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Biomedical subjects

L Skoog

Publications and source records attributed to L Skoog.

At least 91 records · Page 5Linked to original sources

Estrogen and progesterone receptor content in breast epithelial cells from healthy women during the menstrual cycle.

OBJECTIVE: Our objective was to analyze the presence of estrogen and progesterone receptors in breast epithelial cells from healthy women during the follicular and luteal phase of the menstrual cycle. STUDY DESIGN: We analyzed estrogen receptor and progesterone receptor variations in breast epithelial cells procured through fine-needle aspiration biopsy from 42 healthy volunteers during the menstrual cycle using immunocytochemical receptor analysis. Differences were assessed by chi 2 test and the Wilcoxon rank sum tests. RESULTS: Estrogen receptor was detected more often in women aspirated in the follicular (68%) than in the luteal (32%) phase (p < 0.001); progesterone receptor was detected in around 80% in both phases. In ovulating women who were aspirated twice during the same menstrual cycle the proportion of estrogen receptor-positive cells was reduced from 20% to 4% (p < 0.02); the progesterone receptor values were 17% and 24%. CONCLUSION: Our data indicate an important difference in progesterone receptor variation in the breast as compared with the endometrium.

Adult↗

Immunohistochemical analysis of oestrogen and progesterone receptors in endometriotic tissue and endometrium.

The objective of the study was to compare the localization and staining intensity of oestrogen and progesterone receptors in endometrium and endometriotic tissue. Using monoclonal antibodies towards oestrogen and progesterone receptors, analysis was performed in 63 endometriotic samples from 40 women and compared to endometrium obtained simultaneously from 25 of the women. Using a staining index, 'total immuno-staining score', calculated from the staining intensity multiplied by the fraction of positive cells, the receptor content was estimated semiquantitatively. The scores for both oestrogen and progesterone receptors were lower in endometriotic epithelial cells than in endometrial epithelial cells, but the differences reached statistical significance only for the progesterone receptor. No difference was found for stromal cells. There was a significant correlation between oestrogen receptor score in endometriotic tissue and in endometrium, but not for progesterone receptor score. In endometrium and vaginal and peritoneal endometriosis, the progesterone receptor score showed similar values, higher than those in ovarian endometriosis. The data from this large immunohistochemical study support previous results of quantitative steroid receptor analyses, indicating that the regulation of steroid effects, especially those of progesterone, differs between endometriotic and endometrial tissue.

Adult↗

S-phase fraction is a prognostic factor in stage I breast carcinoma.

PURPOSE AND METHODS: The prognostic significance of cell proliferation, estimated as cytometric S-phase fraction (SPF), was investigated in node-negative breast cancer patients with small tumors (T1, NO). The 219 stage I patients originated from two series and were diagnosed either from 1978 to 1981 or from 1981 to 1985. The tumors were analyzed for estrogen receptors (ERs) by isoelectric focusing and for cellular DNA content by static cytofluorometry or flow cytometry. RESULTS: A high SPF correlated with the absence of ERs and abnormal DNA content, and was less often found in tumors smaller than 11 mm compared with those with a diameter between 11 and 20 mm. Among the variables age, tumor size, DNA ploidy, ER status, and SPF, only SPF showed a significant association with distant recurrence and breast cancer survival in systemically untreated patients. The relative recurrence rate for patients with an SPF of 10% or greater was three times that for patients with lower SPFs. Estimated 8-year breast cancer survival rates for the same groups were 72% and 91%, respectively. CONCLUSION: This study suggests that cytometric SPF has prognostic significance in stage I breast carcinoma.

Analysis of Variance↗

Immunohistochemistry and biochemistry in detection of androgen, progesterone, and estrogen receptors in benign and malignant human prostatic tissue.

The relative distribution of androgen (AR), progesterone (PR), and estrogen receptors (ER) was localized and estimated in human prostate tissue by immunohistochemistry in five normal tissue samples, in eight benign hyperplastic (BPH) samples, in nine primary cancers, and in seven prostate cancer metastases. Moreover, three prostatic cancer cell lines (LNCaP, DU 145, and PC 3) were analyzed. A comparison between the results obtained by radioligand binding assays and immunohistochemistry was performed for the AR and PR. Using immunohistochemistry, the AR was exclusively detected in the nuclei of both benign and malignant prostatic epithelial cells. The highest proportion of AR-positive cells was found in BPH and in prostate cancer metastases as compared with normal prostatic tissue. In a majority of the cases, the PR was only present in the nuclei of stromal cells. Benign hyperplastic prostates contained higher proportions of PR-positive cells as compared with primary carcinoma. PR was sparse in epithelial cells. ER-positive stromal cell nuclei were only detected in carcinomatous prostates. A few ER-positive epithelial cell nuclei were found in one sample each of a BPH and normal prostate. All cells from the androgen-dependent, LNCaP, cell line and a majority of the cells from the androgen-independent, DU 145, cell line were AR-positive. In contrast, the cells from the androgen-independent, PC 3, cell line were all AR-negative. All three cell lines were PR- and ER-negative. The radioligand binding technique detected the AR in extracts from both the cytosol and the nucleus. Again BPH contained higher amounts of AR as compared with normal prostatic tissue. The LNCaP cells contained high amounts of cytosolic AR while cells from the DU 145 and PC 3 cell lines lacked detectable AR as estimated by biochemical techniques. There seemed to be a discrepancy between biochemically measured and immunohistochemically estimated receptor content.

Epithelium↗

Prognostic factors and natural history in lymph node-negative breast cancer patients.

The prognostic significance of clinical and histological factors as well as hormone receptors was analyzed in a population of 3,064 lymph node-negative breast cancer patients operated in the Stockholm region between 1976 and 1988. None of these patients received systemic adjuvant treatment. Multivariate analysis showed that only histological tumor size, number of examined axillary lymph nodes, and progesterone receptors were independent prognostic factors in terms of recurrence-free interval. An individual risk of recurrence was calculated taking into account these three factors to discriminate between three groups of patients with a risk of less than 15%, 15-25%, and more than 25% of recurrence at 5 years. Similar results were obtained taking into account only the first two factors. The prognostic information added by the knowledge of progesterone receptors only changed the recurrence rate in approximately 3%. This study showed that conventional prognostic factors permit the identification of high risk lymph node-negative breast cancer patients. Results obtained by the use of new more sophisticated factors should be compared with those obtained analyzing strong conventional prognostic factors.

Breast Neoplasms↗

Immunocytochemical analysis of receptors for estrogen and progesterone in fine needle aspirates from anal epidermoid carcinoma.

Fifteen patients with anal epidermoid carcinoma were examined with percutaneous or transanorectal fine needle aspiration (FNA) cytology. Aspirates from all patients allowed cytologic verification of the diagnosis. Estrogen receptor (ER) and progesterone receptor (PgR) were analyzed using an immunohistochemical technique well adapted for steroid receptor analysis in hormone-dependent carcinomas. Neither ER nor PgR could be detected in any of the aspirates. This finding is somewhat unexpected since there is a strong female predominance in this tumor type. However, our findings do not negate that sex steroid hormones may indirectly play a role in the tumorigenesis of anal epidermoid carcinoma.

Adult↗

Measurement of interferon sensitivity in tumour cells from fine-needle aspirations.

Previous studies have shown significant correlations between interferon (IFN) induced enhancement of the enzyme 2',5'-oligoadenylate (2',5'-A) synthetase in vitro and response to IFN therapy. A limitation of this and other predictive tests is the availability of malignant cells for culture. Malignant cells can be obtained from most palpable solid tumours by fine-needle aspiration. We investigated whether malignant cells from such aspirations can be used in a 2',5'-A synthetase assay. In 23/27 (85%) of the cases sufficient amounts of viable cells were obtained, containing a high proportion (greater than or equal to 90%) of tumour cells. In 13/23 tumour samples (57%) IFN-alpha significantly enhanced the 2',5'-A synthetase levels. The use of cells from the fine-needle aspirations for prediction of IFN sensitivity, makes the 2',5'-A synthetase test applicable in a wide range of tumours at a variety of disease stages.

2',5'-Oligoadenylate Synthetase↗

Immunocytochemical detection of the androgen receptor in fine needle aspirates from benign and malignant human prostate.

A monoclonal antibody to the androgen receptor was applied to fine needle aspirates from patients with benign and malignant prostatic disease. The series includes six patients with benign hyperplasia and 24 patients with prostatic carcinomas. The androgen receptor was detected in most nuclei of both benign and malignant epithelial cells. The intensity of immunostaining varied. No obvious relation was observed between the intensity of the staining in benign versus malignant cells. In addition no clear differences were found in the proportion of androgen receptor positive cells in benign aspirates as compared with aspirates from well differentiated or moderately well differentiated prostatic carcinomas. The relative number of androgen receptor positive cells was highest in smears from poorly differentiated prostatic carcinomas.

Antibodies, Monoclonal↗

Fine needle aspiration cytology of high grade T-cell lymphomas in human T-lymphotropic virus type 1 carriers.

We studied the fine needle aspiration (FNA) cytology of high grade peripheral T-cell lymphomas from eight human T-lymphotropic virus-1 (HTLV-1) positive patients. FNA smears from seven lymphomas showed a distinctive cytologic pattern with a dominance of rounded cells with irregular nuclei and a moderately basophilic cytoplasm. Irregular cells with a pale abundant cytoplasm were present in varying amounts. Some smears contained a few giant cells with cerebriform nuclei. In addition, plasma cells and eosinophils were found. Epithelioid cells were an inconstant finding. On histology these seven lymphomas were assigned to the pleomorphic medium-large cell subtype and all but one were of T-helper phenotype with rearrangements of the T-cell receptor. FNA smears from a lymph node in a patient with a previous histological diagnosis of lymphomatoid papulosis of the gingiva showed a monotonous pattern of large immunoblastic cells with some binucleated variants consistent with a diagnosis of high grade immunoblastic lymphoma, which was confirmed histologically. Our results show that peripheral T-cell lymphomas from HTLV-1 positive patients have cytological patterns which are distinctive enough to allow a conclusive diagnosis of high grade T-cell lymphoma. However, we do not think that the cytology of HTLV-1 positive lymphomas can be differentiated from that of virus-unrelated high grade T-cell lymphomas.

Adult↗

Prognostic significance of axillary nodal status in primary breast cancer in relation to the number of resected nodes. Stockholm Breast Cancer Study Group.

The prognostic significance of the number of metastatic axillary lymph nodes in relation to the number of identified nodes among 1,622 patients with operable breast cancer was assessed. We present a Cox's analysis of the prognostic significance of nodal status in relation to loco-regional recurrence, axillary recurrence, distant metastasis and death due to breast cancer respectively. As expected, the relative risks were generally higher for patients with nodal involvement, particularly those with 4 or more positive nodes or with few examined nodes. However, among those with more than 4 positive nodes the risk of distant metastases and death due to breast cancer was about the same irrespective of the number of nodes examined.

Antineoplastic Agents↗

Analysis of hormone receptors and proliferation fraction in fine-needle aspirates from primary breast carcinomas during chemotherapy or tamoxifen treatment.

Twelve postmenopausal women (54-93 years) with primary breast carcinoma were treated with tamoxifen due to infirmity or refusal to undergo surgery. Seven premenopausal patients (32-50 years) were given preoperative chemotherapy because of large tumors or inflammatory carcinoma. Fine-needle aspiration biopsy was used to procure tumor cells for diagnosis, hormone receptor determination and analysis of proliferation fraction. Aspirations were repeated every 3 months in the tamoxifen group and each month in patients receiving chemotherapy. Two patients who responded to tamoxifen had tumors with more than 75% estrogen receptor positive cells. A decreased proliferation fraction was observed in two tumors responding to tamoxifen. Eight patients, all with estrogen receptor positive tumors, had stable disease. Progressive disease was observed in two patients with less than 25% receptor positive cells. In these tumors the percentage of proliferating cells remained high during therapy. Objective response was recorded for six patients treated with chemotherapy. The clinical response was reflected in a decreased proliferation fraction. No correlation was observed between response and percentage of proliferating cells in the untreated tumor. The results suggest that analysis of tumor cell characteristics such as hormone receptor content and proliferation fraction can be used to predict and monitor response to endocrine treatment and chemotherapy in breast carcinomas.

Adult↗

Randomized trial of adjuvant tamoxifen in node negative postmenopausal breast cancer. Stockholm Breast Cancer Study Group.

The paper presents long-term results of a randomized trial of adjuvant tamoxifen (40 mg daily for 2 or 5 years) versus surgery alone including 1,347 postmenopausal patients with histologically negative axillary nodes and a tumour diameter less than or equal to 30 mm. Data on the estrogen receptor status of the primary tumour were available in 1,136 patients (84%). At a median follow-up of 7 years (range 1.7-13.0 years) there was a significant prolongation of the recurrence-free survival among those allocated to tamoxifen (p less than 0.01), significantly fewer deaths due to breast cancer (p = 0.02) and a trend towards improved overall survival (p = 0.11). The treatment benefit was restricted to patients with ER-positive tumours. There was no significant reduction of breast cancer recurrences in the tamoxifen group among patients whose tumours were classified as ER-negative. The results support and extend previous studies in showing a long-term benefit of tamoxifen in postmenopausal breast cancer patients with node-negative, estrogen receptor positive disease.

Breast Neoplasms↗

Oestrogen, progesterone, and glucocorticoid receptors in normal and neoplastic parathyroid glands.

OBJECTIVE: To verify the presence or absence of steroid receptors in the parathyroid glands of patients undergoing operations on the parathyroid and thyroid glands. DESIGN: Open experimental study. SETTING: Karolinska Hospital, Stockholm, Sweden. MATERIAL: 165 parathyroid glands from 137 patients, 108 of whom underwent operations on the parathyroid glands and 29 on the thyroid gland. INTERVENTIONS: Normal and neoplastic parathyroid tissue was analysed for its content of oestrogen and progesterone and glucocorticoid receptors using either ligand binding or antibodies raised against oestrogen and progesterone receptors. RESULTS: Positive reactions to female sex steroid receptors (defined as > 0.05 fmol/microgram DNA) were uncommon (9%) regardless of the morphological classification of the glands or the age, sex, and menopausal status of the patients. Glucocorticoid receptors were detected in 107/163 (66%) of all glands analysed (mean value 0.43 fmol/micrograms DNA, range 0-44). Seventy of the 96 diseased glands (73%) contained receptors, as did 27/67 normal glands from patients with primary hyperparathyroidism or those undergoing thyroid operations. The difference was again not associated with age, sex, and menopausal status. CONCLUSIONS: It seems unlikely that sex steroid hormones play a physiological part in the secretion of parathyroid hormone, but our finding of glucocorticoid receptors in normal as well as diseased parathyroid tissue suggests that they may have a role in the regulation of parathyroid function.

Adult↗

Immunohistochemical c-erbB-2 protooncogene expression and nuclear DNA content in human mammary carcinoma in situ.

Immunohistochemical c-erbB-2 proto-oncogene expression and nuclear DNA distribution patterns were assessed in 119 formalin-fixed paraffin-embedded surgical specimens of human mammary carcinomas in situ (CIS). The series consisted of 107 ductal carcinomas in situ (DCIS), 9 lobular carcinomas in situ, and 3 cases of Paget's disease of the nipple. Nuclear DNA distribution patterns were assessed by image cytometric analysis of histopathologically identified cell nuclei. Fifty-one of 107 (48%) DCIS were immunoreactive for c-erbB-2, whereas specific cell membrane staining was absent in lobular carcinomas in situ. The neoplastic cell nuclei of 46 CIS (39%) were of DNA diploid type, and 73 CIS (61%) contained aneuploid nuclear DNA. Among various histopathologic subtypes of DCIS, significant differences in c-erbB-2 immunoreactivity and nuclear ploidy were observed. DCIS of the comedo type most often were c-erbB-2 positive and exhibited aneuploid nuclear DNA histograms. DCIS of micropapillary type was the second most frequently reactive c-erbB-2 expression, and aneuploidy were less common in solid, cribriform, and papillary DCIS. The results of the current study indicate that immunohistochemical expression of the c-erbB-2 proto-oncogene product is closely related to the histopathologic subtype and the nuclear DNA content of mammary CIS. Examples of CIS that are c-erbB-2 immunoreactive and DNA aneuploid seem to have a significantly higher risk for the subsequent development of infiltrating mammary carcinoma.

Biomarkers, Tumor↗

The DNA profile of breast cancer in situ.

The nuclear DNA content of 46 mammary adenocarcinomas in situ was measured by means of image cytometry in 4-microns-thick Feulgen-stained histological sections. Aneuploidy was found in 23 cases (50%), whereas the other 23 cases exhibited a diploid DNA distribution pattern. Intraductal carcinoma, the most common subtype in the present study, was found to be aneuploid in 19 cases (63%), with the comedo variant showing aneuploidy in as many as 10 of 11 cases (91%). In contrast, lobular and papillary carcinoma in situ exhibited only 17% and 0% aneuploidy, respectively. The percentages of aneuploid and diploid DNA profiles of the in situ lesions in the present study are almost identical to those observed in invasive breast adenocarcinoma. This indicates that the DNA distribution pattern characteristic for an individual breast adenocarcinoma is already established at the in situ stage, i.e., it occurs before invasiveness and does not progress from a euploid to an aneuploid pattern. In clinical routines DNA ploidy measurements may be of help to distinguish between e.g., hyperplasias and in situ lesions and may also indicate in which direction the malignancy potential of in situ lesions will develop.

Adult↗

Contralateral primary tumors in breast cancer patients in a randomized trial of adjuvant tamoxifen therapy.

Prophylactic treatment with the anti-estrogen tamoxifen may reduce the risk of breast cancer because estrogens are thought to act as promoters in the pathogenesis of the disease. This article presents results on the incidence of contralateral new primary tumors among 1846 postmenopausal breast cancer patients included in a randomized trial of adjuvant tamoxifen therapy for 2 or 5 years after surgery versus no adjuvant endocrine therapy. The median follow-up was 7 years (range, 3-13 years). There was a significant reduction of contralateral breast cancer in the 931 patients in the tamoxifen group versus that in the 915 control patients (29 versus 47 cases, respectively; P = .03). The cumulative incidence at 10 years in the tamoxifen group and the control group was 5% and 8%, respectively. Analysis of the relative hazard of contralateral tumor over time showed that the benefit with tamoxifen therapy was greatest during the first 1-2 years, but there was a continued risk reduction during the entire follow-up period, i.e., more than 10 years after cessation of treatment. There was no significant difference in the number of contralateral cancers in the patients randomly assigned to 2 or 5 years of treatment, but the 95% confidence interval of the relative hazard was wide. The proportion of estrogen receptor-negative contralateral breast cancers was higher in the tamoxifen group than in the control group. There was no difference, however, between the two groups in recurrence-free survival time from the diagnosis of the contralateral cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Comparison of transrectal prostate digital aspiration and ultrasound-guided core biopsies in 99 men.

We compared digital transrectal needle aspiration and transrectal core prostate biopsies obtained with ultrasound guidance in 99 men. Both procedures were effective in identifying prostate cancer; complete sensitivity was 94 percent for aspiration and 90 percent for core biopsy. Aspiration confirmed 87 percent of 38 known cancers and 94 percent of 81 cancers overall, compared with 82 percent and 90 percent with core biopsies. The greatest number of cancers was found when both procedures were considered (95% of known and 98% of all cancers). Grading of both specimens was performed but was not equivalent. Unsatisfactory or inconclusive results by either procedure often obtained when cancer was present. We suggest digital transrectal needle aspiration as a first means of identifying most palpable prostate lesions. Transrectal core biopsies guided by ultrasonography should be used when suspicion of cancer cannot be confirmed by aspiration and when there is no palpable lesion (but clinical suspicion of cancer).

Adenocarcinoma↗