Increased BTB-Kelch type substrate adaptor protein immunoreactivity associates with advanced stage and poor differentiation in renal cell carcinoma.
Renal cell carcinoma (RCC) is a malignancy with increasing incidence. Despite the well-known prognostic factors - the stage, grade and histological subtype - the clinical course of RCC can seem quite random. The aim of this study was to evaluate markers of the oxidative system as candidate prognostic factors for RCC. Our study population consisted of 152 patients who underwent operation for RCC between 1990 and 1999. The tumours were examined with three immunohistochemical markers of the oxidative system, thioredoxin (Trx), NF-E2-related factor (Nfr2) and BTB-Kelch type substrate adaptor protein (Keap1). Cytoplasmic Keap1 staining was related to poorer prognosis in renal cancer-specific survival. The difference was statistically significant (P=0.02). Keap1 staining was associated with a more advanced stage and a higher nuclear grade. Cytoplasmic Trx staining was associated with a trend of better prognosis in renal cancer-specific survival. Nfr2 staining was not a prognostic factor in renal cancer-specific survival. In RCC, Keap1 is associated with a more advanced disease, a higher grade and a poorer prognosis.
Department of Surgery, Oulu University Hospital, Oulu, 90029 OYS, Finland.
Hanna
H
Ronkainen
Markku H
MH
Vaarala
Saila
S
Kauppila
Ylermi
Y
Soini
Timo K
TK
Paavonen
Jenni
J
Rask
Pasi
P
Hirvikoski
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D002454:Cell Differentiation; D003593:Cytoplasm / Q000737:chemistry; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis*; D053208:Kaplan-Meier Estimate; D000072019:Kelch-Like ECH-Associated Protein 1; D007680:Kidney Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D050984:NF-E2 Transcription Factor, p45 Subunit / Q000032:analysis; D009367:Neoplasm Staging; D009392:Nephrectomy; D016016:Proportional Hazards Models; D013879:Thioredoxins / Q000032:analysis; D013997:Time Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D050984:NF-E2 Transcription Factor, p45 Subunit; C494692:NFE2 protein, human; D013879:Thioredoxins