Estrogen and progesterone receptors in primary cutaneous melanoma

Using a variety of techniques, estrogen and progesterone receptors have previously been identified in variable percentages of malignant melanomas. We examined 10 primary superficial spreading melanomas (SSM) with a fluorescent hormone-binding technique for estrogen and progesterone cytoplasmic receptors. Of these 6 SSM were markedly positive for estrogen and progesterone binding. Patients with dysplastic nevus syndrome (DNS) or a family history of DNS were markedly positive for estrogen and progesterone binding. A single patient with lentigo maligna and another patient with lentigo maligna melanoma were negative for estrogen and progesterone binding. None of the 21 control intradermal nevi examined for estrogen and progesterone binding exhibited marked positivity.     

Improved method for assay of estradiol and progesterone receptors with special reference to breast cancer

Isoelectric focusing of estradiol receptor (ER) and multiple point dextran-coated charcoal (DCC) technique for progesterone receptor (PgR) were adapted for assay of both receptors in the same cytosol sample. Technical improvements and increased recovery of receptors were achieved. 1.0 fmol/ml cytosol of ER may be detected; sensitivity of PgR was 5-10 fmol/ml cytosol. Quantitation of ER was made in 414 (95%) out of 434 consecutive breast cancers. Inclusion of isoelectric focusing records showing only qualitative indication for presence of ER resulted in 98% ER containing tumours, supporting the aspect that strictly ER negative tumours are a rarity. Implications for therapy in disseminated disease are discussed.     

Estrogen and progesterone receptors in breast cancer: correlation with clinical and pathological features and with prognosis.

Estrogen and progesterone receptor status was reviewed in 405 patients from prior adjuvant breast cancer trials at the University of Verona. Only 233 patients were actually examined with respect to hormone status and outcome. No relationship between hormone receptor status and most of the commonly followed prognostic signs, i.e. tumor size, nodal status, and age, was found. Overall survival was correlated with hormone receptor positivity for patients with more than 4 positive axillary nodes. Disease-free survival was correlated only with PgR positivity, in premenopausal and in T1 groups.     

Estrogen and progesterone receptors in ovarian cancer

To determine whether steroid hormone receptor expression is clinically relevant in ovarian cancer, cytoplasmic and nuclear estrogen (ER) and progesterone (PR) receptor levels have been measured and their concentration calculated by Scatchard analysis. Of 89 samples from patients with non-pretreated epithelial ovarian cancer, 33% were ER-positive, PR-positive (ER+PR+) and 40% ER-negative, PR-negative (ER-PR-); 20% were ER+PR-, and 7% ER-PR+. There was no correlation between receptor status and patient age, menopausal status, or tumor grade, although serous tumors were more likely to be ER+. The incidence of PR+ tumors was highest in early disease and decreased with increasing International Federation of Gynecology and Obstetrics (FIGO) stage. Survival of patients with advanced disease (FIGO Stages IIC, III, or IV) was significantly prolonged by optimal initial cytoreductive surgery (P = 0.002), platinum therapy (P = 0.003), and tumor expression of PR (P = 0.009). On multivariate analysis, PR positivity was still associated with improved survival, although this did not retain statistical significance (P = 0.09).     

Estrogen and progesterone receptors in gastric cancer

Cancerous tissue from 86 patients with primary gastric cancer were examined for the presence of receptors for estrogen (ER) and progesterone (PgR). ER and PgR were present in 8 (15.4%) and 5 (9.6%), respectively, of 52 male patients, 9 (26.6%) and 7 (20.6%), respectively, of 34 female patients, a total of 17 (19.8%) and 12 (14.0%), respectively. One male patient (1.9%) and 4 female patients (11.8%) had both ER and PgR, and 40 male (76.9%) and 22 female patients (64.7%) showed no ER or PgR. The binding activity ranged from 6 to 200 fmol/mg protein for estradiol and from 5 to 58 fmol/mg protein for progesterone. ER- and/or PgR-positive cases were characterized grossly as Borrmann type 4, and microscopically as diffuse type with scirrhous growth pattern. The presence of ER and/or PgR in some gastric cancers indicates the possibility that sex hormonal factors are involved in these tumors.     

Estrogen and progesterone receptors in bronchogenic carcinoma

Although the lung is not usually considered a major target organ of sex hormones, epidemiological observations, studies of pulmonary neoplasms in laboratory animals, and investigations of carcinomas derived from other "nontarget" organs suggest that sex hormones may have a role in the pathogenesis of bronchogenic carcinoma. To confirm that estrogen (ER) and progesterone receptors are present in human lung cancers, 19 resected lung cancers were examined for receptors using a prelabeled sucrose gradient method. Three squamous cell carcinomas were positive for ER (greater than 6.9 fmol/mg cytosol protein). Three squamous cell carcinomas, two adenocarcinomas, and one small cell carcinoma were positive for progesterone receptors (greater than 6.9 fmol/mg cytosol protein). One tumor, a squamous cell carcinoma arising in a woman who smoked, had an ER level of 301 fmol/mg, a highly positive level even for breast cancers. These observations may provide a basis for adjuvant hormonal therapy in selected lung cancer patients.     

