Expression of endothelin 2 and localized clear cell renal cell carcinoma

Brian M. Bot, Jeanette E Eckel-Passow, Shauna N. Legrand, Tracy Hilton, John C. Cheville, Todd Igel, Alexander Parker

Research output: Contribution to journalArticle

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Abstract

Despite the rising incidence of clear cell renal cell carcinoma, the molecular events that support its development and progression remain unclear. Herein, we evaluate the association of endothelin 2 expression with both clear cell renal cell carcinoma development and progression-free survival. We conducted real-time polymerase chain reaction to determine endothelin 2 expression levels on 238 patients who underwent nephrectomy for localized clear cell renal cell carcinoma, 161 of whom also had adjacent normal kidney samples available for analysis. To evaluate associations with clear cell renal cell carcinoma development, linear mixed models were used to compare differential expression between tumor and a normal kidney as well as to explore interactions with clinicopathologic features. To evaluate associations with prognosis, Cox proportional hazards models were used to assess the association of progression-free survival and endothelin 2 expression in tumor tissue. Overall, endothelin 2 expression was higher in tumor samples versus patient-matched normal kidney samples, with an average fold change of 1.99 (95% confidence interval, 1.48-2.60; P <.0001). This overexpression in tumor versus normal kidney samples was more pronounced in low- compared with high-grade tumors (interaction, P =.0002), in early- compared with late-stage tumors (interaction, P =.001), and in tumors without compared with those with necrosis (interaction, P =.001). Moreover, an increasing endothelin 2 expression in tumors was associated with a longer progression-free survival (hazard ratio, 0.89; 95% confidence interval, 0.80-0.99; P =.03); however, after controlling for known clinicopathologic factors, this association was attenuated (hazard ratio, 0.99; 95% confidence interval, 0.89-1.09; P =.7). Up-regulation of endothelin 2 is a common and early event in localized clear cell renal cell carcinoma. Higher tumor expression of endothelin 2 is associated with a longer progression-free survival but not after adjustment for well-known pathologic indices. Thus, although endothelin 2 does not appear to be an independent prognostic marker, there is evidence of a putative role in clear cell renal cell carcinoma progression. If supportive mechanistic data can be produced, endothelin 2 could represent a potential target for chemopreventive or neoadjuvant therapeutics for clear cell renal cell carcinoma.

Original languageEnglish (US)
Pages (from-to)843-849
Number of pages7
JournalHuman Pathology
Volume43
Issue number6
DOIs
StatePublished - Jun 2012

Fingerprint

Endothelin-2
Renal Cell Carcinoma
Neoplasms
Disease-Free Survival
Kidney
Confidence Intervals
Nephrectomy
Proportional Hazards Models
Real-Time Polymerase Chain Reaction
Linear Models
Necrosis
Up-Regulation

Keywords

  • Biomarker
  • Early event
  • Endothelin 2
  • Kidney cancer
  • Overexpression

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Expression of endothelin 2 and localized clear cell renal cell carcinoma. / Bot, Brian M.; Eckel-Passow, Jeanette E; Legrand, Shauna N.; Hilton, Tracy; Cheville, John C.; Igel, Todd; Parker, Alexander.

In: Human Pathology, Vol. 43, No. 6, 06.2012, p. 843-849.

Research output: Contribution to journalArticle

Bot, Brian M. ; Eckel-Passow, Jeanette E ; Legrand, Shauna N. ; Hilton, Tracy ; Cheville, John C. ; Igel, Todd ; Parker, Alexander. / Expression of endothelin 2 and localized clear cell renal cell carcinoma. In: Human Pathology. 2012 ; Vol. 43, No. 6. pp. 843-849.
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