A cell line designated RMG‐II was established from the ascites of a patient with ovarian clear cell carcinoma. The chromosomal analysis revealed aneuploidy with a hypertetraploid modal numher and 8 marker chromosomes. Radioimmunoassay and immunocytochemical staining showed that RMG‐II cells produced some tumor markers such as CA125 and TPA. Two monoclonal antibodies, designated MA602‐1 and MA602‐6, were generated by immunization of mice with an extract prepared from the culture supernatant of RMG‐II cells. The epitopes recognized by these two monoclonal antibodies were proved to differ from the CA125 epitope, but to exist on the molecule bearing CA125. We developed a double‐determinant sandwich enzyme imnnmoassay using these two monoclonal anti‐bodies, and the antigen defined by this assay was termed CA602. CA602 was frequently found in the sera of ovarian cancer patients; the positive rates were 92%, 38%, 60%, and 80% for serous, mucinous, clear cell, and endometrioid ovarian carcinomas, respectively, when the cut‐off value was set at 60 U/ml (=mean + 3SD of healthy females). CA602 levels in serum were also high in endometriosis patients and in early pregnancy, as is the case for CA125, and the correlation coefficient between CA602 and CA125 was high (r=0.88). Our preliminary evidence suggests that this CA602 assay system has higher sensitivity than the CA125 one.
Adenocarcinoma of the uterine cervix (CxAd) is one of the most distressing malignancies of the female reproductive system because of its tendency to spread aggressively and to be resistant to radiation and systemic therapies. To clarify the prognostic significance of p53 alteration in CxAd, we immunohistochemically examined the incidence of p53 nuclear accumulation, which is considered to be mostly parallel with p53 gene mutation, and its association with clinicopathological parameters in 26 patients with CxAd. The overall incidence of p53 nuclear accumulation was 46% (12 of 26), being higher in groups with clinically advanced disease, higher degrees of cellular atypia, and deeper myometrial invasion, but significantly lower in patients with integration of human papillomavirus (HPV) type 16 or 18 DNA. Nuclear p53 immunoreactivity as well as lymph node status, depth of invasion and the absence of HPV‐DNA integration were significant indicators of a poor prognosis. Examination of p53 nuclear accumulation could be applied to biopsy material, and would be of practical assistance in predicting the prognosis of CxAd both preoperatively and postoperatively.
Sera were examined for the presence of antibody against E7 protein of human papillomavirus type 16 (HPV‐16) by Western blot analysis using the bacterially derived unfused protein. The occurrence rates of anti‐E7 antibody against HPV‐16 were 14.1% (10/71) in cervical cancer patients, 0% (0/48) in cervical intraepithelial neoplasia patients, and 0% (0/41) in female non‐malignant patients. Three patients (one with endometrial cancer, one with breast cancer, and one male patient with colon polyp) out of 115 patients with tumors in organs other than the cervix, had antibody against E7 protein of HPV‐16. The serum antibody, once positive, could be detected for a long time after surgical removal of the cancers in all cases that could be followed up. HPV‐16 DNA could be detected in 50% (13/26) of cervical cancer patients. Sixty‐nine percent (9/13) of patients with HPV‐16 DNA in cancers had the antibody and all the patients with stages II, III, and IV cervical cancer (8/8) harboring HPV‐16 DNA showed the presence of the antibody against E7 protein of HPV‐16. In contrast, only 20% (1/5) of cervical cancer patients with stage Ia or Ib harboring HPV‐16 DNA showed positive for the anti‐E7 antibody in sera. These findings suggest that the presence of anti‐E7 antibody in serum depends on the staging of cervical cancer and extent of HPV infection.
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