Estrogen and progesterone receptors in the normal female breast

We have studied estrogen receptor (ER) and progesterone receptor (PR) in normal breast by immunocytochemistry using tissue biopsies and fine needle aspirates (FNA) and, in the case of ER, by enzyme immunoassay. For ER we found a high degree of reproducibility for biopsies taken from the upper outer quadrant: FNA, r = 0.56 (P less than 0.002); tissue section immunocytochemistry, r = 0.89 (P less than 0.0001); and enzyme immunoassay, r = 0.76 (P less than 0.0001). For PR, FNA (r = 0.56, P less than 0.002) and tissue section (r = 0.97, P less than 0.0001) were also found to be reproducible techniques. Using enzyme immunoassay, we were able to measure ER accurately in normal breast tissue. In 59 samples we found a range of 0-37 fmol/mg cytosol protein (mean, 4 fmol/mg). In an age-matched group of 126 women with breast cancer, we found a significantly higher ER [range, 0-139 fmol/mg; mean, 37 fmol/mg (P less than 0.001)]. We then analyzed the ER and PR content of FNAs obtained from the upper outer quadrant of the normal breast in 143 normal women. We found that in only 23 of 143 samples (16%) were greater than or equal to 50% epithelial cells stained. There was a relationship between ER and PR (P = 0.03) and a higher ER content in European women than in non-European women (P less than 0.03). The PR content was related to high body mass index (P less than 0.02) and family history of breast cancer (P = 0.04). Samples tended to be more frequently ER positive by FNA if taken in the follicular phase of the menstrual cycle. We conclude that, although the levels of ER and PR are low in normal breast, they can be accurately measured. There is significant variation of ER and PR with several clinical parameters.     

Prognosis for localized cutaneous melanoma treated with wide excision only, with special reference to development of regional node metastases

A consecutive series of 564 patients with localized (Stage I) melanoma treated by wide excision only were followed for at least 5 years. The median tumor thickness was 1.50 mm, and 30% were ulcerated. The female/male ratio was 54/46. The overall survival rates were 80% at 5 years and 73% at 10 years. The survival rates were statistically significantly better for females, even when tumor thickness and ulceration were taken into consideration. Twenty percent developed regional node metastases after an average remission period of 13 months. The actuarial survival rates after node dissection were 32% at 5 years and 27% at 10 years. A subgroup with an exceptionally poor prognosis and a high rate of regional node dissemination was looked for. Only 26% of the intermediate thickness group (1.50-3.99 mm, Breslow) developed nodal metastasis, whereas patients with thick lesions (greater than 4 mm) had a metastasis rate of 43%. Patients with thick lesions may therefore benefit more from elective node dissection than patients with lesions of intermediate thickness. Patient characteristics, e.g., sex and tumor characteristics (ulceration), may prove to be of importance in a prospective trial on elective node dissection.     

Estrogen and progesterone receptors as prognostic factors in breast cancer

The relation between estrogen receptors (ER) and/or progesterone receptors (PgR) and some clinical factors such as tumor size, axillary node involvement, histological tumor grade, and disease-free interval (DFI) in 500 patients with operable (TNM stage I-III) breast cancer was studied. ER-positive (ER+) tumors were commoner in older patients, whereas PgR-positive (PgR+) tumors were similarly distributed within the age groups. The concentration of ER+ protein also increased with age in contrast to PgR+ protein concentration. However, receptor status was not associated with menopausal status independently of age. Axillary node involvement influenced neither ER nor PgR status, but there was a statistically significant relation between tumor size and positivity of ER or PgR. There was no association between histologic tumor grade and either steroid receptor phenotype. DFI was longer in patients with ER+ than those with ER- tumors, independently of axillary nodal status. The positivity of PgR in patients with ER+ tumors contributed to an even longer DFI, suggesting that the combination of ER/PgR is a better indicator of DFI than ER or PgR alone.     

