Somatic VHL alteration and its impact on prognosis in patients with clear cell renal cell carcinoma

  • Authors:
    • Jung Han Kim
    • Chul Won Jung
    • Yeon Hee Cho
    • Jeeyun Lee
    • Se-Hoon Lee
    • Ho Young Kim
    • Jinny Park
    • Joon-Oh Park
    • Kihyun Kim
    • Won Seog Kim
    • Young Suk Park
    • Young-Hyuck Im
    • Won Ki Kang
    • Keunchil Park
  • View Affiliations

  • Published online on: May 1, 2005     https://doi.org/10.3892/or.13.5.859
  • Pages: 859-864
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Abstract

Somatic inactivation of the von Hippel-Lindau (VHL) gene is the most frequent genetic event observed in clear cell renal cell carcinoma (CC-RCC). However, the prognostic relevance of somatic VHL alteration and its target, hypoxia inducible factor (HIF)-1α has not been defined. We investigated the genetic changes in the VHL gene and HIF-1α and studied their clinical implications in patients with sporadic CC-RCC. Patients who underwent nephrectomy were eligible if they had pathologically confirmed CC-RCC not associated with VHL disease or familial RCC. Tumor tissues were selected from paraffin blocks on the basis of hematoxylin and eosin (H&E)-stained sections. Polymerase chain reaction-single strand conformation polymorphism analysis was performed to detect VHL mutations and genetic changes in HIF-1α, which were followed by automated direct sequencing. VHL hypermethylation was examined by methylation-specific PCR. A total of 56 patients were enrolled and somatic VHL alterations were detected in 16 patients (29%); intragenic mutation in eight, hypermethylation in five, both alterations in three. The mutation types were missense in five patients, silent in three, nonsense in two, and frameshift in one. Somatic VHL alterations were not significantly associated with progression-free survival (PFS) or overall survival (OS). However, patients with 'loss-of-function' VHL mutation showed significantly decreased PFS (P=0.016) and OS (P=0.046). Although the association between VHL alteration and response to immunotherapy was not significant (P=0.486), patients with missense mutation seem to have better response to immunotherapy. The Pro582Ser change in HIF-1α was detected in six patients (11%) and was positively correlated with the development of metastases (P=0.023). This study did not show an association between somatic VHL alteration and prognosis in patients with sporadic CC-RCC. However, it suggests that the therapeutic and prognostic implication of somatic VHL alteration may be different according to the mutational subtype and that the Pro582Ser change in HIF-1α may contribute to the development of metastases.

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May 2005
Volume 13 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Kim JH, Jung CW, Cho YH, Lee J, Lee S, Kim HY, Park J, Park J, Kim K, Kim WS, Kim WS, et al: Somatic VHL alteration and its impact on prognosis in patients with clear cell renal cell carcinoma. Oncol Rep 13: 859-864, 2005
APA
Kim, J.H., Jung, C.W., Cho, Y.H., Lee, J., Lee, S., Kim, H.Y. ... Park, K. (2005). Somatic VHL alteration and its impact on prognosis in patients with clear cell renal cell carcinoma. Oncology Reports, 13, 859-864. https://doi.org/10.3892/or.13.5.859
MLA
Kim, J. H., Jung, C. W., Cho, Y. H., Lee, J., Lee, S., Kim, H. Y., Park, J., Park, J., Kim, K., Kim, W. S., Park, Y. S., Im, Y., Kang, W. K., Park, K."Somatic VHL alteration and its impact on prognosis in patients with clear cell renal cell carcinoma". Oncology Reports 13.5 (2005): 859-864.
Chicago
Kim, J. H., Jung, C. W., Cho, Y. H., Lee, J., Lee, S., Kim, H. Y., Park, J., Park, J., Kim, K., Kim, W. S., Park, Y. S., Im, Y., Kang, W. K., Park, K."Somatic VHL alteration and its impact on prognosis in patients with clear cell renal cell carcinoma". Oncology Reports 13, no. 5 (2005): 859-864. https://doi.org/10.3892/or.13.5.859