2004 Summer Meeting - Amsterdam - The Pathological Society of ...

129
DNA Double Strand Break Repair And Mismatch Repair in
Gastric Cancer – Are ATM And BRCA The Connection?
M Dattani 1 , K Maude 2 , L Barker 3 , S Gray 3 , H Sue-Ling 2 , M
Dixon 3 , P Quirke 1 , H Grabsch 1
1 Academic Unit of Pathology, University of Leeds, Leeds, United
Kingdom, 2 Academic Unit of Surgery, Leeds Teaching Hospitals NHS
Trust, Leeds, United Kingdom, 3 Dept of Histopathology, Leeds Teaching
Hospitals NHS Trust, Leeds, United Kingdom
Impaired DNA repair may contribute to genomic instability and malignant
transformation. It has been suggested that a BRCA1-associated protein complex
coordinates both, DNA double-strand break [DSB] repair and mismatch repair
[MMR]. However, the expression of BRCA1 and other proteins involved in
DSB repair, and their relationship to MMR protein expression has not been
investigated in sporadic gastric cancer [GC].
We investigated the expression of DSB repair proteins (ATM, BRCA1,
BRCA2) and MMR proteins (MSH2 and MLH1) by immunohistochemistry on
tissue microarrays constructed from 163 GC. The percentage of positive tumour
cells was assessed and correlated with clinicopathological data and patient
survival.
ATM and BRCA1 expression was reduced in all GC compared to normal
mucosa, whereas BRCA2 expression was increased. Furthermore, ATM and
BRCA1 expression was significantly lower in intestinal-type GC compared to
diffuse-type GC. MSH2 expression was lost in 6 GC, MLH1 expression was
lost in 11 GC. Loss of MMR protein expression was significantly associated
with reduced or loss of expression of ATM, BRCA1 and BRCA2. Low BRCA2
expression (