Estrogen receptors,progesterone receptors,and cell proliferation in human breast cancer

Summary The breast is a target organ for estrogens and progesterone. These hormones control several functions of the normal and abnormal mammary epithelium including cell proliferation. Most of the actions of estrogens and progesterone are mediated via specific steroid receptors, and one would expect that proliferating cells should contain estrogen receptors (ER) and/or progesterone receptors (PR). However, the correlation between receptor expression and cell proliferation is still controversial. In the present study we have examined 29 human breast cancer samples; in 17 of them we evaluated the simultaneous ER and PR localization with that of proliferating cell nuclear antigen (PCNA) and silver-stained nucleolar organizer regions (AgNORs) in a cell-by-cell study. We found that in almost 50% of the tumor biopsies examined, the cells expressing ER were significantly associated with elevated cell proliferation. In another group (38%) there were not significant differences between ER expression and cell proliferation. In only one of the samples (6%) the cells expressing ER showed lower cell proliferation. The study also revealed that in 44% of the tumors the PR expressing cells were associated with elevated cell proliferation. In a second group the PR expression was not significantly associated with cell proliferation (33% of the cases). Finally, in 22% of the samples the cells carrying PR showed lower cell proliferation. We also detected lower ER immunoreactivity in 30% of the breast cancer biopsies with one of the monoclonal antibodies against ER (antibody 1D5 directed against the A/B domain). This group of tumors was PR-negative (or very weakly positive) and had high proliferation. The presence of tumors with abnormal ER proteins and displaying ER/PR significantly associated with elevated cell proliferation could have implications in human breast cancer treatment.     

Estrogen and progesterone receptors in cervical human papillomavirus related lesions.

According to recent studies showing that human papillomavirus (HPV) infections can be influenced by sex steroid hormones, we performed estrogen (ER) and progesterone (PgR) receptor assays in fresh frozen biopsies of genital-HPV-related lesions. Seventy-three women with normal cervix, condyloma, low- and high-grade CIN and squamous carcinoma were evaluated in comparison with 15 persons with vulvar and 9 with penile papillomavirus-associated lesions. HPV genotypes were determined by dot-blot hybridization. Non-cervical lesions did not express HR. Condyloma on squamous metaplasia of the cervix and high-grade CIN expressed high levels of HR, particularly PgR (mean 4,086 and 4,518 fmoles/g tissue, respectively). Cervical squamous carcinoma expressed very low concentrations of PgR in a limited number of cases. High levels of PgR were correlated with high-grade CIN (p less than 0.05), HPV16-18-associated lesions (p less than 0.01) and ER were correlated to HPV6-11-related lesions (p less than 0.01). The levels were independent of age, cycle stage and oral contraception. Morphological localization of PgR, using an immunocytochemical method using a monoclonal antibody (MAb) (PR-ICA), showed intense homogeneous staining in the nuclei of the stromal fibroblasts underlying dysplastic epithelium and condyloma on squamous metaplasia. These results suggest that, under in vivo conditions, sex steroid hormones, particularly progesterone, may act indirectly on HPV-infected epithelial cells and be implicated as co-factors in HPV-related cervical neoplasia. They could explain the relative predisposition to malignant transformation of the cervix as compared with vulvar and penile mucosa.     

Estrogen and progesterone receptors in breast carcinoma and in nonmalignant breast tissue

Since 1983 we have studied the relationship, in the same patient, between receptor status in breast carcinoma and in nonmalignant breast tissue. Fifty patients have been evaluated to date. The total unoccupied cytosol estrogen and progesterone receptors were determined by a dextran-coated charcoal method. In nonmalignant breast tissue we found a measurable receptor concentration above the sensitivity of the method in 62% of cases for estrogen receptors and in 44% of cases for progesterone receptors. No relationships were found between the receptor level of each tumor and that of the corresponding benign tissue. The data suggest that the levels of the receptors in the tumor and in the nonmalignant tissue are totally independent.     

卵巢肿瘤雌孕激素受体、雌二醇、孕酮测定及其临床意义

本文测定了５０例卵巢肿瘤患者手术前后血浆雌二醇（Ｅ＿２）和孕酮（Ｐ）水平。并用葡聚糖─活性碳吸附法（ＤＣＣ）测定了５０例卵巢肿瘤和６例正常卵巢组织胞浆雌（ＥＲｃ）、孕（ＰＲｃ）激素受体和胞核雌（ＥＲｎ）、孕（ＰＲｎ）激素受体。结果表明卵巢恶性肿瘤具有高的ＥＲｃ、ＰＲｃ和低的ＥＲｎ、ＰＲｎ、Ｅ＿２和Ｐ。提示对卵巢肿瘤患者常规进行Ｅ＿２、Ｐ测定，可作为鉴别卵巢恶性肿瘤的参考。对受体含量高的卵巢恶性肿瘤，有用内分泌治疗的可能和推测较好预后。     

Cytofluorometric analysis of metastases from lung adenocarcinoma with special reference to the difference between hematogenous and lymphatic metastases

Metastatic tumors in the brain, liver, and regional lymph nodes (20 cases each) from patients with adenocarcinoma of the lung were examined by cytofluorometric analysis, and compared with the respective primary lung tumors. The nuclear DNA content of tumor cells was significantly increased in metastatic tumors in the brain and liver compared with the primary (P less than 0.01). However, the DNA content of metastatic tumors in regional lymph nodes was almost identical to that of the primary tumor in many instances. From the viewpoint of the nuclear DNA content of lung adenocarcinoma, blood-borne tumor cells in the brain and liver were considered likely to constitute a discrete tumor cell subpopulation, i.e., probably a more malignant one, different from the major subpopulation in the primary tumor, whereas lymphatic metastases in regional lymph nodes were similar to the primary. The subpopulation with an increased DNA content in hematogenous metastases were thought to have originated from a minor subpopulation in the primary tumor or to have developed at the metastatic site.     

