The importance of biological factors (bcl-2, bax, p53, PCNA, MI, HPV and angiogenesis) in invasive cervical cancer.
OBJECTIVE
The present study was designed to analyse the relationship between apoptosis related proteins (bcl-2 and bax), tumour suppressor protein p53, proliferation markers (PCNA and mitotic index), human papillomavirus (HPV) and angiogenesis in cervical cancer and their impact on clinical outcome.


METHODS
Tumours from 111 patients were assessed by immunohistochemistry for the expression of bcl-2, bax, p53 and PCNA, by PCR for the presence of HPV-DNA, for the quantification of the mitotic index and the microvessel density (CD 31). The results were correlated with various histopathologic characteristics and survival.


RESULTS
The multiple Cox's regression analysis for overall survival of all prognostic variables gave as best model: bcl-2 (P<0.001), lymphovascular permeation (P=0.004), mitotic index (P=0.019), tumour grade (P=0.048) and FIGO stage (P=0.070). Subanalysis was performed for the patients where the lymph node status was known (n=79). Adding the lymph node status gave as best model for overall survival bcl-2 (P=0.001), lymphovascular permeation (P=0.003) and mitotic index (P=0.044). However, they hardly influenced the association.


CONCLUSIONS
In the apoptotic pathway of cervical cancer, bcl-2 is one of most important proteins. It can probably not only mediate cell death but also regulate cell growth. A better understanding of their relations will probably provide the basis for more rational cancer therapies in the future.
Tjalma
W A
WA
Laboratory of Cancer Research and Clinical Oncology, Antwerp University, Antwerp, Belgium. wiebren.tjalma@uza.uia.ac.be
Weyler
J J
JJ
Bogers
J J
JJ
Pollefliet
C
C
Baay
M
M
Goovaerts
G C
GC
Vermorken
J B
JB
van Dam
P A
PA
van Marck
E A
EA
Buytaert
P M
PM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008833:Microcirculation / Q000473:pathology; D008875:Middle Aged; D008940:Mitotic Index; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D027383:Papillomaviridae / Q000235:genetics; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D016133:Polymerase Chain Reaction; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D012044:Regression Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D002583:Uterine Cervical Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D004279:DNA, Viral; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein