title: Differing effects of adjuvant chemotherapy according to BRCA1 nuclear expression in gastric cancer.
abstract: BACKGROUND
  We aimed to investigate the role of BRCA1 nuclear expression in sporadic gastric cancer; currently, the role remains unknown.
  
  
  METHODS
  Patients with gastric cancer who received curative operation with D2 dissection were enrolled in this study. Adjuvant chemotherapy was administered at the discretion of the physician. According to BRCA1 nuclear expression analysis by immunohistochemistry (IHC) on tissue microarrays using anti-BRCA1 antibody MS110, BRCA1 expression was classified as negative, low expression, and high expression.
  
  
  RESULTS
  Among 318 cases, 155 cases (48.7 %) were identified as BRCA1-negative by IHC and 96 cases (30.2 %) revealed BRCA1 low expression, 67 cases (21.0 %) showed BRCA1 high expression. The negative or reduced expression of BRCA1 was more frequent in more advanced-stage disease (p < 0.001) and was associated with perineural invasion (p = 0.032). Disease-free survival (DFS) was significantly decreased with reduced BRCA1 expression (p = 0.027). This tendency was also observed in overall survival (OS), although the difference was not significant. The poorer prognosis of BRCA1-negative tumors was overcome through adjuvant chemotherapy. The benefit of adjuvant chemotherapy for DFS and OS in stage III was enhanced only in BRCA1-negative tumors (p < 0.001, p < 0.001, respectively), but not in BRCA1-positive tumors (p = 0.236, p = 0.148, respectively).
  
  
  CONCLUSIONS
  The reduction of BRCA1 nuclear expression is associated with advanced stage and perineural invasion. Moreover, negative BRCA1 nuclear expression is a predictive marker regarding the benefit of adjuvant chemotherapy in sporadic gastric cancer; these novel findings are of great importance, and further, larger studies are warranted.
authors: Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehang-ro, Jongno-gu, Seoul 110-744, Republic of Korea.
authors: Jin Won
authors: JW
authors: Kim
authors: Hyun Jin
authors: HJ
authors: Cho
authors: Miso
authors: M
authors: Kim
authors: Kyung-Hun
authors: KH
authors: Lee
authors: Min A
authors: MA
authors: Kim
authors: Sae-Won
authors: SW
authors: Han
authors: Do-Youn
authors: DY
authors: Oh
authors: Hyuk-Joon
authors: HJ
authors: Lee
authors: Seock-Ah
authors: SA
authors: Im
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: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002467:Cell Nucleus / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D012720:Severity of Illness Index; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D014408:Biomarkers, Tumor