Solid pseudopapillary neoplasms of the pancreas: is there a pathologic basis for the observed gender differences in incidence?

BACKGROUND: The fact that solid pseudopapillary neoplasms of the pancreas (SPNP) occur predominantly in young women suggests that genetic and/or gender-specific factors may play a role in the pathogenesis. Therefore, SPNP derived from male patients may exhibit different molecular or clinicopathologic characteristics compared to SPNP derived from female patients. METHODS: We compared the immunohistologic staining patterns and presence of sex hormone receptors of SPNP obtained from 4 male and 11 female patients. In addition, we analyzed the clinical data from 285 (21 male and 264 female) previously reported patients with SPNP and our 15 patients. RESULTS: All 15 of the neoplasms were positive for progesterone, but negative for estrogen and androgen receptors. There were no immunohistologic differences between the genders. An analysis of all reported patients revealed no significant differences in patient age, size or location of the neoplasm, or malignancy rate. CONCLUSIONS: Although female patients with SPNP outnumbered male patients with SPNP, there were no gender-specific trends in expression of sex hormone receptor protein or clinicopathologic characteristics.     

Immunohistochemical detection of steroid receptors in a case of pulmonary lymphangioleiomyomatosis

Abnormal proliferation of smooth muscle cells in pulmonary lymphangioleiomyomatosis (LAM) is thought to be influenced by estrogen and progesterone. However, the results of previous studies using cytosolic methods to measure estrogen and progesterone receptor content in lung tissue from these patients have been inconsistent. We used immunohistochemical methods to study the tissue distribution of estrogen and progesterone receptors in LAM as well as in smooth muscle of several other organs, including histologically normal lung, colon, bladder, prostate, uterus, and uterine leiomyomas. Progesterone receptor was expressed strongly and estrogen receptor more weakly by the abnormal myoid cells of LAM. Hormone receptors were absent from all other constituents of lung tissue in our patient. These findings were similar to those in histologically normal myometrium and uterine leiomyomas. Although we found focal labeling of prostatic stromal cells with anti-progesterone receptor, no other smooth muscle tissue expressed either estrogen or progesterone receptor. We conclude that LAM is an abnormal proliferation of smooth muscle cells that express both estrogen and progesterone receptors.     

Estrogen and progesterone binding sites in renal cell carcinoma

Twenty-five renal cell carcinomas were assayed for estrogen and progesterone receptor levels. Estrogen specific binding was present in only 4 patients (16%) and progesterone specific binding in 7 patients (28%). In all cases these receptors were present in very low titers, less than 10 fm/mg. We believe that earlier reports citing significant estrogen and progesterone binding activity may reflect high levels of nonspecific protein binding.     

Estrogen and progesterone receptors in non small cell lung cancer patients.

The role of sex hormones in the pathogenesis of lung cancer is still unknown. There are conflicting results regarding immunohistochemical detection of the estrogen and progesterone receptors expression in non small cell lung cancer. To clarify these discrepancies 32 samples of lung carcinoma tissues obtained by lobectomy or pneumonectomy were studied. Two monoclonal antibodies (6F11 and ID5) for estrogen receptor detection and one (1A6) for progesterone receptor detection were used. Eighteen adenocarcinoma and 14 squamous cell carcinoma cases were investigated. There were 11 women and 7 men with adenocarcinoma and 4 women and 10 men with squamous cell carcinoma. Weak (+1) nuclear estrogen hormone receptor expression was detected in only one specimen of a woman with adenocarcinoma and in one specimen of a man with squamous cancer. None of the 32 blocks of paraffin embedded specimens expressed progesterone receptor. The positive estrogen and progesterone receptors expression in cancer tissue is an important argument against the pulmonary origin of the unknown primary tumor.     

Estrogen and progesterone receptors in meningiomas

Estradiol and progesterone receptors were studied in 14 patients with meningiomas. Estrogen receptors were detected by specific monoclonal antibodies, whereas progesterone receptors were assayed by the dextran-coated charcoal method. In 9 cases the estrogen receptors were also investigated in cultured tumor cells. Positive estrogen and progesterone receptors were found in 86% of patients. The results have been compared with 11 published series of sex steroid assays in meningiomas. The different rate of positive results in most series can be explained by preoperative glucocorticoid therapy. There is no correlation between the estrogen and progesterone receptor activity, the sex and age of the patients, and the location and histological features of the meningioma. The authors suggest that assays of antiestrogen and antiprogestin drugs in cultured cells can indicate whether this estrogen and progesterone receptor activity may be of therapeutic use.     

