title: Correlation of decreased expression of PHLDA1 protein with malignant phenotype of gastric adenocarcinoma.
abstract: BACKGROUND
  Gastric carcinoma is one of the most aggressive malignancies with an extremely poor prognosis. Recent findings suggest decreasing PHLDA1 (pleckstrin-homologylike domain family A, member1) expression plays a significant role in inhibiting cell migration and tumor invasion. The clinicopathological significance of the expression of PHLDA1 in gastric carcinoma remains to be determined.
  
  
  METHODS
  PHLDA1 protein was investigated by immunohistochemistry for the expression status in 336 cases of gastric adenocarcinomas and 60 normal mucosa, and then the results were analyzed with the patient's age, sex, tumor site, size and the histological grade, clinical stage as well as overall median survival time.
  
  
  RESULTS
  The expression of PHLDA1 protein was obviously decreased in 57.1% of gastric carcinomas. Carcinomas with loss of expression of PHLDA1 were significantly corresponding to with tumor size (P=0.037), grade (P=0.028), depth of invasion (P=0.001), lymph node metastasis (P=0.008) and stage (P=0.001) but not with age (P=0.194), sex (P=0.312), tumor site (P=0.287) and distal metastasis (P=0.331) respectively. Follow-up data showed that there was a significant difference in overall median survival time between the carcinomas with PHLDA1 negative expression (31.0 months) and those with positive expression (54.0 months) (P=0.001).
  
  
  CONCLUSIONS
  Our findings suggest that the decreased expression of PHLDA1 may play an important role in tumor progression, and may become a new adjunct biomarker in the prognosis in gastric carcinoma. A potential role for PHLDA1 in the early detection/or therapy of gastric cancer warrants further investigation.
authors.affiliation: Department of Pathology, Chinese People's Liberation Army (PLA) General Hospital 28 Fuxing Road, Beijing 100853, China.
authors.forename: Po
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Chinese People's Liberation Army (PLA) General Hospital 28 Fuxing Road, Beijing 100853, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Pathology, Chinese People's Liberation Army (PLA) General Hospital 28 Fuxing Road, Beijing 100853, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D016022:Case-Control Studies; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010641:Phenotype; D016016:Proportional Hazards Models; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D013997:Time Factors; D014157:Transcription Factors / Q000032:analysis*; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; C491923:PHLDA1 protein, human; D014157:Transcription Factors
keywords: Gastric carcinoma; PHLDA1; immunohistochemistry; prognosis