The p53 gene, located on chromosome 17p13, acts as a tumor suppression gene and encodes a 53kd nuclear phosphoprotein composed of 393 amono acid. P53 has been implicate in controlling cell cycle progression at the G1-S transition, and absence or
mutant
of p53 gene is related to tumor progression by entering S-phase before repairing DNA damage. In cervical cancer, inactiviation of p53 theoretically could occur by two mechanisms. The E6 transforming protein of oncogenic human papillomavirus(HPV)
binds
to and promotes the degradation of p53, or the mutation of the p53 gene could result in its inactivation.
The present study was undertaken to characterize p53 mutations and HPV infection status in the primary site and metastatic lymph node, and to investigate the possible role of the p53 gene in the advance and metastases of cervical cancer.
This study included 40 stage I/II cervical cancer patients, 20 of whom had no lymph node metastases, and remaining 20 patients had more than 3 metastatic lymph nodes. They initially received radical hysterectomy and pelvic lymph node dissection
at
the
Seoul National University Hospital from 1989 to 1990. Paraffin embedded tissue blocks of primary cervical cancer and metastatic lymph node were obtained in patients without node metastases. The PCR and Southern blotting were used for the
detection
of
HPV 16/18 DNA. The applied methods for detection of p53 mutation was immunohistochemistry (IHC), and polymerase chain reaction with single stranded conformation polymorphism (PCR-SSCP) after amplification of single exon sequences by PCR, from
exons
5 to
8 of the p53 gene.
Among 20 patients with no lymph node metastases, only 4 had positive immunohistochemical staining for p53. In patients with lymph node metastases, 10 of 20 primary site samples and 12 of 20 metastatic lymph node samples showed positive results in
immunohistochemical staining
Among cases with lymph node p53 overexpression, 6 cases had negative p53 staining in the primary site. In PCR-SSCP analysis, mutations were found in only two cases of primary site and one sample from metastatic lymph node in patients with nodal
metastases. Inverse relationship between p53 overexpression and HPV DNA positivity was not found.
HPV status in primary and metastatic site strongly suggest that HPV is associated with cervical cancer. The acquisition of p53 mutations is associated with tumor progression and some cases of metastases irrelevant to HPV infection in cervical
cancer.
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