Distinct patterns of p27/KIP 1 gene expression in hepatoblastoma and prognostic implications with correlation before and after chemotherapy.
Over the past 3 years, numerous studies have examined the diagnostic and prognostic significance of p27/Kip1 expression in various tumors. Almost all studies report decreased p27 expression in more aggressive tumors. Information about morphologic changes due to chemotherapy in hepatoblastoma (Hbs) is limited, and so is information about distinct patterns of p27 gene expression. Twenty-nine hepatoblastomas were evaluated for possible prognostic correlation between p27 expression in different histotypes of hepatoblastoma, changes during chemotherapy, and outcome. These observations should prompt prospective randomized studies designed to investigate the predictive role of p27 expression in different Hbs histotypes. Patients were treated according to the Children's Cancer Group and Pediatric Oncology Group protocols, which included initial surgery before chemotherapy wherever possible. Follow-up ranged from 1 to 133 months. The results show that primary well-differentiated fetal tumors without mitotic activity are strongly p27 positive. The embryonal pattern displays a variable p27 protein expression pattern, with focal positivity between completely negative zones; p27 is positive where the mitotic activity is low or absent and negative where the mitogenic activity is high. The vast majority of small undifferentiated cell components are p27 negative. p27 protein expression is downregulated after chemotherapy in the remaining fetal well-differentiated component of Hbs. Although this may imply selection of a more aggressive clone, all patients with this histology were cured in this series. Aggressiveness and ultimate prognosis for incompletely resected tumors after chemotherapy remain indeterminate.
Brotto
Maurizio
M
Department of Pathology, Texas Children's Hospital, Houston, TX 77030, USA.
Finegold
Milton J
MJ
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018797:Cell Cycle Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017809:Fatal Outcome; D005260:Female; D015870:Gene Expression; D018197:Hepatoblastoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D018797:Cell Cycle Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27