Five hundred twenty-six patients with invasive cervical cancer, treated at the University of Kentucky from 1964 to 1976, were followed 2-12 years after therapy. One hundred and sixty patients (3 1 %) developed tumor recurrence. Recurrent cancer was noted within 1 year after therapy in 58% of patients and within 2 years of treatment in 76% of patients. Only 6% of patients with recurrent cervical cancer survived 3 or more years. Stage of disease, cell type, lesion size, and the presence of lymph vascular space invasion by tumor cells were all shown to be prognostically significant. The addition of extrafascial hysterectomy to radiation therapy significantly decreased the incidence of recurrence in stage IB cervical tumors 5 cm or more in diameter. Analysis of this data suggests that radical hysterectomy and pelvic lymphadenectomy is as effective as irradiation only in the treatment of large cell squamous carcinomas 2 cm or less in diameter.Cancer 44:2 354 -236 1, 1979.

The human corpus luteum expresses genomic progesterone receptors (PRs) suggesting that progesterone may have an autocrine or paracrine role in luteal function. We hypothesised that the reduction in luteal PR reported in the late-luteal phase augmented progesterone withdrawal and had a role in luteolysis. We therefore tested the hypothesis that luteal rescue with human chorionic gonadotrophin (hCG) would maintain PR expression. PR was immunolocalised to different cell types in human corpora lutea (n 5 35) from different stages of the luteal phase and after luteal rescue with exogenous hCG. There was no change in the staining intensity of theca-lutein cell or stromal cell PR throughout the luteal phase or after luteal rescue. In the late-luteal phase, granulosa-lutein cell PR immunostaining was reduced (P < 0.05) but the trend to reduction was also seen after luteal rescue with hCG (P 5 0.055). To further investigate the effect of hCG on granulosa-lutein cell PR expression, an in vitro model system of cultured human luteinised granulosa cells was studied. Cells were cultured for 12 -13 days exposed to different patterns of hCG and aminoglutethamide to manipulate progesterone secretion (P < 0.0001). Expression of PR A/B and PR B isoforms was examined by quantitative real-time RT-PCR. PR A/B mRNA was lower (P < 0.05) after 11 -13 days of culture than after 7 days of culture. This reduction could not be prevented by hCG in the presence (P < 0.05) or absence (P < 0.05) of stimulated progesterone secretion. The expression of PR B mRNA showed a similar pattern (P 5 0.054). Simulated early pregnancy in vivo and hCG treatment of luteinised granulosa cells in vitro did not appear to prevent the down-regulation of PR seen during luteolysis.

Tumor markers in gynecologic malignancies can be classified generally as oncofetal proteins, carcino-placental proteins, and more specific tumor-associated antigens. Carcinoembryonic antigen (CEA) is most effective as a tumor marker in mucinous adenocarcinomas of the endocervix and ovary and in keratinizing squamous cell carcinomas of the cervix. In contrast, the use of alphafetoprotein (AFP) in gynecologic cancer is limited to patients with germ cell tumors of the ovary and specifically endodermal sinus tumors. The beta subunit of human chorionic gonadotropin (beta-hCG) remains an exemplary tumor marker for trophoblastic malignancies and may be useful in selected patients with epithelial carcinomas of the ovary. Plasma levels of these antigens are generally related to total tumor burden (tumor antigen concentration x extent of disease)). Although the lack of specificity of these markers has limited their use in the diagnosis of gynecologic malignancies, they have been effective as a means of monitoring disease status in patients whose tumors contain high antigen concentrations. More specific tumor-associated antigens have been described in ovarian cervical cancers, but their clinical efficacy remains to be demonstrated in large numbers of patients. Immunohistochemical staining of tissue specimens identifies patients whose tumors contain high antigen concentrations and who therefore should benefit most from serial plasma determinations following therapy. Potential future uses of biochemical markers include radioimmunodetection procedures using radiolabelled antibodies to tumor-associated antigens and antigen-directed chemotherapy.

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Immunoperoxidase staining for carcinoembryonic antigen (CEA) was performed on the tumors of 241 patients with invasive carcinoma of the cervix. Positive tissue staining indicative of a CEA concentration of at least 3 microgram/gm was present in 154 tumors (63%) as opposed to 0 of 30 specimens of normal cervix (p less than .001). Plasma CEA values were obtained at the time of tissue staining on all patients. Plasma CEA concentration was related more directly to total tumor burden (tumor CEA content x extent of disease) than to tumor CEA concentration alone. Progressively rising plasma CEA levels predicted recurrent disease in over 80% of patients whose tumors stained positively for CEA. In contrast, serial plasma CEA values correlated positively with clinical disease status in only 28% of patients whose tumors were devoid of CEA. Immunoperoxidase staining of tissue specimens identifies those patients whose tumors contain high levels of CEA and who therefore should benefit most from subsequent plasma antigen determinations.