Estrogen and progesterone receptors in epithelial ovarian malignancies

Cytoplasmic estrogen receptor levels (ER) were measured in ovarian epithelial malignancies from 44 patients using a dextran-coated charcoal assay with analysis of the data by Scatchard plots. In 31 cases, progesterone receptor levels (PR) were also determined. In untreated patients, 68.8% of malignancies were ER-positive (greater than or equal to 10 fmole receptor/mg protein) and 35.0% were PR-positive (greater than or equal to 50 fmole/mg protein). Receptor levels in ovarian epithelial malignancies were not dependent on patient age, menopausal status, tumor stage, or histologic grade. However, ovarian endometrioid carcinomas contained significantly more PR than other histologic variants (P less than 0.02). Excluding endometrioid carcinoma, tissues from patients treated with chemotherapy contained less ER and PR than tissues from untreated patients. ER-positive tumors from three patients assayed before cyclophosphamide or combination chemotherapy became ER-negative after therapy. In addition, tamoxifen increased cytoplasmic PR (124 to 333 fmol/mg) and decreased cytoplasmic ER (65 to 4 fmol/mg) in a single patient with endometrioid carcinoma.     

Importance of steroid receptors and aromatase activity in the prognosis of ovarian cancer: high tumor progesterone receptor levels correlate with longer survival

The presence of steroid receptors (82 tumors) and aromatase activity (39 tumors) in ovarian carcinomas was correlated with patient survival. No statistically significant correlation was found between the presence or absence of estrogen receptors (ER, 56.1%), progesterone receptors (PR, 57.3%), androgen receptors (AR, 91.5%), or aromatase activity (33.3%) and survival. However, high levels of PR were associated with better survival (P less than 0.05). Furthermore, there was a tendency for patients with advanced disease and PR-positive tumors to have better survival than those with advanced disease and PR-negative tumors (P = 0.13). Patients with tumors that did not contain any of the receptors and those in which ER and AR were absent, or in which PR and AR were absent, had poor survival. It is concluded that receptor status, especially of PR, may be of prognostic importance and that status of receptors and aromatase activity may become useful in selecting ovarian cancer patients for endocrine therapy.     

The relationship of steroid receptor expression to nuclear DNA distribution and clinicopathological characteristics in epithelial ovarian tumors

Tumor specimens from 92 patients with ovarian carcinoma were analyzed for estrogen receptor (ER), progesterone receptor (PR), proliferative fraction, and ploidy. Seventy-one percent of tumors were either ER+ (greater than 5 fmole/mg protein) or PR+ (greater than 10 fmole/mg protein) with 27% of tumors overall being both ER+ and PR+. There was no significant relationship between receptor expression and stage, grade, or histological subtype. Thirteen percent of diploid tumors were receptor negative in contrast to 38% of aneuploid tumors (P less than 0.01). There was no significant association between ER status and ploidy, but 60% of diploid tumors were PR+ in contrast to 33% of aneuploid tumors (P less than 0.02). Eleven percent of tumors overall were both ER rich and PR rich and comprised 23% of diploid and 5% of aneuploid tumors (P less than 0.01). Receptor-negative tumors had a median S phase of 18.8% which was significantly higher than the median S phase of 12% in receptor-positive tumors (P less than 0.02). A similar analysis was also performed on specimens from 9 patients with borderline epithelial ovarian tumors and 12 with benign epithelial ovarian tumors. Up to 50% of benign and borderline epithelial tumors had measurable receptors, but all were diploid with a relatively low S phase fraction. The functional significance of steroid receptor expression in ovarian cancer is unclear, but the association with ploidy and proliferative activity particularly in patients with malignant ovarian tumors may allow better identification of prognostic subsets and aid in selection of patients for hormonal therapy.     

Estrogen and progesterone receptors in endometrial cancer and their prognostic relevance

Three hundred and nine malignant endometrial tumors were biochemically analyzed with respect to estrogen (ER) and progesterone (PR) receptors. Fifty-seven percent of endometrial carcinomas were ER and PR positive (greater than or equal to 50 fmole/mg of cytosol protein); 24% were negative for both receptors. Five sarcomas and 16 of 21 mixed müllerian tumors were receptor negative. Receptor status correlated with clinical stage and grade of histological differentiation, but not with myometrial invasion. Anamnestic data on patients showed no differences between those with receptor-negative and receptor-positive tumors. Five-year survival rate (stage I) and median survival time (stages II-IV, recurrences) for patients with ER+/PR+ and ER-/PR+ endometrial cancer were significantly better than for ER-/PR- and ER+/PR- patients. A multivariate analysis demonstrated progesterone receptor as a significant prognostic factor next to clinical stage. Estrogen receptor had no significant prognostic relevance. A retrospective analysis of gestagen treatment and progesterone receptor status confirms the importance of PR, possibly independent of hormonal treatment.     

