Hepatocellular carcinoma--survival and clinical characteristics in relation to various histologic molecular markers in Western patients.
BACKGROUND
Many genes participate in the regulation of cell proliferation and growth of tumor cells. Altered expression and loss of function of some of these gene products have been found in malignant tumors and correlated with progression and poor prognosis.


OBJECTIVE
Our aim was to correlate the expression of various molecular histologic markers with tumor characteristics and survival time of patients with hepatocellular carcinoma (HCC).


METHODS
Tumor tissues of 81 patients with HCC were investigated immunohistochemically for the expression of cellular proliferation markers Mib1 (Ki67) and c-erbB-2 (HER2/neu), cellcycle markers (p53, mdm2 and p21), CD81 (TAPA1), a marker shown to be associated with metastasis, and human leukocyte antigen (HLA)-DR expression, involved in immunological antigen presentation.


RESULTS
p21 was expressed in a higher percentage (83.3 vs. 50%, P=0.014) in undifferentiated histological tumor grades (Edmondson Steiner G3 vs. G1/G2). HCC in patients with enlarged lymph nodes expressed HLA-DR in a higher percentage (28.6%) than tumors without lymph node enlargement (5.7%, P=0.006). Patients with distant metastases were less likely to express CD 81 (11.1%) on tumor cells than patients without distant metastases (38.3%, P=0.0335). No other correlation with clinical or tumor characteristics or molecular histologic markers investigated was found. P53 accumulating patients showed a worse survival than patients with tumors p53 non-accumulating (median 4.1 months vs. median 9.3 months, P=0.01798). Neither the expression nor the non-expression of proliferation, cell cycle, immunologic or cell adhesion markers was associated with differences in survival. However, patients with a low expression of cell cycle marker mdm2 survived significantly longer (median 9.4 months) as compared with patients with high expression (median 3.9 months).


CONCLUSIONS
Our results suggest that p53 nuclear accumulation and mdm2 high expression are associated with poor survival in patients withHCC. Furthermore, patients with enlarged lymph nodes had HLA-DR-positive tumors more frequently and patients with distant metastases had tumors with CD81 expression less often.
Schöniger-Hekele
Maximilian
M
Universitätsklinik für Innere Medizin IV, Klinische Abteilung Gastroenterologie und Hepatologie, University of Vienna, A-1090 Vienna, Austria.
Hänel
Sabine
S
Wrba
Fritz
F
Müller
Christian
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D001317:Austria / Q000453:epidemiology; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000401:mortality* / Q000556:secondary; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015996:Survival Rate; D060225:Tetraspanin 28; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D015703:Antigens, CD; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D006684:HLA-DR Antigens; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D051736:Proto-Oncogene Proteins c-mdm2; D018719:Erb-b2 Receptor Tyrosine Kinases; D060225:Tetraspanin 28; D016159:Tumor Suppressor Protein p53; C554798:CD81 protein, human; C493956:CDKN1A protein, human; C497206:MDM2 protein, human