Expression of insulin-like growth factor I receptor and survival in patients with clear cell renal cell carcinoma

Alexander Parker, John C. Cheville, Christine Lohse, James R Cerhan, Michael L. Blute

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Purpose: The development of scoring systems that combine pathological and clinical characteristics of clear cell renal cell carcinoma (CC-RCC) have improved outcome prediction in patients with CC-RCC. However, these scoring systems represent surrogate markers of the underlying molecular mechanisms of tumor aggressiveness and provide no tangible targets for potential therapy. As such, there is a need to identify molecular prognostic markers and potential targets of therapy for CC-RCC. Recent studies suggest that the insulin-like growth factor-I receptor (IGF-IR) may have prognostic value for patients with CC-RCC. Materials and Methods: Using a large, clinic based cohort of 280 patients who had CC-RCC treated with radical nephrectomy, we tested the hypothesis that the immunohistochemical detection of IGF-IR expression in CC-RCC is associated with poorer cancer specific survival. Results: Kaplan-Meier analysis suggested that patients with IGF-IR positive CC-RCC experienced significantly decreased cancer specific survival than those with IGF-IR negative CC-RCC. The difference in survival was apparent within 2 years after surgery and it remained throughout followup. Based on a Cox proportional hazard model adjusting for age and sex patients with tumors that showed IGF-IR expression had a 70% increased risk of death due to CC-RCC than patients who had tumors without IGF-IR expression (HR = 1.7, 95% CI 1.2 to 2.6). The risk of CC-RCC death increased in individuals with greater than 50% IGF-IR expression (HR = 1.9, 95% CI 1.2 to 3.0). Adjustment for the Mayo Clinic Stage, Size, Grade and Necrosis Score attenuated the risk estimates but did not completely explain the association. Conclusions: Evidence from this investigation is consistent with laboratory data suggesting that IGF-IR expression is associated with CC-RCC survival and could potentially represent a molecular avenue for therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)420-424
Number of pages5
JournalJournal of Urology
Volume170
Issue number2 I
StatePublished - Aug 1 2003

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IGF Type 1 Receptor
Renal Cell Carcinoma
Survival
Neoplasms
Kaplan-Meier Estimate
Nephrectomy
Proportional Hazards Models
Cell Survival
Cell Death
Necrosis
Therapeutics
Biomarkers

Keywords

  • Carcinoma, renal cell
  • Kidney
  • Nephrectomy
  • Receptors, somatomedin
  • Survival rate

ASJC Scopus subject areas

  • Urology

Cite this

Expression of insulin-like growth factor I receptor and survival in patients with clear cell renal cell carcinoma. / Parker, Alexander; Cheville, John C.; Lohse, Christine; Cerhan, James R; Blute, Michael L.

In: Journal of Urology, Vol. 170, No. 2 I, 01.08.2003, p. 420-424.

Research output: Contribution to journalArticle

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abstract = "Purpose: The development of scoring systems that combine pathological and clinical characteristics of clear cell renal cell carcinoma (CC-RCC) have improved outcome prediction in patients with CC-RCC. However, these scoring systems represent surrogate markers of the underlying molecular mechanisms of tumor aggressiveness and provide no tangible targets for potential therapy. As such, there is a need to identify molecular prognostic markers and potential targets of therapy for CC-RCC. Recent studies suggest that the insulin-like growth factor-I receptor (IGF-IR) may have prognostic value for patients with CC-RCC. Materials and Methods: Using a large, clinic based cohort of 280 patients who had CC-RCC treated with radical nephrectomy, we tested the hypothesis that the immunohistochemical detection of IGF-IR expression in CC-RCC is associated with poorer cancer specific survival. Results: Kaplan-Meier analysis suggested that patients with IGF-IR positive CC-RCC experienced significantly decreased cancer specific survival than those with IGF-IR negative CC-RCC. The difference in survival was apparent within 2 years after surgery and it remained throughout followup. Based on a Cox proportional hazard model adjusting for age and sex patients with tumors that showed IGF-IR expression had a 70{\%} increased risk of death due to CC-RCC than patients who had tumors without IGF-IR expression (HR = 1.7, 95{\%} CI 1.2 to 2.6). The risk of CC-RCC death increased in individuals with greater than 50{\%} IGF-IR expression (HR = 1.9, 95{\%} CI 1.2 to 3.0). Adjustment for the Mayo Clinic Stage, Size, Grade and Necrosis Score attenuated the risk estimates but did not completely explain the association. Conclusions: Evidence from this investigation is consistent with laboratory data suggesting that IGF-IR expression is associated with CC-RCC survival and could potentially represent a molecular avenue for therapeutic intervention.",
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T1 - Expression of insulin-like growth factor I receptor and survival in patients with clear cell renal cell carcinoma

AU - Parker, Alexander

AU - Cheville, John C.

