title: Prognostic value of HER2 status in bladder transitional cell carcinoma revealed by both IHC and BDISH techniques.
abstract: Her2/neu is an oncogene that plays an important role in the pathogenesis of many cancer types. In bladder carcinoma (BC), the clinical significance of Her2/neu status remains under-investigated and poorly linked to the patients' clinic-pathological features and survival status. Thus, the current study was conducted to assess Her2/neu status in a cohort of patients' in Saudi Arabia, and to explore its prognostic value in BC.
  
  
  
  A total of 160 consent patients of transitional cell carcinoma (TCC) of bladder were arranged on a tissue microarray (TMA) and stained by immunohistochemistry (IHC) and bright-field dual in situ hybridization (BDISH) methods. The intensity of Her2/neu protein receptor immunostaining was evaluated, correlated to Her2/neu gene amplification status in TCC and assessed for potential clinical value by correlation measures.
  
  
  
  IHC data demonstrated that Her2/neu protein is expressed in 60 % (2+ and 3+) of our TCC patient's cohort from Saudi Arabia. Her2/neu gene amplification is detected in 25 % by BDISH. There was a strong association between Her2/neu protein levels and lymph node invasion (p = 0.04), tumor stage (p = 0.002), vascular invasion and borderline significance with distant metastasis (p = 0.07). Amplification of Her2/neu gene was associated with tumor grade (p = 0.03) and poor disease-specific survival (p = 0.02), in that, patients with non-amplified Her2/neu gene live longer. Interestingly, there was a reasonable concordance rate (71 %) between IHC and BDISH data in the analyzed cohort.
  
  
  
  The study showed that 25 % of our patients' cohort has Her2/neu over-expression. This Her2/neu (over-expression/amplification) status was concordant using either IHC or BDISH and significantly associated with disease aggressiveness and poor outcome. These findings suggested a potential impact of anti-Her2 targeted therapy in the treatment of bladder cancer with amplified/overexpressed HER2 that needs further investigation.
authors.affiliation: King Fahd Medical Research Center, King Abdulaziz University, PO BOX 80216, Jeddah, 21589, Saudi Arabia.
authors.forename: Taoufik
authors.initials: T
authors.lastname: Nedjadi
authors.affiliation: Department of Pathology, Faculty of Medicine, King Abdulaziz University Hospital, Jeddah, Saudi Arabia.
authors.forename: Jaudah
authors.initials: J
authors.lastname: Al-Maghrabi
authors.affiliation: Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, King Abdulaziz University, PO BOX 80216, Jeddah, 21589, Saudi Arabia.
authors.forename: Mourad
authors.initials: M
authors.lastname: Assidi
authors.affiliation: Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, King Abdulaziz University, PO BOX 80216, Jeddah, 21589, Saudi Arabia.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Dallol
authors.affiliation: Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, King Abdulaziz University, PO BOX 80216, Jeddah, 21589, Saudi Arabia.
authors.forename: Heba
authors.initials: H
authors.lastname: Al-Kattabi
authors.affiliation: Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, King Abdulaziz University, PO BOX 80216, Jeddah, 21589, Saudi Arabia.
authors.forename: Adeel
authors.initials: A
authors.lastname: Chaudhary
authors.affiliation: Department of Urology, Faculty of Medicine, King Abdulaziz University Hospital, Jeddah, Saudi Arabia.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Al-Sayyad
authors.affiliation: Department of Urology, King Faisal Specialist Hospital & Research Centre, Jeddah, Saudi Arabia.
authors.forename: Adel
authors.initials: A
authors.lastname: Al-Ammari
authors.affiliation: Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, King Abdulaziz University, PO BOX 80216, Jeddah, 21589, Saudi Arabia.
authors.forename: Adel
authors.initials: A
authors.lastname: Abuzenadah
authors.affiliation: Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, King Abdulaziz University, PO BOX 80216, Jeddah, 21589, Saudi Arabia. abuhme@utu.fi.
authors.forename: Abdelbaset
authors.initials: A
authors.lastname: Buhmeida
authors.affiliation: Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, King Abdulaziz University, PO BOX 80216, Jeddah, 21589, Saudi Arabia.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Al-Qahtani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D017403:In Situ Hybridization / Q000379:methods*; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D016019:Survival Analysis; D046888:Tissue Array Analysis / Q000379:methods; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: BDISH; Her2/neu; IHC; Prognosis; Transitional cell carcinoma of bladder