title: Patterns of disease recurrence influenced by hematogenous tumor cell dissemination in patients with cervical carcinoma of the uterus.
abstract: BACKGROUND
  The presence of isolated tumor cells (ITC) in the bone marrow at the time of primary diagnosis indicates an increased risk for subsequent development of distant metastases in various solid tumors. This study evaluates the prevalence and prognostic significance of ITC in patients with primary carcinoma of the cervix uteri.
  
  
  METHODS
  We immunocytochemically analyzed bone marrow aspirates of 130 patients with newly diagnosed carcinoma of the cervix uteri for the presence of cytokeratin(CK)-positive cells from May 1994 to January 2001. We used a quantitative immunoassay with the monoclonal anti-CK antibody A45-B/B3 and evaluated 2 x 10(6) bone marrow cells per patient. Patients were followed prospectively for a median of 43 (range, 1-85) months.
  
  
  RESULTS
  Isolated tumor cells were found in the bone marrow of 38 patients (29%). The presence of ITC did not correlate with the International Federation of Gynecology and Obstetrics (FIGO) tumor stage (P = 0.61), pelvic and paraaortal lymph node involvement (P = 0.41), histopathologic grading (P = 0.67), the histologic type of the carcinoma (P = 0.93), invasion of lymph nodes (P = 0.93) and blood vessels (P = 0.92), or with menopausal status (P = 0.17). The bone marrow status at the time of primary diagnosis did not correlate with the overall survival as estimated by Kaplan-Meier analysis (P = 0.30). However, distant metastases occurred in 5% of the patients (n = 5) with negative bone marrow status and in 15% of the patients (n = 6) with positive bone marrow status (P = 0.054). The median distant disease-free survival period was 78 months (95% confidence interval 73-82) in patients with negative bone marrow status and 72 months (95% CI 61-82) in patients with positive bone marrow status (P = 0.051). Multivariate analysis revealed the presence of ITC as a significant, independent risk factor for the subsequent development of distant metastases (relative risk 3.6, P = 0.046).
  
  
  CONCLUSIONS
  Despite the locoregional predominance of cervical carcinoma at the time of primary diagnosis, the presence of ITC in the bone marrow indicates an increased risk for the development of distant metastases. This information may prove useful to stratify patients for systemic treatment.
authors.affiliation: Department of Gynecology and Obstetrics, I Frauenklinik, Klinikum der Ludwig-Maximilians-Universtitaet, Muenchen, Germany. janni@fk-i.med.uni-muenchen.de
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Janni
authors.forename: Florian
authors.initials: F
authors.lastname: Hepp
authors.forename: Barbara
authors.initials: B
authors.lastname: Strobl
authors.forename: Brigitte
authors.initials: B
authors.lastname: Rack
authors.forename: Dorothea
authors.initials: D
authors.lastname: Rjosk
authors.forename: Christina
authors.initials: C
authors.lastname: Kentenich
authors.forename: Christian
authors.initials: C
authors.lastname: Schindlbeck
authors.forename: Peer
authors.initials: P
authors.lastname: Hantschmann
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
authors.forename: Harald
authors.initials: H
authors.lastname: Sommer
authors.forename: Stephan
authors.initials: S
authors.lastname: Braun
mesh_terms: D000328:Adult; D019046:Bone Marrow Neoplasms / Q000378:metabolism / Q000556:secondary*; D002277:Carcinoma / Q000378:metabolism / Q000556:secondary*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007633:Keratins / Q000378:metabolism; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D016019:Survival Analysis; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy
chemical_list: D007633:Keratins