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.     

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。     

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.     

子宫内膜癌的微卫星不稳定性与临床病理和雌、孕激素受体水平的关系

目的 探讨子宫内膜癌『微卫星不稳定性（ｍｉｃｒｏｓａｔｅｌｌｉｔｅ ｉｎｓｔａｂｉｌｉｔｙ,ＭＩ）的发生及其与各临床病理参数和雌激受体（ＥＲ）、孕激素受体（ＰＲ）水平的关系。方法 采用聚合酶链反应（ＰＣＲ）、变性聚丙烯酰胺凝胶电泳等技术,在８个位点上对４０例散发性子宫内膜癌病人进行ＭＩ测定。以免疫组织化学法检测了２７例病人的ＥＲ、ＰＲ水平,并比较ＭＩ与临床病理参数和ＥＲ、ＰＲ水平的关系。结果 ９例     

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.     

Cytoplasmic progesterone and estradiol receptors in normal, hyperplastic, and carcinomatous endometria: therapeutic implications

This study was designed to determine whether the presence of progesterone receptors (PR) and/or estradiol receptors (ER) could be used to predict progestin responsiveness of recurrent or advanced endometrial cancers. We have demonstrated the presence of physicochemically similar cytoplasmic progesterone and estradiol receptors in normal, hyperplastic, and carcinomatous endometria. All normal endometria contained both PR and ER. Seventy-three percent of endometrial hyperplasias were PR(+) and 93% were ER(+). A decreasing concentration of progesterone receptor activity was observed with increasing tumor anaplasia [grade 1, 84% PR(+); grade 2, 55% PR(+); grade 3, 22% PR(+)] and in irradiated tumors. A statistically significant (p less than 0.001) relationship has been demonstrated between the presence of specific cytoplasmic PR and response to progestin therapy in recurrent or advanced endometrial adenocarcinomas. Thus, we conclude that a PR assay may be used to help select the most appropriate therapy for patients with recurrent or advanced endometrial adenocarcinoma.     

卵巢肿瘤组织雌、孕激素受体测定

用葡聚糖—活性炭吸附法测定14例正常卵巢、14例良性卵巢肿瘤和44例卵巢恶性肿瘤的胞浆雌、孕激素受体(EcR、PcR)和胞核孕激素受体(PnR)。结果显示恶性卵巢肿瘤的EcR中位数、EcR阳性率及EcR、PcR双阳性率均高于其他两组,EcR、PcR双阴性率低于其他两组。PnR的测定结果与PcR的结果一致。高分化卵巢癌的EcR及PcR含量高于低分化肿瘤,作者认为一部分卵巢肿瘤存在ER、PR,提供了内分泌治疗奏效之可能,应用受体测定可防止激素治疗的盲目性。     

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.     

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.     

Correlation between steroid hormone receptors, histological and clinical parameters in ovarian carcinoma

Estrogen (ER) and progesterone (PR) receptors in ovarian tumors of 62 patients (51 carcinomas, 11 benign tumors) were estimated by the dextran-coated charcoal method using Scatchard plot analyses. 63% of carcinomas were ER-positive (greater than 10 fmol/mg cytosol), 38% were PR-positive (greater than 25 fmol/mg cytosol), whereas in benign tumors only 45% were ER-positive and 36% were PR-positive. We found no statistically significant correlation between receptor content and stage of disease, menopausal status or age of the patient. The highest concentration of ER and PR was observed in patients between 61 and 70 years of age. Life table analysis for patients with advanced ovarian carcinomas showed no significant difference in survival time in the group with higher ER and PR content. This study also reports the results obtained in a group of patients with receptor-positive ovarian carcinomas treated with a combination of chemotherapy and antiestrogen therapy. In comparison to treatment with cytotoxic chemotherapy alone, no significant difference in the time of survival or duration of remission could be found.     

