Aberrant expression of pRb, p16, p14ARF, MDM2, p21 and p53 in stage I adenocarcinomas of the lung.
Cancers are always associated with cell cycle abnormalities. To clarify the cell cycle abnormalities present in lung adenocarcinomas, various cell cycle regulatory proteins of both the pRb and p53 pathways were studied immunohistochemically in 50 cases of stage I adenocarcinoma of the lung. In regard to the pRb pathway, most adenocarcinomas showed frequent expression of both p16 and pRb proteins, and aberrant expression in the pRb pathway was observed in about one-quarter of stage I adenocarcinomas. In regard to the p53 pathway, the frequency of immunohistochemical positivity was 8% for p14ARF, 64% for MDM2, 20% for p53 and 24% for p21. In this pathway, the immunohistochemical profile of p14ARF-negative/MDM2-positive/p53-negative is characteristic of stage I adenocarcinoma of the lung. An inverse relationship was found between MDM2 and p53 protein and was associated with the differentiation status of stage I adenocarcinoma of the lung. Our results suggest that the disruption of the pRb and p53 pathways is frequently observed in the early stages of lung adenocarcinoma and might play an important role in the growth and differentiation of adenocarcinoma of the lung.
Xue
Qi
Q
Second Department of Pathology, Gunma University School of Medicine, Maebashi, Japan.
Sano
Takaaki
T
Kashiwabara
Kenji
K
Saito
Masako
M
Oyama
Tetsunari
T
Nakajima
Takashi
T
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D051736:Proto-Oncogene Proteins c-mdm2; D016160:Retinoblastoma Protein / Q000096:biosynthesis; D025803:Tumor Suppressor Protein p14ARF / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2