Human breast carcinoma (MCF-7) serially transplanted into nude mice

The tumor cells (0.5 ml, 1×10⁷) of MCF-7 line were inoculated into the subcutaneous tissue or intraperitoneum of female BALB/c nude mice. Primarily tansplanted mice were treated with 17β-estradiol dipropionate (E₂) in a dose of 5 mg/kg and 17α-hydroxy progesterone caproate (Pg) in a dose of 250 mg/kg once a week. After the transferable strain was established, tumors were transplanted into female and male mice treated with E₂, Pg, and E₂+Pg. The tumors treated with E₂ or E₂+Pg grew exponentially while tumors in the other group regressed. Pg was assumed to play some role in the growth of MCF-7, in the presence of estrogen. Although cytosol estrogen receptors (ERc), nuclear estrogen receptors (ERn), and progesterone receptors (PgR) were detected by dextran coatedcharcoal method and exchange assay in the growing tumors, ERn and PgR of regressing tumors was usually negative. This MCF-7 strain in nude mice may be a promising animal model for studying chemo-hormone therapy for human breast carcinomas.     

Q-Switched Ruby Laser Treatment for Postsclerotherapy Hyperpigmentation

BACKGROUND: One of the most common adverse sequelae of sclerotherapy is cutaneous hyperpigmentation. OBJECTIVE: We used the Q-switched ruby laser to treat postsclerotherapy hyperpigmentation. METHODS: Eight patients developed pigmentation lasting more than 1 year (1-2 years on average) after sclerotherapy treatment for reticular and telangiectatic veins in the legs ranging in size from 0.2 to 4 mm in diameter. All patients were treated with a Q-switched ruby laser at 694 nm, 4 mm beam size, and fluence range of 5.6-10.5 J/cm2. RESULTS: Ninety-two percent of lesions lightened after treatment. There was significant (75-100%) resolution of hyperpigmentation in 58% of treated areas, 25% improvement in 33% of treated areas, and no improvement in the remaining areas. CONCLUSION: Our impression is that given a choice of lasers, the Q-switched ruby laser provides the greatest efficacy for treating postsclerotherapy hyperpigmentation.     

男性胆囊结石患者性激素变化及其受体状态的研究

采用放射免疫和免疫组化的方法检测３０例男性胆囊结石患者血清雌二醇（ｅｓｔｒａｄｉｏｌ,Ｅ２）、睾酮（ｔｅｓｔｏｓｔｅｒｏｎｅ,Ｔ）、孕酮（ｐｒｏｇｅｓｔｅｒｏｎｅ,Ｐ）的含量以及胆囊组织雌激素受体（ｅｓｔｒｏｇｅｎ ｒｅｃｅｐｔｏｒ,ＥＲ）和孕激素受体（ｐｒｏｇｅｓｔｅｒｏｎｅ ｒｅｃｅｐｔｏｒ,ＰＲ）的表达,并与１８例年龄相仿的非结石性胆囊病是进行了对照组分析。实验结果表明,男性胆囊结石患因清Ｐ     

Type II estrogen binding sites (EBS) in intracranial tumors

Four meningiomas and six neuroepithelial tumors were assayed for the presence of estrogen receptors (ER), type II estrogen binding sites (EBS) and progesterone receptors (PgR). ER were detected in 7 out of 10 cases with levels ranging between 2.5 and 20.7 fmoles/mg of cytosolic protein. On the contrary, PgR were found in all samples (10 cases) and their levels ranged between 8.8 and 130.6 fmoles/mg of cytosolic protein. All tumor samples expressed appreciable amounts of type II EBS ranging between 452 and 2320 fmoles/mg of protein. Although the precise functional role of type II EBS is still unknown, their presence may reflect an hormonal sensitivity of these tumors.     

