Loss of Heterozygosities in Barrett Esophagus, Dysplasia and Adenocarcinoma
B Zhu, SD Finkelstein, BJ Ujevich, JF Silverman, X Lin. Northwestern University, Chicago, IL; RedPath Integrated Pathology, Inc, Pittsburgh, PA; Allegheny General Hospital, Pittsburgh, PA
Background: Gastroesophageal biopsy (GEB) is widely utilized to evaluate gastroesophageal lesions that help guide surveillance for Barrett esophagus (BE) and low grade dysplasia (LGD) and treatment for high grade dysplasia (HGD) and adenocarcinoma. We evaluated whether there is a prograssive accumulation of genomic mutations from BE to malignant transformation and studied which genomic mutations are important in the transformation with GEB specimens.
Design: Representative cells of 34 GEBs including normal mucosa, BE, LGD, HGD and adenocarcinoma were microdissected and DNA from these cells were extracted. LOH was quantitatively determined for a broad panel of 17 microsatellite repeat markers targeting 10 tumor suppressor genes by PCR followed by automated capillary electrophoresis.
Table 1. Prograssive accumulation of LOHs in gastroesophageal lesionsStudent's T test. *: P < 0.05; **: P < 0.01.
|Group||LOHs (Mean SD)||LOHs Range||P Value|
|Normal Mucosa||0.00 0.00||0|
|BE||0.45 0.69||0 - 2||0.053|
|LGD||2.40 0.89||1 - 3||0.005**|
|HGD||4.75 1.50||4 - 7||0.043*|
|Adenocarcinoma||5.25 1.50||4 - 7||0.654|
Table 2. Frequency (%) of LOHs in gastroesophageal lesionsYates's correction test. *: P < 0.05; **: P < 0.01.
Conclusions: 1. There is a progressive accumulation of LOHs from BE to adenocarcinoma. 2. LOHs at 1p36 (CMM1 and MYCL1), 3p24 (VHL and PPAR), 9p21 (p16 and p14arf), and 17p13 (p53) may play an important role in BE, LOHs at 10q23 (pTEN), 17p13 and 17q12 (HER2/neu and NF1) in LGD, LOHs at 5q23 (APC and MCC) and 17q21 (NME1 and BRCA1) in HGD, and LOHs at 5q23 and 21q22 (TFF1 and PSEN2) in adenocarcinoma transformation. 3. Detection of LOHs targeting tumor suppressor genes can be useful in evaluating gastroesophageal lesions, studying oncogenesis of gastroesophageal adenocarcinoma, and determining surveillance for BE and LGD and/or treatment for HGD and adenocarcinoma.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 216, Tuesday Afternoon