staining in 90.5% and 67.4%, respectively. The pVHL negativity and HIF-lα nuclear positivity significantly correlated with shorter TSS. In the multivariate analysis both pVHL negativity and HIF- lα nuclear expression were independent predictors of TSS. Conclusions: pVHL was expressed in most intracapsular cc-RCC at the cytoplasmic level and its lack of expression correlates with a shorter TSS. HIF- lα is expressed at both cytoplasmic and nuclear level, and nuclear HIF- lα expression significantly correlates with a shorter survival. HIF-lα nuclear—cytoplasmic trafficking seems to be important for the progression of cc-RCC. Both markers are independent prognostic factors and should be routinely used in assessing the prognosis of cc-RCC
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