Correlation between nuclear DNA content and steroid receptor status in ovarian cancer

The nuclear DNA content of 47 malignant epithelial ovarian tumours and five ovarian tumours of borderline malignancy was correlated with estrogen (ER), progesterone (PR) and androgen receptor (AR) status. Aneuploidy was observed in 60% of the malignant tumours. The DNA index of poorly differentiated tumours was higher than that of well differentiated tumours (P less than 0.05). Ploidy did not correlate with histological type, stage of disease and ER content. Of the diploid tumours, 74% was PR-positive, in contrast to 36% of the aneuploid tumours (P less than 0.05). In addition, 89% of the diploid tumours had high AR levels (greater than or equal to 30 fmol/mg cytosol protein), in contrast to only 54% of the aneuploid tumours (P less than 0.05). These observations strengthen our previous findings on the prognostic importance of PR and also suggest that androgens may have a role in ovarian cancer.     

Cytoplasmic estrogen receptors in carcinoma of the uterine cervix

The concentration of cytoplasmic estrogen receptors (ER) in cancer of the uterine cervix was measured in 30 cases (28 squamous cell carcinomas and 2 adenocarcinomas). The mean ER concentration in squamous cell carcinoma was 19.3 +/- 26.0 fmol/mg cytosol protein; for pre- and postmenopausal women 6.82 +/- 9.86 and 28.6 +/- 30.1 fmol/mg protein, respectively, were found, the latter being significantly higher. When 'ER-positive' was defined as concentrations greater than 10 fmol/mg protein, 12 of the 28 cases (43%) were found to be ER-positive. There were no significant differences between the ER concentrations of clinical stage I and II squamous cell carcinomas (19.2 +/- 24.2 and 20.9 +/- 27.2 fmol/mg, respectively). ER were detectable in the cervical tissue from all of the control cases of myoma of the uterus. There were, however, no differences in the ER content between the proliferative and secretory phases, but the concentration in premenopausal women was significantly lower than that in postmenopausal women. In comparison with the controls, the mean ER level in both pre- and postmenopausal women with squamous cell carcinoma was significantly lower, due to the fact that ER were not detectable in 57% of these cases. Both cases of cervical adenocarcinoma were ER-positive.     

Estrogen and progesterone receptors in human ovarian tumors

Estrogen and progesterone receptors were measured in cystosols prepared from 32 normal ovaries and 25 benign and 49 malignant ovarian tumors. In normal ovarian tissue, estrogen and progesterone receptors were detected in 22 and 75% of specimens, respectively. Estrogen receptors were present in low concentrations ranging from 2 to 9 fmol/mg cytosol protein. The estrogen receptor content and distribution were similar in benign tumors (20%), but progesterone receptors were significantly decreased in 16% of specimens (P less than 0.001). In malignant ovarian tissues, estrogen receptors were present in 57% of specimens in concentration ranging from 1 to 132 fmol/mg cytosol protein. Of these, 72% of tissues had estrogen-receptor concentrations greater than 10 fmol/mg cytosol protein. The presence of estrogen receptors in ovarian cancer was significantly different from normal ovaries and benign tumor tissues (P less than 0.01). Progesterone receptors were detectable in 29% of ovarian cancer specimens. Estrogen and progesterone receptors were present alone or in combination, in 65% of ovarian cancers. The similarity in sex steroid content between ovarian and breast cancer warrants prospective studies of sex steroid receptor content in ovarian malignancies as a possible predictive index of survival and response to hormone therapy.     

卵巢上皮性肿瘤雌孕激素受体的单克隆抗体免疫组化研究

利用抗雌激素受体（ＥＲ）和孕激素受体（ＰＲ）的两种单克隆抗体对３１例卵巢上皮性肿瘤新鲜冰冻标本进行ＡＢＣ法测定，ＥＲ、ＰＲ的阳性表达率分别为４５．２％和４８．４％，恶性肿瘤ＥＲ的含量高于良性者，ＰＲ在良、恶性肿瘤间未见有明显差异。提示：部分卵巢上皮性肿瘤属于激素依赖性肿瘤，对晚期卵巢癌可试用激素疗法。ＥＲ、ＰＲ在宫内膜样癌和浆液性癌的含量高于其它类型上皮性肿瘤，高分化者受体阳性率及含量高于低分化者；ＥＲ或ＰＲＦ阳性者预后好于阴性者，二者具独立的预后因素，且ＥＲ、ＰＲ双阳性者预后比ＥＲ阳性、ＰＲ阴性或ＥＲ阴性、ＰＲ阳性者好。     

