Relevance of nuclear and cytoplasmic von Hippel Lindau protein expression for renal carcinoma progression

Peter Schraml, Alexander Hergovitz, Florian Hatz, Mahul Amin, So D. Lim, Wilhelm Krek, Michael J. Mihatsch, Holger Moch

Research output: Contribution to journalArticle

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Abstract

Alterations of the von Hippel-Lindau tumor-suppressor gene (VHL) on 3p25-p26 are frequent in clear-cell renal-cell carcinoma (RCC). The VHL protein (pVHL) is implicated in cell-cycle control and gene regulation, and requires transcription-dependent nuclear-cytoplasmic trafficking for its function. There are two biologically active VHL protein isoforms: pVHL30 and pVHL19. To study prevalence, subcellular expression and biological significance of pVHL in renal tumors, tissue microarrays with renal-cell carcinomas were immunohistochemically examined for pVHL expression. Antibodies against both protein isoforms (anti-pVHL30/pVHL19) and against pVHL30, (anti-pVHL30; Ig33) were used. The anti-pVHL30/pVHL19 antibody showed nuclear and cytoplasmic pVHL expression, whereas the anti-pVHL30 antibody (Ig33) detected cytoplasmic pVHL expression, suggesting that the distribution of VHL protein isoforms varies in the nuclear and cytoplasmic compartments of renal tumors. There were 175 of 398 primary clear-cell RCCs (44%) with both nuclear and cytoplasmic pVHL expression. Seventy-seven clear-cell RCCs (19%) showed only nuclear, 22 (6%) showed only cytoplasmic, and 124 tumors (31%) showed no pVHL, expression. Notably, combined nuclear and cytoplasmic pVHL expression was associated with low histological grade (P < 0.0001), early tumor stage (P < 0.011), and better prognosis (P < 0.01). These results imply that alteration of subcellular pVHL trafficking is of potential relevance for the biological behavior of clear-cell RCC.

Original languageEnglish (US)
Pages (from-to)1013-1020
Number of pages8
JournalAmerican Journal of Pathology
Volume163
Issue number3
DOIs
StatePublished - Sep 1 2003
Externally publishedYes

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Renal Cell Carcinoma
Carcinoma
Kidney
Protein Isoforms
Neoplasms
Proteins
cdc Genes
Antibodies
Cell Cycle Checkpoints
Tumor Suppressor Genes
Anti-Idiotypic Antibodies
Cross-Sectional Studies
Clear-cell metastatic renal cell carcinoma

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Relevance of nuclear and cytoplasmic von Hippel Lindau protein expression for renal carcinoma progression. / Schraml, Peter; Hergovitz, Alexander; Hatz, Florian; Amin, Mahul; Lim, So D.; Krek, Wilhelm; Mihatsch, Michael J.; Moch, Holger.

In: American Journal of Pathology, Vol. 163, No. 3, 01.09.2003, p. 1013-1020.

Research output: Contribution to journalArticle

Schraml, Peter ; Hergovitz, Alexander ; Hatz, Florian ; Amin, Mahul ; Lim, So D. ; Krek, Wilhelm ; Mihatsch, Michael J. ; Moch, Holger. / Relevance of nuclear and cytoplasmic von Hippel Lindau protein expression for renal carcinoma progression. In: American Journal of Pathology. 2003 ; Vol. 163, No. 3. pp. 1013-1020.
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abstract = "Alterations of the von Hippel-Lindau tumor-suppressor gene (VHL) on 3p25-p26 are frequent in clear-cell renal-cell carcinoma (RCC). The VHL protein (pVHL) is implicated in cell-cycle control and gene regulation, and requires transcription-dependent nuclear-cytoplasmic trafficking for its function. There are two biologically active VHL protein isoforms: pVHL30 and pVHL19. To study prevalence, subcellular expression and biological significance of pVHL in renal tumors, tissue microarrays with renal-cell carcinomas were immunohistochemically examined for pVHL expression. Antibodies against both protein isoforms (anti-pVHL30/pVHL19) and against pVHL30, (anti-pVHL30; Ig33) were used. The anti-pVHL30/pVHL19 antibody showed nuclear and cytoplasmic pVHL expression, whereas the anti-pVHL30 antibody (Ig33) detected cytoplasmic pVHL expression, suggesting that the distribution of VHL protein isoforms varies in the nuclear and cytoplasmic compartments of renal tumors. There were 175 of 398 primary clear-cell RCCs (44{\%}) with both nuclear and cytoplasmic pVHL expression. Seventy-seven clear-cell RCCs (19{\%}) showed only nuclear, 22 (6{\%}) showed only cytoplasmic, and 124 tumors (31{\%}) showed no pVHL, expression. Notably, combined nuclear and cytoplasmic pVHL expression was associated with low histological grade (P < 0.0001), early tumor stage (P < 0.011), and better prognosis (P < 0.01). These results imply that alteration of subcellular pVHL trafficking is of potential relevance for the biological behavior of clear-cell RCC.",
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AU - Lim, So D.

AU - Krek, Wilhelm

AU - Mihatsch, Michael J.

AU - Moch, Holger

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AB - Alterations of the von Hippel-Lindau tumor-suppressor gene (VHL) on 3p25-p26 are frequent in clear-cell renal-cell carcinoma (RCC). The VHL protein (pVHL) is implicated in cell-cycle control and gene regulation, and requires transcription-dependent nuclear-cytoplasmic trafficking for its function. There are two biologically active VHL protein isoforms: pVHL30 and pVHL19. To study prevalence, subcellular expression and biological significance of pVHL in renal tumors, tissue microarrays with renal-cell carcinomas were immunohistochemically examined for pVHL expression. Antibodies against both protein isoforms (anti-pVHL30/pVHL19) and against pVHL30, (anti-pVHL30; Ig33) were used. The anti-pVHL30/pVHL19 antibody showed nuclear and cytoplasmic pVHL expression, whereas the anti-pVHL30 antibody (Ig33) detected cytoplasmic pVHL expression, suggesting that the distribution of VHL protein isoforms varies in the nuclear and cytoplasmic compartments of renal tumors. There were 175 of 398 primary clear-cell RCCs (44%) with both nuclear and cytoplasmic pVHL expression. Seventy-seven clear-cell RCCs (19%) showed only nuclear, 22 (6%) showed only cytoplasmic, and 124 tumors (31%) showed no pVHL, expression. Notably, combined nuclear and cytoplasmic pVHL expression was associated with low histological grade (P < 0.0001), early tumor stage (P < 0.011), and better prognosis (P < 0.01). These results imply that alteration of subcellular pVHL trafficking is of potential relevance for the biological behavior of clear-cell RCC.

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