title: IMP3 can predict aggressive behaviour of lung adenocarcinoma.
abstract: BACKGROUND
  Lung cancer most often presents as an inoperable tumour and the diagnosis is usually performed on a small biopsy/cytology specimen. In the group of non small cell lung cancer - not otherwise specified, adenocarcinoma phenotype can be determined immunohistochemically using TTF-1 and Napsin A. Expression of oncofetal protein IMP3 in human cancer is associated with poor differentiation and aggressive behaviour. In the present study expression of IMP3 was correlated with expression of TTF-1 and Napsin A, histological subtype and clinical stage of lung adenocarcinoma. We were interested whether distant metastases are associated with IMP3 overexpression, regardless of the histologic subtype of adenocarcinoma.
  
  
  METHODS
  In retrospective study, consecutive series of 105 patients with advanced lung adenocarcinoma diagnosed from 2006 to 2009 in Clinical Hospital Center Split, Croatia, were analysed. Clinical data were collected from the Pulmology Department and time of death from the Mortality Registry. Paraffin blocks of bronchoscopic biopsies were collected from the Institute of Pathology and 15 cases excluded from the analysis due to insufficient material. Expression of IMP3, Napsin A and TTF-1 were analysed by indirect enzyme immunohistochemistry. Statistical analysis was performed and P values less than 0.05 considered significant.
  
  
  RESULTS
  Of 90 patients, 71 (78%) were males and 19 (22%) females. Median age for males was 61.5 years (min-max 43-83) and for females 61 years (min-max 44-86). Pleural effusion was found in 15 (16.6%) and distant metastases in 45 (50%) cases. According to histological subtypes, there were 34 acinar, 2 lepidic, 2 papillary and 52 solid subtypes. IMP3 overexpression was found in 63 cases (70%) and was correlated with solid subtype (P = 0.002) and negative/weak Napsin A expression (P = 0.004). Strong Napsin A expression correlated with TTF-1 expression (P = 0.003) and lower histological grades (P = 0.031). Patients with IMP3 overexpression more often had distant metastases than patients with negative IMP3, 55.5% versus 33.3% (P = 0.033). Non solid subtypes with IMP3 overexpression developed distant metastasis more common than non solid subtypes with negative IMP3, 72% versus 35% (P = 0.028).
  
  
  CONCLUSIONS
  Expression of IMP3 correlates with solid subtype and with distant metastases regardless of histological subtype of lung adenocarcinoma.
  http://www.diagnosticpathology.diagnomx.eu/vs/1966211581795258
authors.affiliation: Institute for pathology, forensic medicine and cytology Clinical Hospital Center Split, Split, Croatia.
authors.forename: Renata
authors.initials: R
authors.lastname: Beljan Perak
authors.forename: Merica Glavina
authors.initials: MG
authors.lastname: Durdov
authors.forename: Vesna
authors.initials: V
authors.lastname: Capkun
authors.forename: Veljka
authors.initials: V
authors.lastname: Ivcevic
authors.forename: Antonia
authors.initials: A
authors.lastname: Pavlovic
authors.forename: Violeta
authors.initials: V
authors.lastname: Soljic
authors.forename: Mari
authors.initials: M
authors.lastname: Peric
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016282:Aspartic Acid Endopeptidases / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D001999:Bronchoscopy; D016009:Chi-Square Distribution; D017523:Croatia; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000032:analysis; D016612:Paraffin Embedding; D011237:Predictive Value of Tests; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000032:analysis*; D012189:Retrospective Studies; D016019:Survival Analysis; D000074482:Thyroid Nuclear Factor 1; D013997:Time Factors; D014157:Transcription Factors / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; C498780:IGF2BP3 protein, human; C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D016282:Aspartic Acid Endopeptidases; C498549:NAPSA protein, human