The possible role of bcl-2 expression in the progression of tumors of the uterine cervix.
BACKGROUND
A close link between human papillomavirus (HPV) and the development of uterine cervical neoplasias has been proposed. However, other cofactors also are required for malignant transformation.


METHODS
Forty-six cervical intraepithelial neoplasias (CIN) I/II, 75 CIN III, and 60 invasive squamous cell carcinomas (ISCC) were investigated by immunohistochemical staining for bcl-2 protein (bcl-2), bax protein (Bax), estrogen receptor (ER), and progesterone receptor (PR). The presence of HPV-DNA was examined using the polymerase chain reaction assay.


RESULTS
bcl-2 immunoreactivity was found in 17 of 46 (37%) CIN I/II, 48 of 75 (64%) CIN III, and 12 of 60 (20%) ISCC, the positivity in CIN III being significantly higher than in CIN I/II or ISCC (P < 0.004, P = 0.0001). The bcl-2 immunostaining pattern could be subdivided into two groups, basal type and diffuse type, with the incidence of the latter being clearly increased, in line with tumor progression. In the Bax or HPV-DNA positive groups, bcl-2 positive cases in CIN I/II were in the minority, whereas in CIN III they constituted the majority. In ISCC, bcl-2 positive was significantly lower than negative cases, not being associated with Bax and HPV-DNA. Estrogen receptor and PR immunoreactivity were rare.


CONCLUSIONS
These results indicate that bcl-2 may play an important role in a relatively early stage of cervical tumorigenesis, in association with Bax expression and HPV infection.
Saegusa
M
M
Department of Pathology, School of Medicine Kitasato University, Kanagawa, Japan.
Takano
Y
Y
Hashimura
M
M
Shoji
Y
Y
Okayasu
I
I
D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology / Q000821:virology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D003043:Cocarcinogenesis; D004279:DNA, Viral / Q000032:analysis; D018450:Disease Progression; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000235:genetics / Q000473:pathology; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D011519:Proto-Oncogenes / Q000235:genetics*; D011960:Receptors, Estrogen / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics; D014412:Tumor Virus Infections / Q000235:genetics / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D051028:bcl-2-Associated X Protein; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000473:pathology / Q000821:virology
C494826:BAX protein, human; D004279:DNA, Viral; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D051028:bcl-2-Associated X Protein; D011505:Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins