title: Plasma DNA, microsatellite alterations, and p53 tumor mutations are associated with disease-free survival in radically resected non-small cell lung cancer patients: a study of the perugia multidisciplinary team for thoracic oncology.
abstract: BACKGROUND
  This prospective study examined association between circulating plasma DNA, microsatellite alterations (MA), p53 mutations with time to relapse and survival in surgically treated non-small cell lung cancer (NSCLC) patients (pts).
  
  
  METHODS
  Plasma samples, adjacent lung tissue, and lung tumor tissue specimens were collected from consecutive patients with stage I-III NSCLC. Blood samples of 66 matched healthy donors with positive smoking history were collected as controls. The plasma DNA amount was determined by real-time PCR. The analysis of MA at loci D3S1300, D3S1289, D3S1266, and D3S2338 on chromosome 3p was performed by radiolabeled PCR. p53 Mutations (exons 5, 6, 7, and 8) were detected by PCR-single-strand conformational polymorphism assay.
  
  
  RESULTS
  There were 76 patients, 65 men; median age was 68 years (range, 42-86), 20 had stage I, 40 stage II, and 16 stage III, the majority of pts (48.7%) had squamous-cell histology. Sixty-nine (91%) were smokers and most had good Eastern Cooperative Oncology Group performance status (0/1:72/4). Mean circulating DNA of all pts was 60 ng/ml versus 5 ng/ml in smoker-matched controls (p < 0.0001). In pts without recurrence, mean circulating DNA was 48.5 ng/ml at baseline, 32.8 ng/ml at 3 month, and 20.6 ng/ml at 12 month after surgery. In pts with recurrence, mean circulating DNA at baseline was 97.1 ng/ml. At 3 month after surgery, mean DNA concentration was significantly lower in disease-free pts than in patients with recurrent disease (32.8 versus 292.7 ng/ml; p = 0.0016). MA in at least one locus was found in 39.5% of NSCLC tumors. p53 Genomic mutations were observed in 54.0% of tumor samples. Statistically significant associations were observed between MA and squamous-cell histotype (p = 0.007) and between p53 mutations and lymph node involvement (p = 0.012). MA and p53 mutations were found to be significantly associated with recurrence of disease (p = 0.033 and 0.026, respectively).
  
  
  CONCLUSIONS
  Our results suggest that MA and p53 mutations in tumor DNA have a potential prognostic role for disease recurrence in NSCLC patients, and elevated levels of plasma circulating DNA identify patients with possible systemic disease at diagnosis. This might be proposed as an early detection test of disease recurrence.
authors: Medical Oncology Division, Azienda Ospedale Perugia, Via Brunamonti 51, 06122 Perugia, Italy. oncolab@hotmail.com
authors: Vienna
authors: V
authors: Ludovini
authors: Lorenza
authors: L
authors: Pistola
authors: Vanesa
authors: V
authors: Gregorc
authors: Irene
authors: I
authors: Floriani
authors: Eliana
authors: E
authors: Rulli
authors: Simonetta
authors: S
authors: Piattoni
authors: Luciana
authors: L
authors: Di Carlo
authors: Antonia
authors: A
authors: Semeraro
authors: Samir
authors: S
authors: Darwish
authors: Francesca Romana
authors: FR
authors: Tofanetti
authors: Lucia
authors: L
authors: Stocchi
authors: Zhasmina
authors: Z
authors: Mihaylova
authors: Guido
authors: G
authors: Bellezza
authors: Rachele
authors: R
authors: Del Sordo
authors: Giuliano
authors: G
authors: Daddi
authors: Lucio
authors: L
authors: Crinò
authors: Maurizio
authors: M
authors: Tonato
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000556:secondary / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000556:secondary / Q000601:surgery; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000556:secondary / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000556:secondary / Q000601:surgery; D016022:Case-Control Studies; D004247:DNA / Q000097:blood* / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008198:Lymph Nodes / Q000473:pathology / Q000601:surgery; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology / Q000601:surgery; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D004247:DNA