Estrogen and progesterone receptors in ovarian neoplasms

The cytoplasmic receptors for 17 beta-estradiol (ER) and progesterone (PR) were measured in 39 malignant and 15 benign ovarian neoplasms. All eight endometroid carcinomas had positive ER sites, one-half contained PR. The number of ER binding sites decreased as tumor grade increased. Conversely, none of the 11 mucinous tumors contained either ER or PR receptors. One-half of the well-differentiated serous tumors had ER (57 +/- 23 fmole/mg protein) while none of the poorly differentiated tumors had measurable binding. In serous carcinomas, PR was only detected in well-differentiated lesions (447 +/- 240 fmole/mg protein). Only one of 15 benign neoplasms contained ER and PR receptors. Correlation of tumor grade and type may help to plan hormonal therapies in advanced ovarian malignancies.     

Estrogen and progesterone receptors in tumors of the human ovary

A total of 23 malignant ovarian tumors and 5 benign or tumor-like lesions of the ovary had their estrogen receptor (ER) status, and of these 15 also had their progesterone receptor (PR) status, determined. Tumors were said to be ER+ when the receptors bound >4 fmole estradiol/mg protein and PR+ when they bound >10 fmole progesterone/mg protein. Ten of twenty-two ovarian carcinomas were estrogen receptor positive (ER+) and 3 of these also contained progesterone receptors (PR+). All 6 malignant ovarian tumors occurring in premenopausal women were ER? and PR? as were the two benign tumors occurring in two premenopausal patients. It may be that premenopausal women have tumors which are more frequently ER? PR? because their higher blood hormone levels block the estrogen and progesterone binding sites in the tissues. It was not possible to show any variation from normal in the plasma hormone levels (estradiol, estrone, testosterone, progesterone, FSH). It is suggested that hormone receptor studies of malignant ovarian tumors could aid in the selection of patients suitable for therapies based on endocrine manipulation.     

Estrogen and progestin receptor levels as prognosticators for survival in endometrial cancer

The survival of 213 postmenopausal patients with primary endometrial cancer was analyzed as a function of clinicopathologic features and cytosol steroid receptor levels. Estrogen receptor (ER) levels (P = 0.008) and progestin receptor (PR) levels (P = 0.0001) were negatively correlated with grade. ER and PR levels were positively correlated with each other (P = 0.0001), but neither was correlated with age. In 187 patients with stages I and II, ER positivity (greater than or equal to 20 fmole/mg cytosol protein (cp] was statistically associated with grade (P = 0.007); and PR (greater than or equal to 7 fmole/mg cp) was statistically associated with grade (P = 0.001). Univariant analysis revealed that survival for the early endometrial cancer patients was significantly dependent upon ER status (P = 0.0003), PR status (P = 0.0016), and grade (P = 0.0002). Multivariant analysis of ER status, PR status, age, and grade showed that the ER status was a significant prognostic factor for survival (P = 0.0168), even if the positivity of the PR status was defined at greater than or equal to 50 fmole/mg cp. If ER status was divided at 0-19, 20-100, and greater than 100 fmole/mg cp, survival was significantly different between the low range group and the other two groups. If PR status was divided at 0-6, 7-50, and greater than 50 fmole/mg cp survival was significantly different between the first two groups and the high range group. Thus, survival in these endometrial cancer patients was better predicted by ER status than grade.     

Estrogen - and gestagen - receptors in ovarian carcinoma

Estrogen (ER) - and progestagen (PgR) - receptors were estimated by a DCC method using Scatchard plot analysis In tissue samples of 68 patients with ovarian carcinomas. The mean ER and PgR levels were at 52 and 74 fmol/mg cytosol protein, respectively. ER+ PgR+ records were noted in 32.4%, ER+ PgR- in 26.4%, ER- PgR+ in 7.4%, and 33.8% presented with ER- PgR-. In the surviving group 44.1% had Er+ PgR+, whereas the patients who died had an incidence of only 20.5% ER+ PgR+. In addition, the incidences of ER+ PgR+ in stage I plus II and stage III plus IV patients were 42.6 and 29.5%, respectively. Furthermore, higher incidences of ER+ PgR+ were recorded in patients older than 60 years of age (63%) than in younger subjects (36%). The present data combine to suggest that receptor assays should become a useful tool in the management of patients bearing ovarian carcinomas. In addition, ER and PgR determinations provide a prognostic index and may improve the possibility to predict which well-differentiated stage I ovarian carcinomas are likely to recur.     

Steroid receptor content in human ovarian tumors: survival of patients with ovarian carcinoma related to steroid receptor content

Steroid receptors were measured in 31 malignant and 29 benign or semimalignant ovarian tumors in a prospective study. Estrogen receptors (ER) were found more often in highly differentiated malignant tumors (86%) than in poorly differentiated ones (23%). No such difference was found for progesterone receptor (PR). Receptor content was not related to clinical stage. The median survival of patients with PR+ or ER+/PR+ malignant tumors was 30 and 31.5 months, respectively, compared to 10 and 9 months for those with receptor negative tumors. This positive prognostic information could not be demonstrated for ER alone. Receptor content and distribution were similar in benign and semimalignant tumors. Measurement of hormone receptors in ovarian cancers can thus give valuable prognostic information.     

Steroid receptors in ovarian carcinoma: Immunohistochemical determination may lead to new aspects

87 nonpretreated stage III/IV ovarian common epithelial carcinomas were studied for estrogen receptor (ER) and progesterone receptor (PR) content by both immunohistochemistry (IHC) and biochemical (DCC) analysis. While the DCC assay showed tumors to be receptor-positive in 62% (ER) and 66% (PR), receptor-positive malignant epithelial cells were only detected in 38% (ER) and 31% (PR) by IHC. There was only a low correlation between the semiquantitative results of ER and PR IHC and the corresponding values of DCC receptor determination. The finding of steroid receptor-positive stromal cells without any evidence of hormone receptor-positive epithelial tumor cells offers a possible explanation for discrepant results in numerous cases with obviously "false positive" results of DCC analysis. Since the considerable heterogeneity of steroid receptor expression present in many ovarian neoplasms can only be detected by IHC, it seems to be the appropriate method of ER and PR determination. Most patients were treated by both radical cytoreductive surgery (n = 76) and a platinum-based chemotherapy (n = 79). ER was not shown to be of significant prognostic value. However, survival was significantly better in patients with PR positive tumors (IHC and DCC) on univariate analysis. Residual tumor after primary surgery was the only remaining significant prognostic factor after multivariate analysis. Further studies are needed to clarify the biological function of steroid receptor-positive stromal cells in ovarian carcinomas.     

Expression of epidermal growth factor receptors in benign ovarian tumors

The objective of the present study was to determine the level of EGFR expression in patients having benign ovarian tumors and in morphologically normal ovarian tissue by quantitative ligand binding assays. In a prospective study 42 patients with benign ovarian tumors and 30 with normal ovaries were included. In the group of patients expressing EGFR, those having benign tumors were 23 (64%) and the ones with normal ovaries--13 (36%). The average level of EGFR expression was the highest in the cases of teratoma adultum (110 fmol/mg), followed by mucinous (97 fmol/mg) and serous (30 fmol/mg) cystadenomas. The differences between the average levels of EGFR expression in mucinous and serous benign ovarian tumors were significant (p = 0.032), as for the remaining histological variants--statistically insignificant (p = 0.086). Mucinous cystadenomas possessed higher proliferative potential compared to serous cystadenomas.     

Clinical correlation of hormone receptor status in epithelial ovarian cancer

Cytoplasmic estrogen receptor (ER) and progesterone receptor (PR) levels were measured in ovarian epithelial carcinomas from 37 patients using a dextran-coated charcoal assay prior to any treatment. Sixty-eight percent of the tumors were ER positive, forty-nine percent were PR positive, forty-one percent were positive for both receptors, and twenty-seven percent were negative for both receptors. Receptor status in epithelial ovarian carcinomas was found to have no clinical significance when correlated with age, parity, race, cigarette smoking, surgical stage, histologic type, histologic grade, progression-free interval, or patient survival.     

The distribution and prognostic implications of steroid receptors in endometrial carcinomas

Estradiol receptors (ER) were measured in 71 and progesterone receptors (PR) in 62 primary endometrial carcinomas. ER were found in 62 (87%) and PR in 56 (90%) of the tumors. Fifty-six tumors were ER+/PR+ and 4 were ER-/PR-. The frequency of receptor positive tumors was not significantly correlated to histological grade. Highly differentiated tumors were, however, more often ER and PR rich (greater than or equal to 30 fmole/mg protein) as compared to poorly differentiated tumors. The median ER and PR values for grade I tumors were also significantly higher than for grade III tumors. No significant differences were found in the frequency of patients with ER or PR rich tumors in the different FIGO or surgical stages. The receptor status was not related to depth of myometrial infiltration. Recurrence rates and death rates were significantly higher in patients with PR poor as compared to those with PR rich tumors. This prognostic information could not be shown for ER.     