Level of estrogen receptors (ER) as a function of histological malignancy stages of tumors in patients with breast neoplasm]

The presence of estrogen receptors (ER) has been studied in 70 patients with primary operable breast cancer. The tumors were graded histologically according to Bloom and Richardson criteria. A significant correlation was found between these two prognostic factors: the better--differentiated tumors (I + II histological grade) had significantly higher level of ER than that in the poor--differentiated tumors. Estrogen receptor content of primary breast cancer as a function of tumor grade can be useful in selection of the most efficient treatment modalities for individual patients.     

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.     

Relationship of estrogen and progesterone receptors to clinical outcome in metastatic endometrial carcinoma: a Gynecologic Oncology Group Study

INTRODUCTION: The goal of this study was to explore the relationship between the expression of hormone receptors in metastatic endometrial tumors and clinical response to daily tamoxifen citrate and intermittent weekly medroxyprogesterone acetate. STUDY DESIGN: Patients with measurable recurrent or advanced endometrial cancer were enrolled on a clinical trial, Gynecologic Oncology Group Study 119. A pretreatment tumor biopsy was obtained and subjected to immunohistochemical analyses. Estrogen receptor-alpha (ER-alpha) and progesterone receptor (PR) were assessed on frozen tissues, and PR isoforms A and B were detected on fixed tissues. The receptors were scored using a semi-quantitative HSCORE, with a cut off greater than 75 considered positive. RESULTS: Of the 60 eligible patients, 45 had evaluable tissues for all receptors. For ER, 40% of the cases were positive; for PR, 45% were positive. The sub-cellular distribution of PRA was exclusively nuclear, and 16% of the tumors demonstrated positive staining. PRB was nuclear and cytoplasmic, with 22% of the tumors staining for nuclear PRB and 36% of the tumors staining for cytoplasmic PRB. ER and PR from frozen tissues and PRA and cytoplasmic PRB from fixed tissues significantly decreased with increasing tumor grade. The co-expression of ER-alpha with PR from the frozen tissues (r=0.68, p<0.001) and PRA (r=0.58, p<0.001) from the fixed tissues was statistically significant. The ER HSCORE was related to both response and overall survival; there was no statistically significant correlation of PR with clinical response in this small number of patients. CONCLUSION: ER-alpha measured in metastatic endometrial carcinoma tissue prior to hormonal therapy was statistically significantly related to clinical response to daily tamoxifen and intermittent medroxyprogesterone acetate.     

Steroid hormone receptors in carcinoma of the cervix: lack of response to an antiestrogen

Levels of estrogen (ER) and progesterone (PR) receptors were measured in 81 patients with primary cervical cancer. In 10 patients, receptor levels were evaluated before and after a short course of tamoxifen treatment. Fifty-six percent of cervical tumors contained ER, and 58%, PR. Receptor level and expression were not related to any clinical and histological characteristic. Moreover, both survival time and response to neoadjuvant chemotherapy did not correlate with the presence of ER and PR. Tamoxifen treatment did not influence ER and PR levels. Our results suggest that steroid hormone receptors are of little value in the management of cervical cancer, and that in this neoplasia, ER is probably not functional.     

卵巢癌DNA水平、S期比例、雌孕激素受体与临床病理组织学的关系

测定了２４例卵巢癌标本的ＤＮＡ水平、Ｓ期比例（ＳＰＦ）及雌、孕激素受体（ＥＲ、ＰＲ），分析了它们之间以及与临床病理组织学之间的关系。结果表明，卵巢癌ＤＮＡ水平、ＳＰＦ与有无腹水及病理分级有明显的关系；二倍体组的ＰＲ阳性率明显高于异倍体组；二倍体组的ＳＰＦ明显低于异倍体组；ＥＲ（－）ＰＲ（－）组的ＳＰＦ明显高于ＥＲ（＋）ＰＲ（＋）组。提示卵巢癌ＤＮＡ水平和ＳＰＦ可作为一个相对独立的反映卵巢癌生物学行为的客观指标，对估计卵巢癌的预后和选择治疗方案有较大的价值。     

Estrogen and progesterone receptor assay in carcinoma of the cervix with monoclonal antibodies

The normal cervix has been shown to contain estrogen and progesterone receptors (ER and PR), but there have been controversial reports on the presence of these receptors in cervical carcinoma. Thus to explore the relationships between the steroid receptor status and cervical carcinoma, tissues of 34 patients with invasive cervical carcinoma prior to treatment and 30 cases of control who underwent hysterectomy due to benign gynecologic diseases at Yonsei Medical Center were analyzed for ER and PR using immunocytochemical assay with monoclonal antibodies and the results were compared with those of conventional steroid binding assay. ER and PR were positive in 65 and 71% of all tumors, respectively, and 59% of the cases were positive for both receptors simultaneously. No significant difference in receptor levels was noted when stratified according to menopausal status or clinical stage. With regard to tumor size, lesions greater than 3 cm had significantly lower receptor positivity when compared with the control. For the histological cell types, a statistically significant higher mean ER level was noted in adenocarcinoma compared to squamous cells. Even though the potential therapeutic significance of these findings is not yet known, they are consistent with the concept that steroid receptors can be used as a guide to endocrine therapy with respect to other prognostic parameters. However, the small number of advanced-stage carcinomas and the absence of data regarding survival rate in this study preclude any definite conclusions.     

Influence of HSP27 and steroid receptor status on provera sensitivity, DNA-ploidy and survival of females with endometrial cancer

Heat shock protein (HSP) 27, estradiol (ER), progesterone (PR), isocitric dehydrogenase and DNA-ploidy have been measured in 152 endometrial adenocarcinomas. These parameters have also been related to each other and to tumor grade and overall patient survival. HSP27 was assessed immunohistochemically and ploidy by FACS analysis, whilst biochemical methods were used for the other assays. HSP27 was significantly correlated with ER but not PR, grade or ploidy. Both ER and PR were related to tumor grade but not ploidy. Provera (2–14 days, mean 8) had no apparent effect on HSP27 staining but induced isocitric dehydrogenase in 70% of the tumors. Provera decreased ER (64%) and PR (70%) content in originally positive tumors. The presence of either HSP27, ER or PR in the pretreatment sample was significantly associated with provera induction of isocitric dehydrogenase activity; neither tumor grade nor ploidy predicted for induction of this enzyme. High levels of either HSP27, ER, PR or provera-induced isocitric dehydrogenase and diploid DNA were associated with good overall survival, whereas aneuploidy was linked with poor survival.     

Hydrophobic DNA adducts in relationship to estrogen and progesterone receptors content in human uterine cancer.]

OBJECTIVE: Determination of the relationship between hydrophobic DNA adducts (A) and estrogen receptors (ER) and progesterone (PR) receptor status in uterine cancers. METHODS: Using the P1 enriched version of 32P-postlabeling for hydrophobic DNA adducts detection on polyethyleneimine (PEI) cellulose thin layer chromatograms (TLC) we examined 11 uterine cancer DNAs. The quantification of the adducts was performed by Cerenkov counting of the spots. ER and PR status was recognized histochemically and H-score estimate was performed for each investigated cancer tissue. Patterns of uterine cancer DNA adducts were compared to the maps of adducts recognized in normal human endometrium. RESULTS: In three of the studied uterine cancers there was no positive staining of ER and PR; in one case there was a weak ER staining but PR staining was negative. In ER negative tumors the A level was significantly higher than in ER positive cancers (138.1 +/- 64.1 vs. 49.7 +/- 26.8 adducts per 10(9) nucleotides, respectively, p < 0.05). Highest A levels were found in two ER and PR negative G3 metastatic tumors. Finally, in all investigated cancers there was a strong, inverse correlation between ER content and A level (r = -0.67, p < 0.03). In addition, the correlation between PR level and A was of borderline significance (r = -0.6, p = 0.053). The TLC patterns of adducts in uterine tumors were found to be qualitatively similar, but not quantitatively, to those observed in normal human endometrium DNA. CONCLUSION: The data presented suggest that the hydrophobic DNA adducts could play a role in a sex-steroid hormone independence of human endometrial cancers. The highest accumulation of DNA adducts was recognized in neoplasms displaying the most malignant phenotype.