Expression of annexin A1 in esophageal and esophagogastric junction adenocarcinomas: association with poor outcome.
OBJECTIVE
Annexin A1 (ANXA1) is a calcium-binding protein involved in arachidonic acid metabolism and epidermal growth factor receptor tyrosine kinase pathway. ANXA1 has been implicated in early squamous cell carcinogenesis of esophagus and correlates with degree of tumor differentiation. However, the role of ANXA1 in esophageal adenocarcinoma is unclear. Our goal was to evaluate ANXA1 expression and determine its prognostic significance in adenocarcinoma of the esophagus and esophagogastric junction.


METHODS
This study included 104 consecutive patients with primary resected esophageal and esophagogastric junction adenocarcinomas (11 stage I, 24 stage II, 53 stage III, and 16 stage IV). ANXA1 protein expression in each tumor was assessed by immunohistochemical staining of tissue microarrays. ANAX1 expression level was classified as high (>/=25% of tumor cells with cytoplasmic staining), low (<25% of tumor cells with cytoplasmic staining), or negative; and was correlated with clinicopathologic features and patients' outcomes.


RESULTS
High ANXA1 expression was present in 39% (41 of 104) of tumors and was associated with higher pathologic T stage (P = 0.03) and distant metastasis (P = 0.04). High ANXA1 expression correlated with increased recurrence rate (P = 0.004) and decreased overall survival (P = 0.003) in univariate analysis. In multivariate analysis, ANXA1 expression and pN stage significantly correlated with recurrence rate (P = 0.008 and P < 0.001, respectively) and overall survival (P = 0.02 and P < 0.001, respectively) independent of T stage.


CONCLUSIONS
Our results indicate that high ANXA1 expression is frequent in esophageal and esophagogastric junction adenocarcinomas, correlates with more advanced pathologic T stage and the presence of distant metastasis, and is an independent prognostic factor for patient survival.
Wang
Kim L
KL
Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, 77030, USA.
Wu
Tsung-Teh
TT
Resetkova
Erika
E
Wang
Huamin
H
Correa
Arlene M
AM
Hofstetter
Wayne L
WL
Swisher
Stephen G
SG
Ajani
Jaffer A
JA
Rashid
Asif
A
Hamilton
Stanley R
SR
Albarracin
Constance T
CT
D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017305:Annexin A1 / Q000096:biosynthesis*; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy; D004943:Esophagogastric Junction / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis; D046888:Tissue Array Analysis; D016896:Treatment Outcome
D017305:Annexin A1