Estrogen and progesterone receptor-negative T11 vertebral hemangioma presenting as a postpartum compression fracture: case report and management

OBJECTIVE AND IMPORTANCE: Pregnancy-related vertebral hemangioma compressive myelopathy is a rare occurrence that tends to arise in the upper thoracic and lower cervical spine, peaks during the third trimester, and remits after parturition. Whether corticosteroid receptors play a role in the pathogenesis of these lesions is unknown. Most of these lesions have been managed with posterior decompression. CLINICAL PRESENTATION: A 29-year-old woman presented with acute-onset lower-extremity weakness and sensory loss immediately after parturition. INTERVENTION: We used a retropleural approach for anterior decompression and fusion, followed by radiation therapy. Immunohistochemical analysis of estrogen and progesterone receptor expression was performed. CONCLUSION: We report an unusual case of lower thoracic postpartum vertebral hemangioma compressive myelopathy caused by a parturition-related compression fracture. Results of tests for corticosteroid receptors were negative, which implicated a hemodynamic rather than hormonal cause for disease progression.     

Correlation of estrogen, progesterone, and androgen receptors in breast cancer

Breast cancer was induced in female Holtzman rats by intragastric administration of 7,12-dimethylbenz[a]antracene (DMBA). At tumor maturity, biopsies of viable tissue were obtained, frozen, and then assayed for estrogen, progesterone, and androgen receptor content. By simple linear regression analysis, progesterone receptor levels significantly correlated with both estrogen and androgen receptor levels, whereas estrogen and androgen receptor levels did not correlate with each other. Multiple regression analyses further substantiated the predictive value of the progesterone receptor for the other two hormone receptors. Knowledge of breast tumor androgen receptor levels may further enhance the value of the estrogen receptor and progesterone receptor in hormonal responsiveness. Further, the progesterone receptor may be the most sensitive of the steroid hormone receptors for selecting patients likely to respond to hormonal therapy.     

Progesterone receptors regulate gallbladder motility

The increased incidence of gallstones in multiparous women may be related to hormonal effects on the gallbladder and its contractility. The occurrence of estrogen and progesterone receptors were studied in the gallbladders of three groups of female guinea pigs (normals, oophorectomized, and oophorectomized treated with estrogen + progesterone for 14 days). Gallbladder contractile response in vivo to cholecystokinin (CCK) was related to the presence of these receptors. The gallbladders from normal females showed low progesterone and estrogen binding activity (4.9 +/- 2.0 and 2.4 +/- 0.8 fmoles/mg cytosol protein). Oophorectomized females had no detectable progesterone or estrogen receptors, but after treating oophorectomized females for 14 days with estrogen + progesterone, gallbladder concentrations of progesterone receptors increased significantly to 14.7 +/- 5.9 fmoles/mg and estrogen binding activity was minimally detectable at 1.4 +/- 0.8 fmoles/mg. The gallbladder contractile response to CCK was inversely related to the concentration of progesterone receptors in the gallbladder wall. These data suggest that the gallbladder contains progesterone receptors which are susceptible to circulating hormonal conditions and which have a regulatory effect on gallbladder contractility.     

Estrogen and progesterone binding by acoustic neuroma tissue

Tissue samples from 37 acoustic neuromas were assayed for estrogen and progesterone hormone receptor binding by radioimmunoassay using a dextran-coated charcoal method and Scatchard plot analysis. Twenty-one of the samples were from men, and 16 of the samples were from women. Seven of 37 samples (19%) were positive for estrogen receptor and six of 36 samples (17%) were positive for progesterone receptor. Three of 37 samples (8%) were positive for both receptors. There was no correlation of estrogen receptor positivity with the sex of the patient. These results indicate that estrogen or progesterone receptor binding activity or both are present in a small subset of acoustic tumors. Evidence is lacking, however, that binding of estrogen to the receptor results in growth changes in the tumor. The empirical use of antiestrogen treatment in acoustic neuroma does not appear to be justified at the present time.     

Hormonal dependency of cerebral meningiomas. Part 1: Female sex steroid receptors and their significance as specific markers for adjuvant medical therapy

