ESTROGEN INCREASES S-PHASE FRACTION AND ESTROGEN AND PROGESTERONE RECEPTORS IN HUMAN CERVICAL-CANCER IN-VIVO

Although cancer of the cervix is traditionally considered not to be re sponsive to steroid hormones, an in vitro study has reported that the addition of oestrogen increased cellular proliferation in a cervix can cer cell line that was inhibited by progesterone. We investigated whet her the reported in vitro effects of oestrogen and progesterone on cel lular proliferation can be replicated in locally advanced cervical can cer in vivo and whether these effects, if any, are related to oestroge n and progesterone receptor (ER and PgR) content of the tumour. One hu ndred post-menopausal patients with locally advanced cervical cancer w ere systematically allocated by rotation to the four treatment groups: (1) control group receiving no treatment; (2) ethinyl oestradiol 50 m u g; (3) norethisterone 5 mg; (4) a combination of ethinyl oestradiol and norethisterone. Hormone treatment (five doses) was given orally ev ery 12 h. Tissue biopsies were taken before and 12 h after the last ho rmone treatment. S-phase fraction (SpF) was measured by flow cytometry , and ER and PSR were measured by enzyme immunoassay. Results were ana lysed using two-factor analysis of variance, the factors being oestrog en - absent or present - and progesterone - absent or present. The mai n effects of oestrogen were increases in SpF, ER and PgR, which were s tatistically significant (P = 0.0056, 0.0009 and 0.01 respectively), i ndicating that there is much greater change in these three parameters in the presence of oestrogen (mean changes 7.808 %, 6.258 fmol mg(-1) and 12.716 fmol mg(-1) for SpF, ER and PSR respectively) than in its a bsence (mean change -1.986 %, -3.041 fmol mg(-1) and 1.736 fmol mg(-1) respectively). The progestogen main effect and the oestrogen - proges togen interaction were not significant. The rise in SpF, ER and PSR in the presence of oestrogen had a correlation coefficient with the init ial ER values of -0.0565, -0.2863 and -0.1230 respectively, none being statistically significant, suggesting that the oestrogen actions were not strictly related to baseline ER concentrations. The combined medi an baseline ER and PSR values of the four groups were 1.48 fmol mg(-1) and 0.80 fmol mg(-1) respectively, Our results show that oestrogen is capable of increasing SpF in locally advanced cervical cancer in vivo and may help to revive interest in the use of oestrogen as a radiosen sitizing agent in the treatment of this disease.