AU - Lohse, Christine

AU - Cerhan, James R

AU - Blute, Michael L.

PY - 2003/8/1

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N2 - Purpose: The development of scoring systems that combine pathological and clinical characteristics of clear cell renal cell carcinoma (CC-RCC) have improved outcome prediction in patients with CC-RCC. However, these scoring systems represent surrogate markers of the underlying molecular mechanisms of tumor aggressiveness and provide no tangible targets for potential therapy. As such, there is a need to identify molecular prognostic markers and potential targets of therapy for CC-RCC. Recent studies suggest that the insulin-like growth factor-I receptor (IGF-IR) may have prognostic value for patients with CC-RCC. Materials and Methods: Using a large, clinic based cohort of 280 patients who had CC-RCC treated with radical nephrectomy, we tested the hypothesis that the immunohistochemical detection of IGF-IR expression in CC-RCC is associated with poorer cancer specific survival. Results: Kaplan-Meier analysis suggested that patients with IGF-IR positive CC-RCC experienced significantly decreased cancer specific survival than those with IGF-IR negative CC-RCC. The difference in survival was apparent within 2 years after surgery and it remained throughout followup. Based on a Cox proportional hazard model adjusting for age and sex patients with tumors that showed IGF-IR expression had a 70% increased risk of death due to CC-RCC than patients who had tumors without IGF-IR expression (HR = 1.7, 95% CI 1.2 to 2.6). The risk of CC-RCC death increased in individuals with greater than 50% IGF-IR expression (HR = 1.9, 95% CI 1.2 to 3.0). Adjustment for the Mayo Clinic Stage, Size, Grade and Necrosis Score attenuated the risk estimates but did not completely explain the association. Conclusions: Evidence from this investigation is consistent with laboratory data suggesting that IGF-IR expression is associated with CC-RCC survival and could potentially represent a molecular avenue for therapeutic intervention.

AB - Purpose: The development of scoring systems that combine pathological and clinical characteristics of clear cell renal cell carcinoma (CC-RCC) have improved outcome prediction in patients with CC-RCC. However, these scoring systems represent surrogate markers of the underlying molecular mechanisms of tumor aggressiveness and provide no tangible targets for potential therapy. As such, there is a need to identify molecular prognostic markers and potential targets of therapy for CC-RCC. Recent studies suggest that the insulin-like growth factor-I receptor (IGF-IR) may have prognostic value for patients with CC-RCC. Materials and Methods: Using a large, clinic based cohort of 280 patients who had CC-RCC treated with radical nephrectomy, we tested the hypothesis that the immunohistochemical detection of IGF-IR expression in CC-RCC is associated with poorer cancer specific survival. Results: Kaplan-Meier analysis suggested that patients with IGF-IR positive CC-RCC experienced significantly decreased cancer specific survival than those with IGF-IR negative CC-RCC. The difference in survival was apparent within 2 years after surgery and it remained throughout followup. Based on a Cox proportional hazard model adjusting for age and sex patients with tumors that showed IGF-IR expression had a 70% increased risk of death due to CC-RCC than patients who had tumors without IGF-IR expression (HR = 1.7, 95% CI 1.2 to 2.6). The risk of CC-RCC death increased in individuals with greater than 50% IGF-IR expression (HR = 1.9, 95% CI 1.2 to 3.0). Adjustment for the Mayo Clinic Stage, Size, Grade and Necrosis Score attenuated the risk estimates but did not completely explain the association. Conclusions: Evidence from this investigation is consistent with laboratory data suggesting that IGF-IR expression is associated with CC-RCC survival and could potentially represent a molecular avenue for therapeutic intervention.

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KW - Receptors, somatomedin

KW - Survival rate

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