Female sex steroid receptors were examined in 50 human cerebral meningiomas. For estrogen receptors, high-affinity binding sites (dissociation constant (Kd): 0.05 to 0.2 nM) were found in the cytosolic fraction with a capacity of less than 4 fmol/mg protein in 10 meningiomas using a dextran-coated charcoal (DCC) assay. In the same cytosolic fraction, the solid-phase enzyme immunoassay revealed only one cytosol with a positive colorimetric reaction equal to 5 fmol/mg protein. However, in the nuclear compartment, none of the tumors stained positively for estrogen receptors with immunohistochemical techniques. In addition, the most convincing evidence for the absence of estrogen receptors was obtained by in situ hybridization using an oligonucleotide probe complementary to a fraction of the human receptor messenger ribonucleic acid (mRNA). In none of the 50 meningiomas was the expression of estrogen mRNA coding for the estrogen receptor detected. For progesterone receptors, high-affinity binding sites (Kd: 0.3 to 2.6 nM) were found in 49 of the 50 tumors using a DCC assay. In the same cytosols, solid-phase enzyme immunoassay revealed that each tumor was positive for progesterone receptors. However, in the nuclear compartment, only five tumors had partially positive staining for progesterone receptors with immunohistochemical techniques. Within the confines of this study, it is concluded that: 1) the estrogen receptor is generally absent in meningioma tissue, and 2) the progesterone receptor is mainly absent in the nuclear compartment, leading to the conclusion that the cytosolic progesterone receptor may be an inactive form. This study suggests that female sex steroid receptors are not primarily involved in the proliferative rate of cerebral meningiomas and that they are of no current significance as markers for adjuvant medical therapy of most meningiomas.     

There are no estrogen and progesterone receptors in cerebral cavernomas: A preliminary immunohistochemical study

Background

Literature consistently mentions that pregnancy and hormonal therapy probably increase the bleeding rate and seizure expression of cerebral cavernomas. Either increased hormonal activity or embryogenesis related abundant expression of some growth factors such as VEGF, bFGF, and placental growth factor during pregnancy were proposed to initiate angiogenic process and vascular proliferation in cavernomas, thereby increasing their bleeding rate and seizure expression.

Methods

To reveal whether estrogen and/or progesterone have direct effect on cerebral cavernomas, their receptor expressions were studied immunohistochemically in recently excised 12 cerebral cavernomas.

Results

Study showed no expression of either estrogen or progesterone receptors in cerebral cavernomas even the staining worked well in positive control tissues of infiltrative ductal carcinoma.

Conclusions

Aggressive behavior of cerebral cavernomas during pregnancy is a commonly proven observation and attributed to some hormonal effects. However, this effect seems not related to effect of estrogen or progesterone on cavernoma tissue via receptor binding.     

Estrogen receptor in human benign prostatic hyperplasia

Estrogens have been proposed as a major etiological factor in the pathogenesis of benign prostatic hyperplasia in man. The presence of estrogen receptor in benign prostatic hyperplasia would support this concept. Using the receptor stabilizer, sodium molybdate, and a hydroxylapatite assay we assayed human benign prostatic hyperplasia for the presence of cytosolic estrogen receptor. For comparison, we assayed estrogen receptor in cytosols of prostatic cancer and normal tissue, and we also measured androgen receptor and progesterone receptor concentrations in the 3 tissue types. Estrogen receptor was present in 8 of 15 benign prostatic hyperplasia specimens at a mean concentration of 9.2 fmol./mg. protein for the estrogen-receptor-positive samples. Sucrose gradient analysis of the estrogen receptor of benign prostatic hyperplasia revealed that it sedimented in the region of 8S, and steroid specificity studies confirmed that the binding to estrogen receptor was estrogen-specific. Estrogen receptor was also found in normal (3 of 3) and malignant (4 of 6) tissues, and all tissues were positive for androgen receptor. The presence of estrogen receptor in human benign prostatic hyperplasia supports the proposal that circulating estrogens may have a role in the pathogenesis of this disorder.     

Cutaneous Hyperpigmentation Following Venous Sclerotherapy Treated with Deferoxamine Mesylate

BACKGROUND: Cutaneous hyperpigmentation after venous sclerotherapy is an adverse sequelae of difficult management. OBJECTIVE: To evaluate the degree of depigmentation with the use of deferoxamine mesylate (DM) in patients with postsclerotherapy hyperpigmentation treated with polydocanol (POL) for telangiectasias and reticular veins (0.2-5 mm diameter) and varicose veins (5-8 mm diameter). METHODS: The experimental group of 36 female patients (mean age 37 years) was divided in two groups. Group I consisted of 30 patients who were treated with POL at 0.25-0.50% concentration for telangiectasias and reticular veins. Group II consisted of six patients with prolonged postsclerotherapy hyperpigmentation (more than 6 months after treatment) in varicose veins that had been treated with POL at 1.5% concentration each week. Groups I and II were injected with DM 500 mg subcutaneously once a week until 81-100% depigmentation was reached. In group I, DM was injected at the time of sclerotherapy. These groups were compared to their respective control groups with similar conditions but allowing spontaneous depigmentation without DM. Evaluation was undertaken clinically and photographically, and the number of days required to reach the desired depigmentation of 81-100% was determined. RESULTS: When DM was used, depigmentation of 81-100% was observed in group I at 27 days, and for group II in 46 days. In each control group, similar depigmentation was seen at 150 +/- 19 and 255 +/- 11 days, respectively. Comparing results, there was a reduction in the time to depigmentation of 82% for each group (P <.0001). CONCLUSION: The weekly subcutaneous administration of DM 500 mg reduces the time to depigmentation by 82% in patients with postsclerotherapy cutaneous hyperpigmentation treated for telangiectasias and reticular veins and prolonged postsclerotherapy hyperpigmentation in varicose veins. In this study we could not explain why such variability exists in the length of time to spontaneous depigmentation.     

