BACKGROUND: Synchronous multiple primary lung tumors (SMPLT) have been estimated to occur in 1% of lung carcinoma patients. Criteria for SMPLT diagnosis include different cancer histologies, location in different lobes of the lung, or genetic discordance. Patients with SMPLT have a poor clinical prognosis with decreased 5-year disease survival, despite diagnosis at an early stage. Field cancerization (the induction of somatic mutation in large clones of epithelial cells after carcinogen exposure) has been proposed to be an integral process involved in the development of SMPLT. Host factors also may contribute to the development of SMPLT. METHODS: The authors investigated the occurrence of p53 and K-ras alterations in tumors from SMPLT patients and also studied the association between carcinogen exposure and polymorphic metabolic traits in SMPLT patients, comparing these patients with individuals with one primarily lung tumor. RESULTS: In a case-control study of lung carcinoma susceptibility, 6 patients were identified whose 33 multiple tumors met the criteria of SMPLT. The incidence was 3.6% (16 of 451 patients), which was higher than many previously published series. Among the multiple tumors, 73% (24 of 33 tumors) were adenocarcinomas. Patients with SMPLT smoked more (73.0 pack-years vs. 56.2 pack-years; P = 0.07) and longer (45.8 years vs. 37.0 years; P < 0.03) than patients with only 1 tumor. For those patients who stopped smoking, patients with SMPLT had stopped smoking more recently than those with a single primary tumor (3.4 years vs. 7.3 years; P = 0.08). A total of 39% of SMPLT tumors (13 of 33 tumors) had detectable p53 alterations; 36% had genetic changes in p53 measured by polymerase chain reaction-single strand conformation polymorphism, and 33% showed positive immunostaining for p53 protein. This was comparable to the occurrence of p53 mutations and immunostaining in single tumor cases (30%). Age, gender, family history of cancer, and the prevalence of polymorphic metabolic traits previously associated with lung carcinoma susceptibility did not differ among SMPLT patients compared with patients with a single tumor. CONCLUSIONS: The patients with SMPLT had significantly more tobacco exposure, and their tumors apparently had independently arising p53 and K-ras mutations, suggesting that field cancerization may be important in lung carcinogenesis.
BACKGROUND: Synchronous multiple primary lung tumors (SMPLT) have been estimated to occur in 1% of lung carcinomapatients. Criteria for SMPLT diagnosis include different cancer histologies, location in different lobes of the lung, or genetic discordance. Patients with SMPLT have a poor clinical prognosis with decreased 5-year disease survival, despite diagnosis at an early stage. Field cancerization (the induction of somatic mutation in large clones of epithelial cells after carcinogen exposure) has been proposed to be an integral process involved in the development of SMPLT. Host factors also may contribute to the development of SMPLT. METHODS: The authors investigated the occurrence of p53 and K-ras alterations in tumors from SMPLT patients and also studied the association between carcinogen exposure and polymorphic metabolic traits in SMPLT patients, comparing these patients with individuals with one primarily lung tumor. RESULTS: In a case-control study of lung carcinoma susceptibility, 6 patients were identified whose 33 multiple tumors met the criteria of SMPLT. The incidence was 3.6% (16 of 451 patients), which was higher than many previously published series. Among the multiple tumors, 73% (24 of 33 tumors) were adenocarcinomas. Patients with SMPLT smoked more (73.0 pack-years vs. 56.2 pack-years; P = 0.07) and longer (45.8 years vs. 37.0 years; P < 0.03) than patients with only 1 tumor. For those patients who stopped smoking, patients with SMPLT had stopped smoking more recently than those with a single primary tumor (3.4 years vs. 7.3 years; P = 0.08). A total of 39% of SMPLT tumors (13 of 33 tumors) had detectable p53 alterations; 36% had genetic changes in p53 measured by polymerase chain reaction-single strand conformation polymorphism, and 33% showed positive immunostaining for p53 protein. This was comparable to the occurrence of p53 mutations and immunostaining in single tumor cases (30%). Age, gender, family history of cancer, and the prevalence of polymorphic metabolic traits previously associated with lung carcinoma susceptibility did not differ among SMPLT patients compared with patients with a single tumor. CONCLUSIONS: The patients with SMPLT had significantly more tobacco exposure, and their tumors apparently had independently arising p53 and K-ras mutations, suggesting that field cancerization may be important in lung carcinogenesis.
Authors: William D Travis; Elisabeth Brambilla; Masayuki Noguchi; Andrew G Nicholson; Kim R Geisinger; Yasushi Yatabe; David G Beer; Charles A Powell; Gregory J Riely; Paul E Van Schil; Kavita Garg; John H M Austin; Hisao Asamura; Valerie W Rusch; Fred R Hirsch; Giorgio Scagliotti; Tetsuya Mitsudomi; Rudolf M Huber; Yuichi Ishikawa; James Jett; Montserrat Sanchez-Cespedes; Jean-Paul Sculier; Takashi Takahashi; Masahiro Tsuboi; Johan Vansteenkiste; Ignacio Wistuba; Pan-Chyr Yang; Denise Aberle; Christian Brambilla; Douglas Flieder; Wilbur Franklin; Adi Gazdar; Michael Gould; Philip Hasleton; Douglas Henderson; Bruce Johnson; David Johnson; Keith Kerr; Keiko Kuriyama; Jin Soo Lee; Vincent A Miller; Iver Petersen; Victor Roggli; Rafael Rosell; Nagahiro Saijo; Erik Thunnissen; Ming Tsao; David Yankelewitz Journal: J Thorac Oncol Date: 2011-02 Impact factor: 15.609
Authors: Cheng Shen; Xin Wang; Long Tian; Yubin Zhou; Dali Chen; Heng Du; Weiya Wang; Lunxu Liu; Guowei Che Journal: Eur J Med Res Date: 2015-02-20 Impact factor: 2.175