title: Prognostic value of flow cytometric DNA analysis in non-small-cell lung cancer: rationale of sequential processing of frozen and paraffin-embedded tissue.
abstract: The objective of this study was to determine the prognostic information provided by flow cytometric DNA analysis in non-small-cell lung cancer. Lung samples of 132 consecutive patients submitted to surgery were prospectively processed. When no aneuploid populations were detected in fresh frozen samples, the process continued as a second step in paraffin-embedded tissue, consuming all the tumor available. The influence of ploidy on the postoperative outcome was studied by both a univariate and a multivariate analysis. Aneuploidy was found in 81 patients (61.4%). Fourteen patients showed no aneuploidy in fresh frozen samples; and only after further analysis in paraffin-embedded tissue was abnormal DNA detected. Overall, the 36-month survival was 69% for the diploid group and 24% for the aneuploid group (p = 0.0006). Including subjects submitted to complete tumor removal (stages I, II, and IIIA) in a multivariate analysis adjusted for TNM stage and histologic type, bearers of aneuploid tumors exhibited a higher risk of relapse (hazard ratio 2.65; CI 95% 1.5-4.66;p = 0.004) or death (hazard ratio 2.17; CI 95% 1.08-4.39;p = 0.032) than patients with diploid tumors. DNA ploidy resulted an independent prognostic factor of survival and tumor relapse in completely resected non-small-cell lung cancer. Sequential analysis of fresh and paraffin-embedded samples can help avoid the bias due to intratumoral DNA content heterogeneity. DNA ploidy could be an useful parameter in any future multifactorial analysis of outcome in such tumors.
authors.affiliation: Department of Surgery, Hospital Universitario San Carlos, Universidad Complutense, Madrid, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Mugüerza
authors.forename: M
authors.initials: M
authors.lastname: Díez
authors.forename: A J
authors.initials: AJ
authors.lastname: Torres
authors.forename: J A
authors.initials: JA
authors.lastname: López-Asenjo
authors.forename: A L
authors.initials: AL
authors.lastname: Picardo
authors.forename: A
authors.initials: A
authors.lastname: Gómez
authors.forename: F
authors.initials: F
authors.lastname: Hernando
authors.forename: R
authors.initials: R
authors.lastname: Cayón
authors.forename: J
authors.initials: J
authors.lastname: Granell
authors.forename: J L
authors.initials: JL
authors.lastname: Balibrea
mesh_terms: D000782:Aneuploidy; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D004273:DNA, Neoplasm / Q000032:analysis*; D004171:Diploidy; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016019:Survival Analysis; D015996:Survival Rate; D013997:Time Factors
chemical_list: D004273:DNA, Neoplasm