Evidence of progesterone receptors in the mucosa of the urinary bladder.

OBJECTIVE: To investigate whether progesterone receptors are present in the mucosa of the urinary bladder of continent premenopausal women compared with continent postmenopausal women. MATERIALS AND METHODS: Fifty-seven biopsies from the mucosa of the trigone and lateral wall of the urinary bladder were examined by the avidin-biotin-peroxidase immunohistochemical technique for the presence of estrogen and progesterone receptors. The specimens were obtained at cystoscopy performed to investigate hematuria in 42 patients and neoplasia in 15. The study group (n = 29) comprised non-pregnant premenopausal women in the luteal phase of their menstrual cycle and the control group (n = 28) comprised postmenopausal women. None of the subjects had urinary incontinence or was taking medication with hormones. In no case did the primary lesion involve the specimen used for laboratory analysis. RESULTS: There was positive immunostaining with estrogen in 28 patients of the study group (96.5%) and 4 (14.4%) in the control group (p<0.0001). The 28 samples of the study group also showed positive immunostaining for progesterone receptors. There was positive immunostaining with progesterone in 18 samples (64.3%) of the control group (p<0.01). Fourteen samples (50%) of the control group thus showed positive immunostaining for progesterone but no evidence of positive immunostaining with estrogen. Immunostaining for estrogen and progesterone receptors was similar in trigonal and lateral wall samples. CONCLUSION: In continent pre- and post-menopausal women, a direct progestogenic effect on the mucosa of the urinary bladder seems likely in addition to estrogen.     

Clinical Characteristics of 500 Consecutive Patients Presenting for Laser Removal of Lower Extremity Spider Veins

BACKGROUND: Laser treatment for removal of lower extremity spider veins is emerging as a modality of choice in patients with small spider veins, those who have previously undergone sclerotherapy or vein stripping, and those refusing sclerotherapy. OBJECTIVE: To determine clinical characteristics of patients presenting for laser treatment of leg veins. METHODS: The clinical characteristics of 500 patients presenting for laser treatment of spider veins were evaluated to investigate characteristics leading to their development, and to characterize the type of patients presenting for laser treatment. RESULTS: Patients presenting for treatment range widely in age and have had spider veins for an average of 14 years. Both pregnancy and previous sclerotherapy were factors that contributed to the development or exacerbation of spider veins. CONCLUSION: As laser treatment of spider veins improves, this modality will play an increasing role in the management of lower extremity telangiectasias.     

A Reappraisal of Progesterone Action in the Mammary Gland

The ovarian hormones estrogen and progesterone and their respective receptors are essential for maintenance of postnatal developmental plasticity of the mammary gland and play a key role in mammary tumorigenesis. Mouse models in which expression of the progesterone receptors was genetically ablated have recently become available. Studies of these models have demonstrated that progesterone is specifically required for pregnancy associated ductal proliferation and lobuloalveolar differentiation of the mammary epithelium, but not for immediate postpubertal ductal morphogenesis. Use of these mice in combination with mammary gland transplantation indicates that developmental regulation by progesterone appears to occur through a paracrine mechanism in which progesterone receptor (PR)³ positive cells represent a subset of non-proliferating epithelial cells that are capable of directing proliferation and/or differentiation of neighboring receptor negative cells. The hierarchical organization of these receptors in the epithelium and their segregation from proliferating cells is a conserved feature in rodent and human mammary tissue. The identification of paracrine mediators of the progesterone response is now an imminent goal as is the delineation of the individual contributions of the two PR isoforms using similar approaches.