title: Ataxia-telangiectasia-mutated protein expression with microsatellite instability in gastric cancer as prognostic marker.
abstract: The prognostic significance of ataxia-telangiectasia-mutated (ATM) expression in gastric cancer remains unclear. The functional loss of ATM gene exhibits a biologic correlation with microsatellite instability (MSI). In this study, we investigated the significance of ATM expression with MSI by evaluating gastric cancer patients who had underwent curative resection. ATM expression was classified into low ATM expression (-, ±, +) and high ATM expression (++, +++) using immunohistochemistry analysis. MSI status was classified as MSI-negative (MSS, MSI-low) and MSI-positive (MSI-high). Of 321 patients, 205 (63.9%) exhibited low ATM expression and 116 (36.1%) exhibited high ATM expression. Low ATM expression was more frequently identified in patients of older age, more advanced stage and with MSI-positive tumor (p = 0.025, p = 0.001 and p = 0.014, respectively). The probability of 5-year disease-free survival (DFS) and overall survival (OS) was lower in low ATM expression group compared with the high ATM expression group (DFS: 62.5%, 76.4%, p = 0.017, OS: 65.9%, 78.5%, p = 0.027, respectively). According to MSI status, a subgroup of MSI-negative and low ATM expression cases exhibited the worst prognosis for DFS and OS; this subgroup also exhibited poorer DFS according to multivariable analysis (hazard radio = 1.8, 95% confidence interval, 1.2-2.8, p = 0.010), although prognostic value of ATM expression alone did not remain in the multivariable analysis. Taken together, these findings indicate that ATM expression with MSI status is an independent factor for gastric cancer prognosis in gastric cancer patients who received curative surgery.
authors: Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University, Seoul, Korea.
authors: Jin Won
authors: JW
authors: Kim
authors: Seock-Ah
authors: SA
authors: Im
authors: Min A
authors: MA
authors: Kim
authors: Hyun Jin
authors: HJ
authors: Cho
authors: Dae Won
authors: DW
authors: Lee
authors: Kyung-Hun
authors: KH
authors: Lee
authors: Tae-Yong
authors: TY
authors: Kim
authors: Sae-Won
authors: SW
authors: Han
authors: Do-Youn
authors: DY
authors: Oh
authors: Hyuk-Joon
authors: HJ
authors: Lee
authors: Tae-You
authors: TY
authors: Kim
authors: Han-Kwang
authors: HK
authors: Yang
authors: Woo Ho
authors: WH
authors: Kim
authors: Yung-Jue
authors: YJ
authors: Bang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064007:Ataxia Telangiectasia Mutated Proteins / Q000096:biosynthesis* / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality
chemical_list: D014408:Biomarkers, Tumor; D064007:Ataxia Telangiectasia Mutated Proteins
keywords: adjuvant; ataxia-telangiectasia-mutated; gastric cancer; microsatellite instability; prognosis