Relation of estrogen receptor expression in endometrial cancer specimens to bone mineral density

BACKGROUND: To investigate the relation of estrogen and progesterone receptor (ER and PR) expression in endometrial cancer specimens to bone mineral density (BMD). MATERIALS AND METHODS: Subjects were 48 postmenopausal women with endometrial cancer treated with hysterectomy. Baseline characteristics included age, years since menopause (YSM), height, weight, and body mass index (BMI). Lumbar spine BMD (L2-4), the ratio of trunk fat to leg fat mass (trunk-leg fat ratio), body fat mass, and the percentage of body fat were measured by dual-energy x-ray absorptiometry (DEXA). ER and PR expression in endometrial cancer specimens were determined immunohistochemically. RESULTS: Of 48 women, 32 (66.7%) were ER/PR-positive, nine (18.8%) were ER/PR-negative, three (6.3%) were ER-positive/PR-negative, and four (8.3%) were ER-negative/PR-positive. Lumbar spine BMD and trunk-leg fat ratio were significantly higher in women with ER-positive than in those with ER-negative (p<0.05), but other variables did not differ between the two groups. BMD and baseline- and anthropometric characteristics did not differ between the two groups divided by the presence or absence of PR expression. CONCLUSIONS: ER expression in endometrial cancer specimens is associated with higher lumbar spine BMD.     

Localization of sex steroid hormone and sex steroid hormone receptors in human ovarian epithelial tumor

In some ovarian tumors, such as endometrioid adenocarcinoma, dysfunctional uterine bleeding occurs, and the endocrinological aspects were studied in the following way: 1) In 3 patients with epithelial ovarian tumor and postmenopausal uterine bleeding, preoperative plasma estradiol (E2) and progesterone (P) concentrations were significantly high, but dropped to normal following complete resections of the ovarian tumor. Plasma E2, P and testosterone concentrations in ovarian veins were 3 to 7 times as great as in peripheral veins. 2) Tissues obtained from 25 ovarian tumors were immunohistochemically examined by the PAP method. In 9 cases of endometrioid adenocarcinoma, positive stainings for both E2 and P were demonstrated in cancer cells from 3 patients (33%) and in connective tissues from 7 patients (78%), respectively. In contrast, 16 tumors of other histological types gave only one positive staining for E2 on cancer cells and connective tissues. As for P, in 3 patients there was a positive stain on cancer cells and in 2 patients on connective tissues. 3) Five out of 8 patients with immunohistochemically positive staining for E2 on connective tissues in ovarian tumors demonstrated dysfunctional uterine bleeding. 4) Cytosolic estrogen receptor (ER) and progesterone receptor (PR) in ovarian tumors obtained from 26 patients were measured by the DCC method. All of three patients with endometrioid adenocarcinoma had both ER and PR. The former were 19-202 fmol/mg, and the latter 535-1,000 fmol/mg, which were significantly higher levels and positive rates than those from other patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Occurrence of epidermal growth factor receptors in human adnexal tumors and their prognostic value in advanced ovarian carcinomas

Ninety-eight different malignant adnexal tumors were analyzed for the presence of epidermal growth factor (EGF)-specific binding sites and binding parameters were calculated by Scatchard plot analysis [G. Scatchard, Ann. N.Y. Acad. Sci. 51, 660-672 (1949)]. Thirty-four biopsies were EGF receptor (EGF-R) positive with dissociation constants (KD) of 0.5-12 X 10(-9) M and binding capacities (Bmax) of 2-250 fmol/mg. One tumor had a KD of 60 X 10(-9) M and a Bmax of 1660 fmol/mg. The correlation of EGF-R status with clinical parameters showed no significant differences in primary, metastatic, or recurrent tumors, histological subtype, tumor differentiation, and tumor residual after primary surgery. As an inverse correlation, EGF-R-positive tumors are 39% and EGF-R-negative tumors 60% progesterone receptor positive. A response to chemotherapy was noticed in 50% of EGF-R-positive ovarian carcinomas with a mean survival time of patients of 28 months. The response rate of EGF-R negative ovarian carcinomas was 12% with a mean survival time of 16 months. Regarding the treatment schedule the major differences were noticed in the cis-platinum plus cyclophosphamide treatment group. These results suggest that the biology of ovarian carcinomas is influenced by growth factors and their receptors, which can be used as prognostic factors.