title: New aspects of the clinicopathology and genetic profile of metachronous multiple lung cancers.
abstract: OBJECTIVE
  For treatment decisions and prognostic applications, we evaluated p53/epidermal growth factor receptor (EGFR) somatic aberrations in metachronous multiple lung cancers to differentiate multiple primary lung cancers (MPLCs) from pulmonary metastases.
  
  
  BACKGROUND
  The current criteria to differentiate MPLCs from metastases are based on the histologic type and onset interval and do not incorporate genetic analysis. The genetic background of MPLCs remains unclear.
  
  
  METHODS
  Ninety-seven metachronous multiple lung cancers were identified to investigate somatic mutations in p53 and EGFR. Mutational analysis of p53 and EGFR was performed on DNA extracted from paraffin-embedded tumors.
  
  
  RESULTS
  A high frequency of somatic mutations in p53 (44.3%; 43/97) and/or EGFR (51.5%; 50/97) resulted in a high discrimination rate of tumor clonality (77.3%; 75/97) in metachronous multiple lung cancers. Of the 97 cases, 25 cases (33.3%) and 50 cases (66.7%) were assessed as having the same clonality (SC) and different clonality (DC), respectively. Notably, DC was commonly observed among tumors of the same histologic type (60.7%; 37/61), which further supported the carcinogenic theory of field cancerization. Multivariate analysis revealed that a first primary tumor of 3 cm or smaller (5-year survival: 92.7%; P = 0.001) and a limited resection of the latest tumor (5-year survival: 96.0%; P = 0.016) were 2 independent predictors of favorable prognosis.
  
  
  CONCLUSIONS
  Because most metachronous tumors of the same histologic type have different clonal origins, clonality assessment is essential to differentiate MPLCs from metastases. We recommend limited resection as the treatment of choice to achieve long-term survival in MPLCs patients with tumors of 3 cm or smaller.
authors.affiliation: Departments of *Pathology †Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan ‡Department of Surgery, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu City, Taiwan.
authors.forename: Chen-Tu
authors.initials: CT
authors.lastname: Wu
authors.forename: Mong-Wei
authors.initials: MW
authors.lastname: Lin
authors.forename: Min-Shu
authors.initials: MS
authors.lastname: Hsieh
authors.forename: Shuenn-Wen
authors.initials: SW
authors.lastname: Kuo
authors.forename: Yih-Leong
authors.initials: YL
authors.lastname: Chang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016609:Neoplasms, Second Primary / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D013624:Taiwan / Q000453:epidemiology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors