title: A study to investigate the role of p27 and cyclin E immunoexpression as a prognostic factor in early breast carcinoma.
abstract: BACKGROUND
  Cyclin E and p27 expression is easy to assess in human tissues by standard immunohistochemical techniques. Immunohistochemistry is cost effective, relatively easy to perform and will play more of a role in the future management of cancer. The aim of this study was to investigate the role of p27 and cyclin E immunoexpression as a prognostic factor in early breast carcinoma.
  
  
  METHODS
  Cyclin E and p27 immunohistochemistry was performed on sixty six cases of breast carcinoma submitted over a five year period to the Division of Anatomical Pathology, Groote Schuur hospital; Whittaker and Associates; and PathCare. All tumours included in this study were less than 5 cm in diameter (pT1 and pT2 stage) and all the patients had wide local excisions performed. Follow up information was obtained from patient folders in the Department of Radiation Oncology.
  
  
  RESULTS
  There was no significant association of cyclin E and p27 expression with distant metastasis free survival (MFS) for all invasive carcinomas in contrast to grade, lymph node spread and vascular invasion. However, there was a statistically significant direct association of cyclin E with distant metastases in all invasive carcinomas, in the subgroup of infiltrating duct carcinomas (IDC) and in the node negative group when cyclin E was stratified as negative and positive (low/high). In this study of early breast carcinoma, only 9/66 cases showed cyclin E expression. Of these, four patients had distant metastases, one patient had a local recurrence and four patients were alive at last follow-up. Furthermore, cyclin E expression was significantly associated with grade, lymph node spread, oestrogen receptor status and histological type. None of the lobular carcinomas showed cyclin E positivity and only one case of lobular carcinoma presented with distant metastases.59/66 cases were positive (low/high) for p27 while seven cases were negative, 22 cases showed low expression and 37 cases demonstrated high p27 expression.p27 was significantly associated with oestrogen receptor status only for all invasive carcinomas and in the IDC group. There was no statistical relationship between p27 and cyclin E, but 50 (76%) tumours with positive p27 expression were negative for cyclin E. There were similar results for the invasive ductal carcinoma subgroup.
  
  
  CONCLUSIONS
  This study shows that p27 and cyclin E are not good independent prognostic markers for early breast carcinoma in contrast to grade, lymph node spread and vascular invasion for all invasive carcinomas. However, cyclin E provides some prognostic value as there is a direct statistical association with the development of distant metastases. Many previous studies have correlated overexpression of cyclin E with an aggressive course. The inverse relationship between p27 and cyclin E expression which has been reported in the literature has been highlighted, but this was not statistically significant. Most cases showed positive p27 expression and negative Cyclin E expression. This may be due to the early stage of the disease.
authors.affiliation: Department of Anatomical Pathology,NHLS, Red Cross Chidren's Hospital/Groote Schuur Hospital, University of Cape Town, South Africa. Komala.Pillay@uct.ac.za
authors.forename: Komala
authors.initials: K
authors.lastname: Pillay
authors.forename: Heather
authors.initials: H
authors.lastname: McCleod
authors.forename: Runjan
authors.initials: R
authors.lastname: Chetty
authors.forename: Pauline
authors.initials: P
authors.lastname: Hall
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D019927:Cyclin E / Q000032:analysis*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011379:Prognosis
chemical_list: D019927:Cyclin E; D050760:Cyclin-Dependent Kinase Inhibitor p27