Long-term survival in malignant melanoma with special reference to age and sex as prognostic factors

A total of 12,353 (97.5%) of all patients with a first malignant melanoma newly diagnosed in Sweden during the period 1960-82 were subjected to a complete computerized follow-up with respect to survival through December 31, 1982. Calculation of relative survival rates (RSs) revealed a consistently more favorable course in women than in men, the 5-year RSs being 80.8 and 68.0% and the 10-year RSs being 75.0 and 61.8%, respectively. Prolonged follow-up and analyses of annual excess mortality showed, in addition, that men surviving about 10 years constituted an apparently cured fraction, whereas among women there was an excess mortality throughout the observation period. The prognosis was increasingly more favorable at younger ages in males, whereas no regular age trend emerged in the female group of patients. A multivariate analysis indicated that the findings were not confounded by temporal trends in RSs or by differences in tumor location between the groups compared and also that the relative hazard was significantly higher for men than for women only during the first 8 years after diagnosis.     

Southern travelling habits with special reference to tumour site in Swedish melanoma patients.

Southern travelling habits were recorded for 127 melanoma patients from southern parts of Sweden (the 56th latitude), 55 thyroid cancer patients, 100 non-Hodgkin's patients and 794 healthy controls from the same region. Melanoma patients were found to travel significantly more often south of the 45th latitude, as compared with patients with non-Hodgkin's lymphoma or thyroid carcinoma (RR = 2.2 for a difference of + 10 trips), and with the healthy controls (RR = 1.4 for a difference of + 10 trips). Considering men and women separately, the difference was significant only for men. Patients with melanoma had a higher educational level than the tumour controls and the healthy controls (p < 0.001 and p < 0.001 respectively). There was a significant correlation between high travelling frequency and high education. An increased risk related to southern travelling was present for patients with melanoma on the extremities and head and neck, as well as for patients with truncal melanoma. These findings support the concept that acute exposure to sunburn may be a risk factor for malignant melanoma.     

Estrogen and progesterone receptors in malignant mixed mesodermal tumors of the ovary

Malignant mixed mesodermal tumors of the ovary occur in less than 1% of cases of ovarian cancer. They have a dismal prognosis and the most effective type of therapy is still not known. All cases of malignant mixed mesodermal tumor of the ovary between Jaunary 1, 1985 and May 1, 1994 operated on by the gynecologic oncology service are the subject of this report. Data were obtained from the hospital and office records of the patients. Nine patients who had their primary surgery by the gynecologic oncology service were found to have the diagnosis of malignant mixed mesodermal tumor of the ovary. Homologous tumors were found in five patients and heterologous tumors in four. Homologous tumors (mean survival 15.2 months) showed a better survival than heterologous tumors (mean survival 6.5 months; P = 0.001). An elevated estrogen receptor status was shown to correspond to longer survival (p < 0.0001). Six specimens were considered to be estrogen receptor positive and three were receptor negative. The mean survival in those patients who had a positive estrogen receptor status, 13.7 months, with a median of 7.5 months was significantly higher than those who were not positive, 6.7 months (P = 0.019) with a median of 6.25 months. All specimens were progesterone receptor negative. Malignant mixed mesodermal tumors of the ovary have a dismal prognosis, no effective therapy, and controversial prognostic indicators. Increasing estrogen receptor status appeared to correlate with longer mean survival. Larger, multi-institutional studies need to be done to determine the overall significance of these findings.     

Estrogen and progesterone receptors in breast cancer: relationships to tumour histopathology and survival of patients

Estrogen receptor (ER) and progesterone receptor (PR) concentrations were measured in the tumours of 399 cases of primary breast carcinoma. Histological type and histological grading was also analysed. The correlation between survival and histological grading was observed and found to be of high significance statistically. Longer survival of patients with ER- and/or PR-positive tumours was also observed, but the ER and PR prognostic value did not reach the same magnitude as histological alone. The prognostic accuracy in breast cancer, when histological grading, ER and PR were used together, failed to reach statistically significant values. A lower proportion of ER- and PR-positive tumours were found in histological grade III. The majority of the tumours belonging to specific histological variants of carcinoma were ER- and/or PR-positive. Relationships between ER, PR, menopausal status, and age were also noted. It was apparent that the prognostic value of PR concentrations in the tumour was more relevant than that of ER alone.