[Relationship between tumor suppressor gene p16 and Rb and early diagnosis of lung cancers].
OBJECTIVE
To study the incidences and mechanisms of tumor suppressor gene p16 and Rb inactivation in lung cancers, and to investigate their relation to biological characters, clinical pathological diagnosis and gene classification diagnosis of lung cancers.


METHODS
Immunohistochemistry, double in situ hybridization, PCR, PCR-SSCP and sequencing were applied to study the changes of p16 and Rb genes in 106 lung cancers and 23 lung tissues of benign diseases.


RESULTS
Total expression rates of p16 and Rb proteins and mRNAs in lung cancers were lower than those in normal lung tissues and benign lung diseases, and they were specially related to histological type, metastasis and clinical stage of lung cancers. In stage I and II lung cancers, the obvious inactivation of tumor suppressor gene p16 or Rb was examined (32.6% or 28.3%); p16 inactivation was detected mainly in non-small cell lung cancers, and Rb inactivation mainly in small cell lung cancers. There were three mechanisms of homozygous deletions, methylations and mutations for p16 gene inactivation. The deletion rate of p16 exon1 and/or exon2 was 25.8%, mainly took place in p16 protein negative cases of non-small cell lung cancers. 15 cases (16.9%) took part in methylations on SmaI sites of CpG island of p16 gene. PCR-SSCP and sequencing showed that 9 cases had p16 gene mutations.


CONCLUSIONS
p16 and Rb genes may play important roles in genesis and progression of lung cancers. Inactivation of p16 or Rb gene may be is an early link of lung canceration, that is very important for early diagnosis of lung cancers. A new gene classification model for lung cancer diagnosis would be set up based on the research of p16 and Rb genes.
Ye
Y
Y
Cancer Center of People's Liberation Army, Nanjing 81st Hospital, Nanjing 210002, China.
Su
C
C
Wang
D
D
Liu
S
S
Liu
Y
Y
Liu
B
B
Cao
X
X
Shan
X
X
Wu
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D019175:DNA Methylation; D005260:Female; D017353:Gene Deletion; D020868:Gene Silencing; D016161:Genes, Retinoblastoma / Q000235:genetics*; D019942:Genes, p16; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D017354:Point Mutation