Frequent loss of heterozygosity of chromosome 1q in esophageal adenocarcinoma: loss of chromosome 1q21.3 is associated with shorter overall survival.
BACKGROUND
Previous microarray expression profiling studies have shown that genes located on chromosome region 1q21-23 were down-regulated in the progression of Barrett esophagus to esophageal adenocarcinoma and that, among patients with the latter condition, these genes were differentially expressed between responders and nonresponders of preoperative chemoradiation therapy. It was unclear whether this difference was due to loss of heterozygosity (LOH) or to other genetic alterations at this locus.


METHODS
The status of chromosome 1q LOH was retrospectively evaluated in formalin-fixed, paraffin-embedded pretreatment biopsy specimens from 33 patients with locally advanced esophageal adenocarcinoma who were treated with preoperative neoadjuvant therapy, and the findings were correlated with clinicopathologic features and overall survival duration. LOH was determined by polymerase chain reaction analysis of 7 dinucleotide microsatellite markers that spanned chromosomal region 1q21-23.


RESULTS
Allelic loss of chromosome 1q with any marker was found in 66% of tumors; 58% of tumors demonstrated loss of chromosome 1q21, and 45% of tumors demonstrated loss of chromosome 1q23. Patients with loss of chromosome 1q21.3 had shorter overall survival duration than patients without loss of chromosome 1q21.3 (P = .02). The difference in survival with loss of the chromosome 1q21.3 region was also found to be significant in a subset of patients with incomplete pathologic response to preoperative therapy (P = .024).


CONCLUSIONS
Loss of chromosome 1q was a frequent finding in esophageal adenocarcinoma cases, and loss of the 1q21.3 region was associated with shorter overall survival duration.
Maru
Dipen M
DM
Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. dmaru@mdanderson.org
Luthra
Rajyalakshmi
R
Correa
Arlene M
AM
White-Cross
Jill
J
Anandasabapathy
Sharmila
S
Krishnan
Sunil
S
Guha
Sushovan
S
Komaki
Ritsuko
R
Swisher
Stephen G
SG
Ajani
Jaffer A
JA
Hofstetter
Wayne L
WL
Rashid
Asif
A
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002878:Chromosomes, Human, Pair 1; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged