Aberrant cytological localization of p16 and CDK4 in colorectal epithelia in the normal adenoma carcinoma sequence.
OBJECTIVE
To study the correlation between the patterns of subcellular expression of p16 and CDK4 in colorectal epithelia in the normal-adenoma-carcinoma sequence.


METHODS
Paraffin sections of 43 cases of normal colorectal epithelia and corresponding adenomas as well as carcinomas were analysed immunocytochemically for subcellular expression of p16 and CDK4 proteins.


RESULTS
Most carcinomas showed more cytoplasmic overexpression for p16 and CDK4 than the adenomas from which they arised or the adjacent normal mucosa. Most normal or non-neoplastic epithelia showed more p16 and CDK4 expression in the nucleus than their adjacent adenomas and carcinomas. There was a significant difference between the subcellular expression pattern of p16 and CDK4 in normal-adenoma-carcinoma sequence epithelia (P < 0.001). Neither p16 nor CDK4 subcellular patterns correlated with histological grade or Dukes' stage.


CONCLUSIONS
Interaction of expression of p16 and CDK4 plays an important role in the Rb/p16 pathway. Overexpression of p16 and CDK4 in the cytoplasm, as well as loss expression of p16 in the nucleus might be important in the evolution of colorectal carcinoma from adenoma and, of adenoma from normal epithelia.
Zhao
Po
P
Department of Pathology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China. zhaopo@plagh.com.cn
Mao
Xin
X
Talbot
Ian C
IC
D000236:Adenoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D012189:Retrospective Studies
D019941:Cyclin-Dependent Kinase Inhibitor p16; D051358:Cyclin-Dependent Kinase 4