title: Cell proliferation index predicts relapse of brain metastases in non-irradiated patients.
abstract: BACKGROUND
  Brain metastasis is a common complication and a major cause of morbidity and mortality in human malignancies. We investigated whether the proliferating cell index of surgically treated single brain metastasis would predict the relapse at a location remote from the initial resection site within 2 months of the excision in patients with uncontrolled systemic disease and not subjected to adjuvant whole brain radio-therapy.
  
  
  METHODS
  Tissue biopsies derived from 25 patients with brain metastases specifically selected to be a single totally resected lesion and not treated subsequently by radiotherapy to the whole brain were stained by immunohistochemistry for the marker CDC47 and the proliferation index was calculated. The index was then analysed with respect to clinical parameters, including the incidence of brain relapse within 2 months of the first resection, the timing of diagnosis of brain metastasis as compared to the primary cancer diagnosis, and the perifocal brain oedema.
  
  
  RESULTS
  Statistical evaluation of the indexes in the patients with brain metastases relapsing within 2 months after the first craniotomy (n = 13) revealed significantly higher values as compared to the patients with lesions which had not relapsed or which had relapsed more than 2 months after first craniotomy (n = 12). The synchronous brain metastasis (that is, those occurring before or within 2 months of the primary cancer diagnosis) had a significantly higher proliferation index than the metachronous lesions (those occurring more than 2 months after primary cancer diagnosis).
  
  
  CONCLUSIONS
  The synchronous brain metastasis relapses within 2 months of primary resection and have a significantly higher proliferation index than the metachronous lesions which did not recur within 2 months. These results indicate that the estimation of the proliferation index of metastatic brain tumours may be helpful in predicting the course of disease progression.
authors.affiliation: Department of Neurosurgery, Otorhinolaringology and Ophthalmology, Medical University of Varna, Varna, Bulgaria. nikolay.a.peev@gmail.com
authors.forename: N A
authors.initials: NA
authors.lastname: Peev
authors.forename: A B
authors.initials: AB
authors.lastname: Tonchev
authors.forename: M
authors.initials: M
authors.lastname: Penkowa
authors.forename: S K
authors.initials: SK
authors.lastname: Kalevski
authors.forename: D G
authors.initials: DG
authors.lastname: Haritonov
authors.forename: G N
authors.initials: GN
authors.lastname: Chaldakov
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D001706:Biopsy; D001932:Brain Neoplasms / Q000556:secondary* / Q000601:surgery* / Q000628:therapy; D051928:CD47 Antigen / Q000032:analysis / Q000378:metabolism; D002277:Carcinoma / Q000556:secondary* / Q000601:surgery* / Q000628:therapy; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis*; D019635:Neurosurgical Procedures; D011237:Predictive Value of Tests
chemical_list: D014408:Biomarkers, Tumor; D051928:CD47 Antigen; C497894:CD47 protein, human