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J Spona

Publications and source records attributed to J Spona.

At least 37 records · Page 2Linked to original sources

Immunohistochemical and biochemical measurement of estrogen and progesterone receptors in primary breast cancer. Correlation of histopathology and prognostic factors.

OBJECTIVE: The authors investigated correlations of estrogen-receptor and progesterone-receptor with conventional risk factors as well as histopathology in patients with primary breast cancer. SUMMARY BACKGROUND DATA: Immunohistochemically determined hormone receptors have gained importance as prognosticators in primary breast cancer, but their definitive role has not yet been evaluated. METHODS: Tumor samples from 299 patients were examined for estrogen and progesterone receptors by biochemical and immunohistochemical assay. Correlations with established risk factors (tumor size, lymph node status, menopausal status, grading including subfactors) and histopathology were analyzed. RESULTS: The estrogen receptor, determined by immunohistochemical method revealed positivity in 80.6% of patients; biochemical measurement yielded 76.2% positive results. The progesterone receptor measured by immunohistochemistry yielded 61.3% positivity versus 55.8% detected by biochemical analysis. Invasive lobular, tubular, and ductal invasive carcinoma with prominent stroma content ("scirrhous carcinoma") rather than ductal invasive carcinoma was more frequently estrogen-receptor positive with immunohistochemistry than with biochemical assay. For progesterone receptor, the same pattern of positivity was seen with immunohistochemical assay. With progesterone receptor determined biochemically, "scirrhous" and lobular carcinoma showed positive results in a lower proportion than invasive ductal and tubular carcinoma. Significant correlations were observed between the estrogen-receptor status, the histologic grade of malignancy, nuclear polymorphism, and the rate of mitosis with both methods (p < 0.001 respectively). Different correlations were found between tumor size, menopausal status and estrogen receptor status with both assays respectively. For the progesterone receptor status, immunohistochemistry yielded significant correlations with the histologic grade of malignancy, nuclear polymorphism, rate of mitosis (p < 0.001 respectively) as well as growth pattern (p < 0.01), while biochemical analysis revealed a correlation with nuclear polymorphism (p < 0.05). The correlation analysis of both components of the immunoreactive score revealed a more significant impact of percentage of positive cells than of staining intensity. CONCLUSIONS: Immunohistochemistry detected a closer correlation between prognostic factors and receptor data than biochemical analysis.

Adult↗

[Adjuvant hormonal therapy in lymph node-negative breast carcinoma patients in the postmenopause].

The effect of adjuvant treatment with tamoxifen on recurrence and survival rates was determined in a prospective randomized trial in 98 postmenopausal women (mean age 62.7 [49-77] years) with lymph node-negative breast cancer who had undergone modified radical mastectomy with axillary lymphadenectomy. The tamoxifen group (n = 48) received 10 mg of the drug twice daily for one year. After a mean period of 8 (6-11) years the tamoxifen group had a significantly higher rate of survival without recurrence than the control (no tamoxifen) group (83% vs 61.5%, P = 0.02) and a higher overall survival rate (95% vs 81.9%, P = 0.05). These results indicate that adjuvant tamoxifen favourably influences the prognosis for postmenopausal women with lymph node-negative breast cancer after radical mastectomy with axillary lymphadenectomy.

Breast Neoplasms↗

Effects of the duration of therapy with the LHRH agonist D-ser (BUT)6 Azgly10-LHRH (ICI 118-630) on the steroid hormone content and the morphology of human testicular tissue in the treatment of patients with advanced prostate cancer.

In 20 patients with locally advanced or metastatic prostate cancer, testicular tissue obtained by bilateral subcapsular orchidectomy was examined for steroid hormone content and morphological changes. Eight patients (group I) had not received previous treatment. Twelve patients had been treated with monthly subcutaneous doses of the depot luteinizing hormone-releasing hormone (LHRH) agonist D-ser (BUT)6 Azgly10-LHRH (ICI 118-630). Six patients (group II) had been treated for less than 6 months and 6 patients (group III) for more than 6 months. The longest duration of treatment with depot LHRH was 36 months. After 2 months of treatment (group II), maximum hormone suppression was achieved and remained unchanged even if treatment was continued for 3 years. The mean serum testosterone levels were decreased in group II (means = 0.586 mg/ml) and in group III (means = 0.575 mg/ml) and were found to be in the range of castration; a statistically significant reduction in luteinizing hormone (P less than 0.000001) and follicle-stimulating hormone (P less than 0.05) was observed in the treated patient groups. The content of the steroid hormones dihydroepiandrosterone sulfate (DHEA)-S, testosterone, androstenedione, oestradiol, progesterone and 17-alpha-hydroxyprogesterone/g testicular tissue was significantly lower in patients on LHRH agonists. The differences in concentration were particularly pronounced for DHEA-S, T and A. As in the case of serum concentrations, the testicular tissues showed no differences between groups II and III. In the treated groups a significant reduction in weight was seen, depending on the duration of therapy. Similarly, the structural changes visible by the aid of light and electron microscopes increased with the duration of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Is CA-125 monitoring useful in patients with epithelial ovarian carcinoma and preoperative negative CA-125 serum levels?

Between December 1983 and December 1988 we examined the postoperative tumor marker development and correlated this to the clinical course of the disease in 56 patients suffering from primary epithelial ovarian carcinoma of International Federation of Gynecology and Obstetrics stages I-III and with a preoperative CA-125 serum level less than or equal to 65 U/ml. In 54% of all cases there was a reduction of more than 50% of the CA-125 serum level within the first 3 months after surgery. Nine out of thirteen patients with progressive disease (69%) showed an increasing CA-125 serum level with a median lead time of 6 months (0-11 months) prior to clinical diagnosis. These preliminary results indicate that the monitoring of cancer patients with CA-125 tumor marker seems to be a useful method of early diagnosis of progressive disease even in patients with preoperative serum levels lower than 65 U/ml.

Antigens, Tumor-Associated, Carbohydrate↗

MDR1 gene expression and prognostic factors in primary breast carcinomas.

To prospectively assess the role of the MDR1 gene in breast carcinomas, MDR1 RNA levels of breast carcinoma specimens were determined by slot blot analysis. In 59 evaluable patients with primary breast carcinomas, MDR1 RNA levels of the carcinomas were negative in 54%, low in 29% and high in 17% of the patients. No differences in age, menopause status, oestrogen and progesterone receptor levels, tumour size, lymph node involvement and c-erbB-2/neu gene expression were observed between MDR1 RNA negative patients and MDR1 RNA positive patients.

Adult↗

Breast cyst fluid concentrations of beta-endorphin, steroids and gonadotrophins in premenopausal women with gross cystic disease.

Breast cyst fluid (BCF) and plasma levels of beta-endorphin (beta-EP), oestradiol (E2), progesterone (P), luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), prolactin (PRL) and cortisol were assayed radiochemically in a group of 10 premenopausal women aged 45-50 years suffering from gross cystic breast disease. The concentration of beta-EP (fmol/ml) in BCF (17.6 +/- 4.6 S.E.) was over four times higher than that in plasma (4.2 +/- 0.5 S.E.). The level of E2 was 41 times higher (1738.2 +/- 350.5 S.E. pg/ml) and that of P was 47 times higher (65.47 +/- 8.25 S.E. ng/ml) in BCF than in plasma. The significantly increased values of beta-EP, E2 and P in BCF and the identification of beta-EP in the cyst-lining epithelium indicated that local synthesis occurs. Growth factor-like properties of beta-EP and E2 are responsible for the propagation of cystic changes. The autonomous formation and activity of beta-EP, E2 and P in cystic formations were not correlated with LH, FSH, TSH and cortisol levels, which were significantly higher in plasma than in BCF. The concentration of PRL in BCF was not significantly higher than that in plasma. Moreover, the plasma concentrations of testosterone, androstenedione, thyroxine, triiodothyronine, thyroxine-binding globulin and sex-hormone-binding globulin were within the normal ranges. In this study we demonstrated synergism between beta-EP and steroid hormones which encourages the development of gross cystic disease in premenopausal women.

Estradiol↗

[Ferritin level in newborn infants after prepartal iron medication].

Aim of the study was to find out the influence of iron medication of pregnant women on the iron levels of their newborn. In a prospective randomised study the iron-substituted group (n = 57) was treated with 2 x 1 Aktiferrin comp. Kps. (Merckle) during pregnancy, starting from the 22nd week. The control group (n = 46) had no medication during pregnancy. The substituted group had statistically significantly higher serum ferritin levels in the 30th week of pregnancy (p less than 0.048), higher levels measured in the cord blood at birth (p less than 0.001), and also the newborn of this group had statistically significant higher serum ferritin levels than the newborn of the control group (p less than 0.001). Our conclusion is that prepartal iron medication leads to increased iron stores in the newborn.

Female↗

[Effect of various factors on survival after recurrent and/or metastatic breast cancer].

145 women (22.2%) out of 652 patients with primary breast cancer, who were operated on between January 1980 and September 1988, developed tumour relapse until May 1990. The aim of our retrospective analysis in these 145 patients with local and/or distant tumour relapse was to evaluate the prognostic importance for further survival of the following factors: menopausal status, stage of disease, number of involved axillary lymph nodes, tumour grading, ER and PgR content, postoperative irradiation, adjuvant treatment, localisation of tumor relapse and relapse-free interval. Multivariate stepwise regression analysis of all these factors identified the number of positive axillary lymph nodes (0-3 versus 4+) with a relative risk (RR) of 2.49 and localisation of tumour relapse (local versus visceral metastasis RR = 2.08 and local versus bone metastases RR = 2.08) as the only two significant prognostic factors for further survival. Therefore, these two factors should be stratification criterias for prospectively randomized phase III studies in patients with tumour relapse after primary breast cancer.

