Correlation of histology with biomarker status after photodynamic therapy in Barrett esophagus.
BACKGROUND
Currently, histology is used as the endpoint to define success with photodynamic therapy (PDT) in patients with high-grade dysplasia (HGD). Recurrences despite 'successful' ablation are common. The role of biomarkers in assessing response to PDT remains undefined. The objectives of the current study were 1) to assess biomarkers in a prospective cohort of patients with HGD/mucosal cancer before and after PDT and 2) to correlate biomarker status after PDT with histology.


METHODS
Patients who underwent PDT for HGD/mucosal cancer were studied prospectively. All patients underwent esophagogastroduodenoscopy, 4-quadrant biopsies every centimeter, endoscopic mucosal resection of visible nodules, and endoscopic ultrasound. Cytology samples were obtained by using standard cytology brushes. Biomarkers were assessed by using fluorescence in situ hybridization (FISH). The biomarkers that were assessed included loss of 9p21 (site of the p16 gene) and 17p13.1 (site of the p53 gene) loci; gains of the 8q24(c-myc), 17q (HER2-neu), and 20q13 loci; and multiple gains. Patients received PDT 48 hours after the administration of sodium porfimer. Demographic and clinical variables were collected prospectively. Patients were followed with endoscopy and repeat cytology for biomarkers. The McNemar test was used to compare biomarker proportions before and after PDT.


RESULTS
Thirty-one patients were studied. The median patient age was 66 years (interquartile range [IQR], 56-73 years), and 28 patients (88%) were men. The mean Barrett segment length was 5 cm (standard error of the mean, 0.5 cm). Post-PDT biomarkers were obtained after a median duration of 9 months (IQR, 3-12 months). There was a statistically significant decrease in the proportion of several biomarkers assessed after PDT. Six patients without HGD after PDT still had positive FISH results for 1 or more biomarkers: of these, 2 patients (33%) developed recurrent HGD.


CONCLUSIONS
In this initial study, histologic downgrading of dysplasia after PDT was associated with the loss of biomarkers that have been associated with progression of neoplasia in Barrett esophagus. Patients with persistently positive biomarkers appeared to be at a higher risk of recurrent HGD. These findings should be confirmed in a larger study.
Barrett Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Ganapathy A
GA
Prasad
Kenneth K
KK
Wang
Kevin C
KC
Halling
Navtej S
NS
Buttar
Louis-Michel
LM
Wongkeesong
Alan R
AR
Zinsmeister
Shannon M
SM
Brankley
Wytske M
WM
Westra
Lori S
LS
Lutzke
Lynn S
LS
Borkenhagen
Kelly
K
Dunagan
D000368:Aged; D000465:Algorithms; D001471:Barrett Esophagus / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D015415:Biomarkers / Q000032:analysis*; D002277:Carcinoma / Q000188:drug therapy / Q000473:pathology; D017323:Dihematoporphyrin Ether / Q000627:therapeutic use*; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D010778:Photochemotherapy; D012008:Recurrence
D015415:Biomarkers; D017323:Dihematoporphyrin Ether