p22/WAF1 expression in human colorectal carcinoma: association with p53, transcription factor AP-2 and prognosis.
p21/WAF1 expression was studied in a series of 162 colorectal carcinoma patients and its relation to p53- and activator protein (AP)-2 expressions and to stage as well as survival was assessed. p21 expression was moderate or intense in 33% of the tumours, and 53% of the tumours had moderate or strong p53 staining intensity. Eighty-nine percent of the tumours showed a weak cytoplasmic AP-2 signal. As expected, p21 and p53 stainings were inversely related to each other (P < 0.001). There was a significant positive association between p21 and AP-2 expression levels (P= 0.01). p21 intensity and percentage were higher in Dukes' A and B stages (P< 0.001). The cancer-related survival and recurrence-free survival (RFS) rates were significantly lower among patients with a low signal for p21 (P< 0.001) and low p21 percentage in tumour epithelium (P < 0.001). High p53 staining intensity in tumour epithelium predicted poor survival (P = 0.01) and RFS (P = 0.003). In the multivariate analysis, p21 percentage distribution independently predicted cancer-related survival in all cases, and p21 expression intensity in T1-4/N0-3/M0 and T1-3/N0/M0 cases. p21 percentage distribution was an independent predictor of RFS in all and T1-3/N0/M0 cases. AP-2 staining did not reach any prognostic significance. These results suggest that the immunohistochemical detection of cyclin-dependent kinase inhibitor p21 could be used to predict more precisely the outcome of colorectal cancer patients.
Ropponen
K M
KM
Department of Pathology and Forensic Medicine, University of Kuopio, Kuopio University Hospital, Finland.
Kellokoski
J K
JK
Lipponen
P K
PK
Pietiläinen
T
T
Eskelinen
M J
MJ
Alhava
E M
EM
Kosma
V M
VM
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000096:biosynthesis*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53