Adult↗

Effect of recombinant human erythropoietin on anterior pituitary function in patients on chronic hemodialysis.

In 7 patients with end stage renal failure, anterior pituitary function was tested by simultaneous application of maximally effective doses of the hypothalamic releasing peptides, corticotropin-releasing hormone, growth hormone-releasing hormone, thyrotropin-releasing hormone and gonadotropin-releasing hormone, and compared to 8 normal controls. In addition to the pituitary hormones, plasma cortisol, thyroxine and testosterone concentrations were measured. To test for possible effects of treatment with recombinant human erythropoietin (rhu-EPO), all patients with chronic renal failure were studied again after partial correction of anemia by treatment with erythropoietin. Before initiation of rhu-EPO treatment, plasma concentrations of follicle-stimulating hormone were significantly elevated and the thyroid-stimulating hormone and prolactin responses to thyrotropin-releasing hormone blunted when compared to normal controls. Treatment with rhu-EPO induced a significant increase in plasma ACTH and follicle-stimulating hormone concentrations. All other pituitary functions remained unchanged. Thus, the general improvement in well-being, working capacity and sexual activity cannot be attributed to hormonal changes.

Adrenocorticotropic Hormone↗

Hormonal parameters in androgenetic hair loss in the male.

Alopecia in the male is considered as a genetically determined disorder. Increased local androgen metabolism and androgen receptor binding in the balding areas confirm the importance of the target organ hair follicle as regulative of androgen influences. In our study the hormonal parameters of 65 male patients with male pattern hair loss with a mean age of 24.31 years were compared with those of 58 age-matched controls. Determinations of the androgens, sex-hormone-binding globulin, the hypophyseal hormones luteinizing hormone, follicle-stimulating hormone and prolactin, 17 beta-estradiol and cortisol were performed by standard radioimmunoassay. Significant differences in serum levels of androstenedione, cortisol, 17 beta-estradiol and luteinizing hormone were noted between hair loss patients and control subjects. Suprarenal stimulation as well as hypophyseal feedback mechanisms therefore seem to be involved in male pattern alopecia.

17-alpha-Hydroxyprogesterone↗

Hormone studies in females with androgenic hairloss.

Reports on hormone analysis in androgenic hairloss in the female show partly contradicting results. Elevated as well as normal-range androgen levels have been found. The present study aimed at the investigation of a possibly more differentiated hormonal constellation by hormone analysis and additional determination of the hypophyseal level by the thyrotropin-releasing hormone (TRH) test. In 46 female patients with androgenic hairloss blood sampling for hormone analysis was performed. Determination of the androgens testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS), 17-hydroxy-progesterone acetate (17-OHP) and free testosterone (FT), of sex-hormone-binding globulin (SHBG), estradiol (E2), cortisol (F) and the hypophyseal luteinizing hormone (LH) and follicle-stimulating hormone (FSH) was performed by standard radioimmunoassay methods. The TRH-test is based on feedback mechanisms between the hypothalamic TRH which stimulates hypophyseal TSH and PRL release. Thus, even mild forms of hypothyroidism or hyperprolactinaemia can be detected. The control group for the TRH test consisted of 45 volunteer females without hairloss or any other hormonal or menstrual disturbances. Statistical analysis was performed according to the Wilcoxon two-sample test. The results of the study show no significant elevation of androgens in females with androgenic hairloss, but a more complex condition with involvement of the glandula suprarenalis and the hypophyseal level. Significantly elevated TSH levels prior to and after TRH stimulation in the hairloss group indicate that hypothyroidism may be an important hormonal disturbance in androgenic hairloss. Interactions between hypothyroidism and androgen metabolism are possible at various links.(ABSTRACT TRUNCATED AT 250 WORDS)

17-alpha-Hydroxyprogesterone↗

[Steroid hormone receptors in mammary carcinoma. Immunohistochemical detection and prognostic significance].

Estrogen and progesterone receptors were immunohistochemically recorded from 426 cases of primary mammary carcinoma. Immunohistochemical detection was based on monoclonal antibodies to estrogen receptor (H222) and progesterone receptor (KD68). Immunohistochemical and biochemical tests were correlated to each other with significance (p less than 0.0001) for either receptor. Some of the histological parameters exhibited relationships with the immunohistochemical receptor status. Receptor positivity of lobular, mucoid, tubular, and papillary carcinomas was more frequent than that of ductal carcinoma, whereas that of medullary carcinoma fell below ductal cases. A straight forward correlation of statistical significance was found to exist between histological tumor grade and steroid hormone receptor status. Receptor positivity of carcinomas with sizeable stroma components proved to be more frequent than that of carcinomas with lower stroma levels. Steroid hormone receptors can be immunohistochemically identified from cytological specimens, as well, though some limiting factors are implied in the latter. Thirteen percent of fine-needle aspirates provided falsely negative steroid hormone receptor findings, as compared to histological biopsy. This problem was encountered primarily in cases of low receptor positivity and high stroma content of carcinoma, factors for which only minor amounts of cell material could be obtained from puncturing. Clinical follow-up checks and evaluation of survival data revealed the immunohistochemically determined steroid hormone receptor status to be of significant importance to prognostication (ER-ICA p less than 0.00001; PgR-ICA p = 0.004). The prognosis of patients with negative estrogen and progesterone receptors was found to be worse than that of patients with positive receptor status. These studies are likely to confirm immunohistochemical determination of steroid hormone receptors, using monoclonal antibodies, to be a reliable method of great prognostic importance.

Adenocarcinoma↗

[Steroid hormone receptors in synovial tissue].

Among the variety of symptoms of the postmenopausal syndrome joint pain seems to be an important problem for the patient as well as for her doctor. Because of the excellent response of the hormone substitution therapy it is asked if the synovial membrane is a target organ for oestradiol. Biopsies from the knee joint of ten women (not having any hormone therapy)--excised during knee joint surgery--were examined. Only in two cases oestrogenreceptors were found. Accordingly the synovial membrane cannot be seen as a direct target organ for oestradiol and so other mechanisms must play a role in the pathogenesis of postmenopausal joint pain.

Adolescent↗

Fertility, pregnancies and offspring complications after bone marrow transplantation.

Hormonal assessment including luteotropic hormone (LH), follicle stimulating hormone (FSH), testosterone (T), oestradiol and sex hormone binding globulin was performed 1-6 years after allogeneic, syngeneic and autologous bone marrow transplantation in nine patients with severe aplastic anaemia (SAA) and 14 patients with haematological malignancy (HM). Among nine allografted SAA patients, seven aged less than 26 years showed normal gonadal function while two women above 26 years had premature ovarian failure. All eight female patients transplanted for HM had premature ovarian failure. Among six male patients transplanted for HM, four have elevated FSH but normal LH and T levels, while two have normal LH, FSH and T levels or elevated LH and FSH levels but decreased T levels, respectively. Three patients transplanted for SAA (two female, one male), but none of those transplanted for HM, parented four healthy children. A high incidence of offspring complications was noticed, including (i) persistence of fetal circulation syndrome, (ii) erythroblastosis fetalis, and (iii) prolonged newborn icterus. One female patient transplanted for SAA had an abortion in the 25th week of gestation. These observations confirm previous reports on recovery of fertility, mainly in younger patients transplanted for SAA; there was, however, an unexpectedly high incidence of pre-, peri- and postpartum complications in the offspring of bone marrow graft recipients.

Adolescent↗

[Hyperprolactinemia and hypophyseal hypothyroidism as cofactors in hirsutism and androgen-induced alopecia in women].

A more comprehensive hormonal diagnosis than has previously been performed shows that androgen-dependent diseases of hair growth are due to more varied hormonal disturbances than elevated androgen serum levels alone. In 46 female patients with androgenic hair loss and 27 patients with hirsutism, the levels of the androgens testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulphate and 17-hydroxyprogesterone and of sex hormone-binding globulin, cortisol, oestradiol and the hypophyseal hormones follicle-stimulating hormone and luteinizing hormone were determined and compared with the hormone levels of 27 female patients without endocrine disorders. Of the androgens, only androstenedione showed a slightly significant elevation in hirsutism. Cortisol was elevated significantly in androgenic hair loss, and with a low degree of significance in hirsutism. In view of the complex hormonal interactions of thyroxin, prolactin and androgens and thyroid hormones the thyrotropin-releasing hormone (TRH)-stimulation test was performed in 38 female patients with androgenic hair loss and 27 with hirsutism, and the results were compared with those recorded in 45 female control persons. The test is based on feedback mechanisms between hypothalamic TRH and hypophyseal TSH and prolactin and peripheral thyroid hormones. Baseline concentrations of TSH prior to stimulation were significantly elevated in hirsutism, while in androgenic hair loss both baseline and stimulated TSH levels were significantly elevated; thus, hypothyroidism is a significant finding in both clinical pictures. In the case of prolactin, both baseline and stimulated levels were highly significantly elevated in hirsutism, while in androgenic hair loss the stimulated levels were significantly elevated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