Relationship between HPV typing and the status of G2 cell cycle regulators in cervical neoplasia.
We examined human papillomavirus (HPV) typing and the status of ATM, chk2, CDC25C, cdc2 and cyclinB1 in cervical intraepithelial neoplasia (CIN) and invasive cancer (IC). A total of 93 samples [normal: 10; CIN: 34 (CINI:9, CINII:12, CINIII:13); IC: 49 (stage I:10, stage II:21, stage III:15, stage IV:3)] were included in this study. HPV status was evaluated by the PCR non-radioactive HPV detection system. We analyzed ATM, chk2, CDC25C, cdc2 and cyclinB1 protein expression by immunohistochemistry. HPV DNA was detected in 73.5% of 34 CINs and 89.8% of 49 ICs. Detection of HPV subtypes 16 and 18 was more frequent in ICs (46.9%) than in CINs (23.5%) (p=0.0387). Abnormal expression of ATM, chk2, CDC25C, cdc2 and cyclinB1 were 2.9%, 32.4%, 2.9% 20.6% and 0% in CINs and 8.2%, 30.6%, 10.2%, 46.9% and 12.2% in ICs. The alteration of cdc2 was higher in ICs than in CINs (p=0.0198). Altered expression of cdc2 was higher in HPV16 and 18 cases (69.6%) than in other cases (26.9%) (p=0.0042). However, the relationship between HPV typing and ATM, chk2, CDC25C and cyclinB1 expression was not significant. Cdc2 is implicated in cervical carcinogenesis and may be related to p53 inactivation by HPV.
Department of Obstetrics and Gynecology, Osaka City General Hospital, 2-13-22 Miyako-jimahondori Miyakojima, Osaka 534-0021, Japan.
Yasunori
Y
Hashiguchi
Hiroshi
H
Tsuda
Sadako
S
Nishimura
Takeshi
T
Inoue
Naoki
N
Kawamura
Kumio
K
Yamamoto
D064007:Ataxia Telangiectasia Mutated Proteins; D016203:CDC2 Protein Kinase / Q000096:biosynthesis; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D064447:Checkpoint Kinase 2; D019926:Cyclin B / Q000096:biosynthesis; D056744:Cyclin B1; D004268:DNA-Binding Proteins; D005260:Female; D016195:G2 Phase; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D027383:Papillomaviridae / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000821:virology*; D020687:cdc25 Phosphatases / Q000096:biosynthesis; D002578:Uterine Cervical Dysplasia / Q000378:metabolism* / Q000821:virology*
C534699:CCNB1 protein, human; D018797:Cell Cycle Proteins; D019926:Cyclin B; D056744:Cyclin B1; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D064447:Checkpoint Kinase 2; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases