title: Rt-PCR increases detection of submicroscopic peritoneal metastases in gastric cancer and has prognostic significance.
abstract: BACKGROUND
  Positive peritoneal cytology confers the same prognosis as clinical stage IV disease in gastric cancer. Conventional cytology examination, however, has low sensitivity. We hypothesize that real-time polymerase chain reaction (RT-PCR) may have increased sensitivity and provide more accurate staging information.
  
  
  METHODS
  From February 2007 to April 2009, peritoneal lavage samples were collected prospectively from 156 patients with biopsy-proven gastric cancer undergoing staging laparoscopy. These washings were analyzed by both Papanicolaou staining and RT-PCR for the tumor marker carcinoembryonic antigen (CEA).
  
  
  RESULTS
  Visible peritoneal disease was seen at laparoscopy in 38 patients (LAP+, 24%). Cytology was positive (CYT+) in 23 patients, while RT-PCR was positive (PCR+) in 30. The sensitivity of CYT for the detection of visible disease was 61% compared to 79% for PCR (P = 0.02). No visible peritoneal disease was seen at laparoscopy (LAP-) in 118 (76%) patients. Eight (7%) were CYT+, while 28 (24%) were PCR+. Predictors of PCR positivity included advanced-stage disease (T3-4 vs. T1-2 tumors) and poor pathologic features such as vascular or perineural invasion. Long-term follow-up demonstrated a worse survival of LAP-CYT-PCR+ (P = 0.0003) and LAP-CYT+PCR+ (P = 0.0004) compared to LAP-CYT-PCR- patients. There was no significant difference in survival between CYT-PCR+ and CYT+PCR+ patients. PCR positivity also predicted a higher likelihood of disease recurrence after resection. An R0 resection was performed in 85 LAP- patients (54%): only 1 (1%) was CYT+, while 13 (15%) were PCR+. Of this group, PCR+ demonstrated a worse survival than PCR- patients (P = 0.02). Further analysis showed that, in R0 resection, stage III/IV, CYT- subgroup, PCR+ was associated with a trend towards worse survival (P = 0.09) compared to PCR- patients.
  
  
  CONCLUSIONS
  RT-PCR for CEA increases the detection of subclinical peritoneal disease and is more sensitive than cytology. Predictors of positive PCR included advanced-stage disease, vascular invasion, and perineural invasion. PCR positivity was associated with increased disease recurrence and decreased survival. Further follow-up is required to determine if PCR positivity alone is an independent predictor of poor survival in gastric cancer.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, 275 York Avenue, New York, NY 10021, USA.
authors.forename: Joyce
authors.initials: J
authors.lastname: Wong
authors.forename: Kaitlyn Jane
authors.initials: KJ
authors.lastname: Kelly
authors.forename: Arjun
authors.initials: A
authors.lastname: Mittra
authors.forename: Mithat
authors.initials: M
authors.lastname: Gonen
authors.forename: Peter
authors.initials: P
authors.lastname: Allen
authors.forename: Yuman
authors.initials: Y
authors.lastname: Fong
authors.forename: Daniel
authors.initials: D
authors.lastname: Coit
mesh_terms: D000328:Adult; D001707:Biopsy, Needle; D016009:Chi-Square Distribution; D015331:Cohort Studies; D003581:Cytodiagnosis / Q000379:methods; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D010535:Laparoscopy / Q000379:methods; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods*; D010533:Peritoneal Lavage; D010534:Peritoneal Neoplasms / Q000401:mortality / Q000473:pathology / Q000556:secondary* / Q000601:surgery*; D016133:Polymerase Chain Reaction / Q000379:methods; D011237:Predictive Value of Tests; D011300:Preoperative Care / Q000379:methods; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods*; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D013274:Stomach Neoplasms / Q000401:mortality / Q000473:pathology / Q000556:secondary* / Q000601:surgery*; D016019:Survival Analysis
chemical_list: D012333:RNA, Messenger