965 IMPACT OF INCREASED EXPRESSION OF GLUCOSE-REGULATED PROTEIN 78 ON CLINICOPATHOLOGICAL PARAMETERS AND PROGNOSIS IN RENAL CELL CARCINOMA

Abstract

You have accessJournal of UrologyKidney Cancer: Evaluation and Staging1 Apr 2011965 IMPACT OF INCREASED EXPRESSION OF GLUCOSE-REGULATED PROTEIN 78 ON CLINICOPATHOLOGICAL PARAMETERS AND PROGNOSIS IN RENAL CELL CARCINOMA Kenji Kuroda, Akio Horiguchi, Takako Asano, Shinsuke Tasaki, Junichi Asakuma, Hidehiko Yoshii, Akinori Sato, Keiichi Ito, Kenji Seguchi, Makoto Sumitomo, and Tomohiko Asano Kenji KurodaKenji Kuroda Tokorozawa, Saitama, Japan More articles by this author , Akio HoriguchiAkio Horiguchi Tokorozawa, Saitama, Japan More articles by this author , Takako AsanoTakako Asano Tokorozawa, Saitama, Japan More articles by this author , Shinsuke TasakiShinsuke Tasaki Tokorozawa, Saitama, Japan More articles by this author , Junichi AsakumaJunichi Asakuma Tokorozawa, Saitama, Japan More articles by this author , Hidehiko YoshiiHidehiko Yoshii Tokorozawa, Saitama, Japan More articles by this author , Akinori SatoAkinori Sato Tokorozawa, Saitama, Japan More articles by this author , Keiichi ItoKeiichi Ito Tokorozawa, Saitama, Japan More articles by this author , Kenji SeguchiKenji Seguchi Tokorozawa, Saitama, Japan More articles by this author , Makoto SumitomoMakoto Sumitomo Tokorozawa, Saitama, Japan More articles by this author , and Tomohiko AsanoTomohiko Asano Tokorozawa, Saitama, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.933AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Glucose-regulated protein 78 (GRP78) acts as a chaperone for newly formed proteins during folding and glycosylation. The regulation and expression of GRP78 are associated with resistance to apoptosis in some forms of cancer, but the impact of GRP78 expression on the progression of renal cell carcinoma (RCC) is unclear. To better understand the effects of GRP78 on tumor progression and prognosis in RCC, we assessed its expression by using primary and metastatic tumor sections from patients with RCC and then correlated our findings with clinicopathological parameters, including the patients' survival. METHODS Immunohistochemistry was performed using formalin-fixed and paraffin-embedded specimens, all from the same 128 patients: 128 primary RCC specimens (120 conventional and 8 other cell types) and 9 metastatic specimens. The determination of positive or negative staining was based on the intensity of staining and the percentage of cells stained. Correlation of GRP78 positivity with clinicopathological parameters, including the patients' survival, was evaluated. RESULTS GRP78 positivity was found in 71 of 128 (55.5%) of the primary tumors and in 8 of 9 (88.9%) specimens taken from the 9 patients with metastasis. GRP78 positivity was also found in most (7 of 8, 87.5%) of the specimens of non-conventional RCC subtypes. Statistically significant associations were found between GRP78 positivity and higher tumor grade (G3; P < 0.0001), advanced T stage (≥ pT3; P = 0.0002), pathological vascular invasion (pV1; P < 0.0001), regional nodal involvement (≥ N1; P = 0.0086), and distant metastasis at presentation (M1; P = 0.001). Positivity for GRP78 was significantly associated with shortened disease-specific survival not only in the patients with conventional RCC (P = 0.0043) but also in all the patients (P = 0.0036). Progression-free survival was also shorter in the patients with positive GRP78 than in those with negative GRP78 (P = 0.0302 for the 106 N0M0 patients with tumors of any cancer cell type, and P = 0.0165 for the 101 N0M0 patients with conventional RCC). CONCLUSIONS Our study showed that a high level of GRP78 expression might be a useful parameter for identifying poor disease-specific and progression-free survival in RCC patients. GRP78 positivity might also contribute to metastatic progression of RCC and could also be used as a marker of aggressiveness for non-conventional RCC subtypes. The findings from the present study could be helpful in the diagnostic and prognostic assessment of RCC. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e389 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kenji Kuroda Tokorozawa, Saitama, Japan More articles by this author Akio Horiguchi Tokorozawa, Saitama, Japan More articles by this author Takako Asano Tokorozawa, Saitama, Japan More articles by this author Shinsuke Tasaki Tokorozawa, Saitama, Japan More articles by this author Junichi Asakuma Tokorozawa, Saitama, Japan More articles by this author Hidehiko Yoshii Tokorozawa, Saitama, Japan More articles by this author Akinori Sato Tokorozawa, Saitama, Japan More articles by this author Keiichi Ito Tokorozawa, Saitama, Japan More articles by this author Kenji Seguchi Tokorozawa, Saitama, Japan More articles by this author Makoto Sumitomo Tokorozawa, Saitama, Japan More articles by this author Tomohiko Asano Tokorozawa, Saitama, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...