Prognostic impact of the expression of ALDH1 and SOX2 in urothelial cancer of the upper urinary tract.

Abstract

Aldehyde dehydrogenase 1 (ALDH1) and sex determining region-Y-related high mobility group box 2 (SOX2) have been identified as putative cancer stem-like cell/tumor-initiating cell markers in various cancer tissues. The aim of this study was to elucidate the prognostic impact of these putative cancer stem-like cell/tumor-initiating cell markers in upper urinary tract urothelial cell carcinoma. Immunohistochemical staining for ALDH1 and SOX2 was carried out on archival specimens from 125 patients with upper urinary tract urothelial cell carcinoma who underwent radical nephroureterectomy. The prognostic value of ALDH1 and SOX2 expression and other clinicopathological features was evaluated. On univariate analysis, tumor grade, pathological T stage, pathological N stage, lymphovascular invasion, ALDH1 expression and SOX2 expression were associated with a poor prognosis. On multivariate analysis, the independent factors of prognosis were tumor grade (P=0.014), pathological N stage (P=0.005) and ALDH1 expression (P=0.002). In subgroup analysis, those subgroups with no positive, one positive or two positive results in immunohistochemistry for ALDH1 and SOX2 expression had estimated 5-year cancer-specific survival rates of 80%, 49% and 22%, respectively (P<0.001). Neither ALDH1 nor SOX2 expression correlated with intravesical recurrence after radical nephroureterectomy. These findings suggest that cancer stem-like cells/tumor-initiating cells are linked to more aggressive behavior of upper urinary tract urothelial cell carcinoma, supporting the current cancer stem cell hypothesis. Thus, therapeutic targeting of cancer stem-like cells/tumor-initiating cells in upper urinary tract urothelial cell carcinoma is a future possibility.

• Authors: Hiroshi Kitamura, Toshihiko Torigoe, Yoshihiko Hirohashi, Hiroko Asanuma, Ryuta Inoue, Sachiyo Nishida, Toshiaki Tanaka, Fumimasa Fukuta, Naoya Masumori, Noriyuki Sato, Taiji Tsukamoto
• Journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (Mod Pathol) Vol. 26 Issue 1 Pg. 117-24 (Jan 2013) ISSN: 1530-0285 [Electronic] United States
• PMID: 22899292 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• Isoenzymes
• SOX2 protein, human
• SOXB1 Transcription Factors
• Aldehyde Dehydrogenase 1 Family
• ALDH1A1 protein, human
• Retinal Dehydrogenase

Topics

• Adult
• Aged
• Aged, 80 and over
• Aldehyde Dehydrogenase 1 Family
• Biomarkers, Tumor (analysis)
• Carcinoma, Transitional Cell (metabolism, mortality, pathology)
• Disease-Free Survival
• Female
• Humans
• Immunohistochemistry
• Isoenzymes (analysis, biosynthesis)
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Neoplasm Staging
• Neoplastic Stem Cells (metabolism)
• Prognosis
• Proportional Hazards Models
• Retinal Dehydrogenase (analysis, biosynthesis)
• SOXB1 Transcription Factors (analysis, biosynthesis)
• Urologic Neoplasms (metabolism, mortality, pathology)