Loss of CD44 and SOX2 expression is correlated with a poor prognosis in esophageal adenocarcinoma patients.
BACKGROUND
It has been suggested that markers associated with cancer stem cells (CSC) may play a role in esophageal cancer. Our aim was to investigate the expression pattern of proposed CSC markers ALDH1, Axin2, BMI1, CD44, and SOX2 in esophageal adenocarcinoma (EAC) and to relate their expression to survival.


METHODS
In this study we included 94 EAC patients and examined the expression of the above-mentioned markers by using immunohistochemistry on tissue microarrays. Expression was scored as positive or negative or categorized as low or high in terms of an immunoreactivity score (IRS). Expression rates were related to clinicopathologic characteristics and overall and disease-free survival (DFS).


RESULTS
In a multivariate analysis, negative expression of CD44 and of SOX2 were both significant prognostic factors for DFS [hazard ratio (HR), 1.73; 95 % confidence interval (CI), 1.00-2.96; P = 0.046 and HR, 2.06; 95 % CI 1.14-3.70 P = 0.016). When CD44 and SOX2 expression were analyzed together, negative SOX2 expression was an independent prognostic factor for DFS (HR, 1.91; 95 % CI 1.05-3.46; P = 0.034). Low IRS scores for ALDH1 or Axin2 were associated with a reduced median survival (12.8 vs. 28.7 and 12.1 vs. 25.5 months, respectively). However, these markers and BMI1 were not prognostic factors for survival.


CONCLUSIONS
Loss of CD44 expression and loss of SOX2 expression are prognostic factors of poor survival in EAC patients. This suggests a role of these proteins in EAC that requires further investigation.
Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands, j.honing@umcg.nl.
Judith
J
Honing
Kirill V
KV
Pavlov
Coby
C
Meijer
Justin K
JK
Smit
Wytske
W
Boersma-van Ek
Arend
A
Karrenbeld
Johannes G M
JG
Burgerhof
Frank A E
FA
Kruyt
John Th M
JT
Plukker
D000230:Adenocarcinoma / Q000737:chemistry* / Q000601:surgery; D000368:Aged; D000080924:Aldehyde Dehydrogenase 1 Family; D060466:Axin Protein / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000737:chemistry* / Q000601:surgery; D016629:Esophagectomy; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis*; D007527:Isoenzymes / Q000032:analysis; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D063150:Polycomb Repressive Complex 1 / Q000032:analysis; D050697:Retinal Dehydrogenase / Q000032:analysis; D012189:Retrospective Studies; D055748:SOXB1 Transcription Factors / Q000032:analysis*; D015996:Survival Rate
C491761:AXIN2 protein, human; D060466:Axin Protein; C069077:BMI1 protein, human; D014408:Biomarkers, Tumor; D018960:Hyaluronan Receptors; D007527:Isoenzymes; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase; D063150:Polycomb Repressive Complex 1