title: The prognostic significance of proliferative indices in surgically resected IIIA-N2 non-small cell lung cancer after induction chemotherapy.
abstract: BACKGROUND
  The aim of this study was to assess the prognostic significance of Mib1 expression, Mitosis (Mi) and Apoptosis (Ai) in residual tumour cells after induction chemotherapy in surgically resected IIIA-N2 patients.
  
  
  METHODS
  Between January 2002 and November 2008, we reviewed 50 consecutive patients (39 males) with histologically proven stage IIIA-N2 non-small cell lung cancer (NSCLC), who underwent radical resection following induction chemotherapy. Five-year survival in the series was evaluated in relation to lymph node downstaging, histology, extent of resection, number of chemotherapy cycles, pT status, sex and age. It was then also evaluated in relation to the proliferative indexes (Mi, Ap and Mib 1 expression), dividing the patients into two groups according to whether they were above or below the 50th percentile for each parameter. The associations between mortality and the abovementioned prognostic factors were explored using the Kaplan-Meier method, the log-rank test, and Cox regression analysis.
  
  
  RESULTS
  The monovariate analysis confirmed the positive prognostic role of lymph node downstaging in terms of 5-yr survival: 31% vs. 12% (P=0.018). However Mi and Mib1 expression under the 50th percentile were also associated with better 5-yr survival: respectively 46% vs. 5% (P=0.007) and 40% vs. 6% (P=0.017). Neither apoptosis nor the other prognostic factors showed any statistical impact on long-term survival. The multivariate analysis showed Mi to be an independent prognostic factor (P=0.005).
  
  
  CONCLUSIONS
  Although lymph node downstaging has been considered the principal prognostic factor after induction chemotherapy and surgical resection, Mi and Mib1 expression in residual tumor can predict long-term survival more accurately.
authors.affiliation: Department of Thoracic Surgery, University Hospital of Siena, Siena, Italy - robcorzani@hotmail.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Corzani
authors.affiliation: Department of Thoracic Surgery, University Hospital of Siena, Siena, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Luzzi
authors.affiliation: Human Pathology, University Hospital of Siena, Siena, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Spina
authors.affiliation: Department of Thoracic Surgery, University Hospital of Siena, Siena, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Voltolini
authors.affiliation: Department of Thoracic Surgery, University Hospital of Siena, Siena, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Paladini
authors.affiliation: Department of Thoracic Surgery, University Hospital of Siena, Siena, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Ghiribelli
authors.affiliation: Department of Thoracic Surgery, University Hospital of Siena, Siena, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Ghisalberti
authors.affiliation: Department of Thoracic Surgery, University Hospital of Siena, Siena, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Borrelli
authors.affiliation: Department of Thoracic Surgery, University Hospital of Siena, Siena, Italy.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Meniconi
authors.affiliation: Department of Thoracic Surgery, University Hospital of Siena, Siena, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Monaci
authors.affiliation: Department of Thoracic Surgery, University Hospital of Siena, Siena, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gotti
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D049109:Cell Proliferation / Q000187:drug effects*; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy / Q000009:adverse effects / Q000401:mortality; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D008938:Mitosis / Q000187:drug effects; D008940:Mitotic Index; D020360:Neoadjuvant Therapy / Q000009:adverse effects / Q000401:mortality; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D011013:Pneumonectomy / Q000009:adverse effects / Q000401:mortality; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D019394:Ki-67 Antigen