title: Evaluation of nuclear unrest and p53 immunostaining in Wilms' tumor.
abstract: BACKGROUND
  Nuclear unrest is a term applied to Wilms' tumors (WT) that show nuclear abnormalities close to anaplasia but without abnormal mitoses. p53 is claimed to be associated with anaplasia and poor prognosis. This study was undertaken to evaluate the clinical significance of nuclear unrest and p53 immunostaining in Wilms' tumor.
  
  
  METHODS
  This is a retrospective study of 63 patients who presented at NCI with Wilms' tumors, and underwent preoperative chemotherapy followed by nephrectomy. Histopathologic assessment and p53 immunohistochemistry were done.
  
  
  RESULTS
  WT with nuclear unrest grade III closely resembled anaplastic tumors and both of them (group 1) constituted 19% of cases. Group 1 constituted 29% of cases showing blastema dominant morphology compared to 9.4% of cases without blastema dominant morphology with significant statistical difference (p=0.047). Almost 83% of cases that achieved 1st complete remission were stages I, II and III, while 17% were stages IV and V with significant statistical difference (p<0.001). Stage affected the 3-year relapse-free-survival (RFS) significantly (p=0.014) as it was more in stages I, II and III than in stages IV and V (75.4% versus 50%). Blastema dominant morphology and high risk state significantly lowered the 3-year overall survival (OS) into 54.8% in comparison to 80.9% for cases with non-blastema dominant morphology (p=0.042). Regarding p53 immunohistochemistry, group 1 tumors showed positive p53 more than group 2 with significant statistical difference (p=0.014). p53 Positive immunostaining was significantly associated with high risk nephroblastoma (p=0.004).
  
  
  CONCLUSIONS
  Tumor stage and blastema dominant morphology are potent prognostic factors. p53 is linked to blastema dominant morphology. WT with nuclear unrest grade III closely resembles anaplastic WT. It may be appropriate to group tumors with nuclear unrest grade III with anaplastic histology regarding treatment stratification.
authors.affiliation: Department of Pathology, National Cancer Institute, Cairo University, Cairo, Egypt. almadina.salama@gmail.com
authors.forename: Asmaa
authors.initials: A
authors.lastname: Salama
authors.forename: Ahmad
authors.initials: A
authors.lastname: Kamel
mesh_terms: D000708:Anaplasia / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D009396:Wilms Tumor / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53