Stepwise radical endoscopic resection of the complete Barrett's esophagus with early neoplasia successfully eradicates pre-existing genetic abnormalities.
OBJECTIVE
Malignant transformation of Barrett's mucosa is associated with the accumulation of genetic alterations. Stepwise radical endoscopic resection of the Barrett's segment with early neoplasia is a promising new treatment resulting in complete re-epithelialization of the esophagus with neosquamous epithelium. It is unknown whether radical resection also eradicates genetic abnormalities. The aim of this study was to prospectively evaluate whether genetic abnormalities as found in the Barrett's segment before radical resection are effectively eradicated and absent in the neosquamous epithelium.


METHODS
Nine patients with early neoplasia who successfully underwent radical resection were included. Immunohistochemistry (IHC) was performed to assess p53 protein overexpression. DNA fluorescent in-situ hybridization was (DNA-FISH) performed for evaluation of numerical abnormalities of chromosomes 1 and 9, and losses of p16 and p53. Immunohistochemistry and DNA-FISH were performed on endoscopic resection specimens of the neoplasia and on follow-up biopsies of the neosquamous epithelium.


RESULTS
DNA-FISH and IHC showed alterations in the pretreatment samples of all patients. All showed aneusomy of chromosome 1 and 9. Loss of p16 and p53 were seen in 6 and 8 patients. IHC showed intense p53 nuclear staining in seven patients. Post-treatment biopsies showed neosquamous epithelium with a normal diploid signal count for all DNA-FISH probes and normal IHC stainings in all patients.


CONCLUSIONS
Radical resection of Barrett's esophagus with early neoplasia successfully eradicates pre-existing genetic abnormalities and results in neosquamous epithelium without these genetic abnormalities.
Peters
Femke P
FP
Laboratory of Experimental Internal Medicine, Amsterdam, The Netherlands.
Krishnadath
K K
KK
Rygiel
Agnieszka M
AM
Curvers
Wouter L
WL
Rosmolen
Wilda D
WD
Fockens
P
P
Ten Kate
Fiebo J W
FJ
van Baal
Jantine W P M
JW
Bergman
Jacques J G H M
JJ
D000230:Adenocarcinoma / Q000235:genetics / Q000601:surgery*; D001471:Barrett Esophagus / Q000235:genetics* / Q000601:surgery*; D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000601:surgery*; D004945:Esophagoscopy; D019942:Genes, p16; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D011230:Precancerous Conditions / Q000235:genetics / Q000601:surgery; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D016159:Tumor Suppressor Protein p53