Expression of p27, cyclin E and cyclin A in hepatocellular carcinoma and its clinical significance.
OBJECTIVE
To investigate the expression of p27, cyclin E and cyclin A in hepatocellular carcinoma (HCC) and its potential clinical significance.


METHODS
Expression of p27, cyclin E and cyclin A in 45 HCC specimens and 30 adjacent noncancerous lesions obtained from 45 patients during surgery was examined by immunohistochemical SABC assay. The diameter of tumor ranged from 1 cm to 19 cm (d< or =5 cm, 9 samples; 5 cm<d< or =10 cm, 19 samples; d>10 cm, 17 samples). The tumors were graded according to the criteria described by Edmondson-Steiner: well-differentiated HCC group (Grade I+II), 26 samples; poorly-differentiated HCC group (Grade III+IV), 19 samples. According to the clinical-pathologic features, 19 samples were poorly encapsulated, 15 samples had portal invasion of cancer, 11 samples had extrahepatic metastasis, and 12 samples had intrahepatic metastasis. All of the samples were classified as the invasive and metastatic group, while the remaining was classified as the non-invasive and non- metastatic group.


RESULTS
The average labeling index (LI) of p27 in HCC lesions was significantly higher than that in adjacent noncancerous lesions (45.87+/-14.21 vs 33.77+/-12.92, t=3.745, P<0.001). The LI of p27 was associated with differentiation, invasiveness and metastasis of the tumors (34.46+/-12.29 vs 52.80+/-11.36, t=5.17; 41.42+/-12.86 vs 51.44+/-14.10, t=2.48; P<0.05). Cyclin E was overexpressed in 16 cases (35.6%) while cyclin A was overexpressed in 21 cases (46.7%) in HCC lesions. No overexpression of cyclin E or cyclin A could be observed in adjacent non-carcinoma lesions and normal liver tissues. The overexpressions of cyclin E and cyclin A were correlated with differentiation, tumor thrombus, invasiveness and metastasis (P<0.05). Expression of cyclin E was significantly correlated with expression of cyclin A (r=0.329, P<0.05). The LI of p27 was significantly decreased in cyclin E, cyclin A positive groups (40.33+/-11.91 vs 49.50+/-13.76, t=3.05; 38.86+/-11.19 vs 52.57+/-12.62, t=3.89; P<0.05).


CONCLUSIONS
p27, cyclin E, cyclin A play cooperative roles in HCC tumorigenesis, differentiation, invasiveness and metastasis. Detection of their expression may be helpful in prediction of tumor progression.
Zhou
Qi
Q
Department of Hepatobilliary Surgery, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guandong Province, China.
He
Qiang
Q
Liang
Li-Jian
LJ
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D019925:Cyclin A / Q000378:metabolism*; D019927:Cyclin E / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011237:Predictive Value of Tests; D011379:Prognosis; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D019925:Cyclin A; D019927:Cyclin E; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27