title: Expression of prothymosin alpha predicts early recurrence and poor prognosis of hepatocellular carcinoma.
abstract: BACKGROUND
  Prothymosin alpha (PTMA) is a nuclear oncoprotein-transcription factor essential for cell cycle progression and proliferation. PTMA was overexpressed in several human malignancies including hepatocellular carcinoma (HCC). However, the prognostic significance of PTMA protein expression in HCC remains unclear. In the present study, we evaluated PTMA protein expression by immunohistochemistry in order to elucidate the prognostic roles of PTMA in HCC patients.
  
  
  METHODS
  By immunohistochemistry, we investigated the expression of PTMA protein in tumor tissue from 226 HCC patients who underwent curative hepatectomy. Univariate and multivariate analyses were performed to evaluate its predictive value for tumor recurrence and survival of patients. The median follow-up period was 120 months.
  
  
  RESULTS
  PTMA expression was observed in 162 (71.7%) of the 226 HCC patients and was significantly associated with higher Edmondson grade, microvascular invasion, intrahepatic metastasis, higher American Joint Committee on Cancer (AJCC) T-stage, and lower albumin level. PTMA expression was an independent predictor of early recurrence (P=0.001). PTMA expression showed an unfavorable influence on recurrence-free survival (RFS) (P<0.001). Subgroup analysis showed that among patients with tumor size ≤5.0 cm (140 patients), patients at AJCC T-stage 1 (95 patients) and patients with alpha-fetoprotein ≤20 ng/mL (83 patients), the differences in RFS between PTMA-positive and PTMA-negative groups were also statistically significant (P=0.017, P=0.002 and P=0.002, respectively). In addition, PTMA expression was an independent predictor of shorter RFS (P=0.011). PTMA expression showed an unfavorable influence on overall survival (P=0.014), but was not an independent predictor of shorter overall survival (P=0.161).
  
  
  CONCLUSIONS
  PTMA protein expression might be a novel predictor of early recurrence and RFS in HCC patients, even those at early stage or with alpha-fetoprotein-negative after curative hepatectomy. PTMA could be used as an immunohistochemical biomarker to detect patients with a high risk of recurrence.
authors: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. ckpark@skku.edu.
authors: Sang Yun
authors: SY
authors: Ha
authors: Dae Hyun
authors: DH
authors: Song
authors: Soo Hyun
authors: SH
authors: Hwang
authors: Soo Youn
authors: SY
authors: Cho
authors: Cheol-Keun
authors: CK
authors: Park
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000737:chemistry* / Q000556:secondary* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000737:chemistry* / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000737:chemistry*; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011498:Protein Precursors / Q000032:analysis*; D015996:Survival Rate; D013947:Thymosin / Q000031:analogs & derivatives* / Q000032:analysis; D047368:Tumor Burden; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D011498:Protein Precursors; D000509:alpha-Fetoproteins; C040782:prothymosin alpha; D013947:Thymosin