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L Skoog

Publications and source records attributed to L Skoog.

At least 181 records · Page 10Linked to original sources

Expression of sex steroid receptors and IGF-1 mRNA in breast tissue--effects of hormonal treatment.

The mechanisms behind increased breast tissue proliferation and a possibly increased breast cancer risk in women using hormonal contraception (HC) and hormonal replacement therapy (HRT) are incompletely understood. We analyzed breast tissue from 20 premenopausal and seven postmenopausal women undergoing reduction mammoplasties for estrogen receptor (ER) and progesterone receptor (PR) content as well as mRNA levels for ER, PR and insulin-like growth factor-1 (IGF-1). The receptor values were correlated to IGF-1 mRNA concentrations and levels of steroid and peptide hormones and SHBG. In women using HC, we found significantly lower ER values (p = 0.02) but non-significantly lower ER mRNA levels compared to those in naturally cycling women. PR and PR mRNA were no different. Women on HC displayed a higher breast tissue proliferation (p = 0.05) expressed as Ki-67, MIB-1 positivity, which was correlated with IGF-1 mRNA (r(s) = 0.82, p = 0.04). Since the concentration of sex steroid receptors in breast tissue is comparatively low and steroid receptors are down-regulated during hormonal treatment, mechanisms other than direct sex steroid receptor action are likely to be present. Our results suggest a role for IGF-1 in the proliferative response of breast tissue during exogenous hormonal treatment.

Adult↗

Fine needle aspiration cytology of penile tumors.

OBJECTIVE: Penile tumors are unusual and can represent neoplastic or inflammatory processes. We report a series of penile tumors diagnosed by fine needle aspiration (FNA) cytology. STUDY DESIGN: Files from the Division of Clinical Cytology, Karolinska Hospital, were searched, and cases of FNA cytology of the penis selected. Clinical information and cytologic diagnoses were recorded and observations from aspiration smears made. RESULTS: Eleven patients had presented to Karolinska Hospital for FNA cytology of the penis. They ranged from 46 to 89 years of age; all were uncircumcised. Tumors were present in various locations, including the glans and shaft. Five patients had squamous cell carcinoma (SCCA) of the penis; three were primary, one locally recurrent and one metastatic from primary lung SCCA. There were three carcinomas metastatic from primary colon, prostate and bladder tumors. There was one each of locally recurrent malignant melanoma, locally metastatic testicular mesothelioma and Peyronie's disease. Discomfort associated with the procedure was tolerable, there were no complications, and each biopsy provided sufficient material for a cytologic diagnosis. CONCLUSION: FNA cytology of penile tumors is a successful, well-tolerated procedure capable of providing a cytologic diagnosis and useful information for patient management.

Adenocarcinoma↗

DNA distribution, cytosol estrogen receptors and axillary nodes as prognostic predictors in breast carcinoma.

One hundred and fifty patients with breast carcinoma were examined to compare axillary node status, estrogen receptor level and cellular DNA content as prognostic indicators. Seventy-four per cent of the patients were postmenopausal and forty per cent had axillary node metastases. Estrogen receptor was measured by isoelectric focusing in polyacrylamide gel. DNA was measured in individual cell nuclei by means of Feulgen-acriflavine-sulphate stained imprints. Fifty-two per cent of the tumors had diploid and/or tetraploid DNA pattern, and the rest aneuploid pattern. Axillary node metastases, aneuploid DNA pattern and low level of estrogen receptor were related to recurrence. When introduced into Cox's proportional hazards procedure, axillary nodes and estrogen receptor level but not DNA pattern remained as significant predictors of recurrence.

Adult↗

Prognostic importance of the uPa/PAI-1 complex in breast cancer.

The complex between urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 (plasminogen activator inhibitor 1) has been prognostically evaluated in patients with breast cancer. The concentrations of uPA antigen, PAI-1 antigen and the uPA/PAI-1 complex were analysed in extracts from breast cancer tumours from 233 patients (median follow-up of patients: 71months). The uPA/PAI-1 complex typically constituted about 5% of the uPA antigen (total uPA). The concentration of complex was found to correlate more strongly to the concentration of PAI-1 (r = 0.72; p < 0.0001) than to the concentration of uPA (r = 0.55: p < 0.0001). Interestingly, in this material the uPA/PAI-1 complex (using an optimised cutoff level of 0.22 ng microg(-1) DNA) had a stronger prognostic value than optimised cut-off valuesfor uPA or PAI-1. The data suggest that activation of prourokinase within the tumour, which is a prerequisite for the formation of the uPA/PAI-1 complex, is of better prognostic value than the production of prourokinase or PAI-1 in the breast cancer tumour.

Adult↗

Receptors for estrogen and progesterone in breast carcinoma in situ.

In contrast to the situation in invasive breast carcinoma, there are only few reports on the levels of receptors for estrogen (ER) and progesterone (PgR) in pre-invasive (in situ) breast carcinoma. In the present study ER and PgR levels were analyzed in 57 in situ human mammary carcinomas using a quantitative enzyme immunoassay method. Intraductal carcinoma was the dominating histopathological subgroup (75%). Within this subgroup the non-comedo and comedo variants comprised 66 and 34 percent respectively. Intralobular and papillary in situ subtypes were the second most frequent subgroups, representing 11% each. Using a cut-off level of 0.05 fmole/microgram DNA to define receptor poor and rich tumors we found that thirty-one out of the 57 cases (54%) were ER-rich. In the ER-rich tumors the receptor levels varied between 0.05 and 6.50 fmole/microgram with a mean concentration of 0.80 fmole/microgram DNA. Fifteen of 51 (30%) tumors were classified as PgR-rich tumors in which the levels ranged between 0.05 and 2.90 fmoles/microgram DNA, with a mean concentration of 0.45 fmoles/microgram DNA. Two thirds of the non-comedo, lobular and papillary variant were ER rich. A majority (80%) of comedo tumors were ER poor. Our findings show that 54% of in situ breast carcinomas have the molecular prerequisites for response to antiestrogen therapy which is of interest when planning adjuvant treatment protocols.

Breast Neoplasms↗

Heterogenous expression of the EGF-receptor in human breast carcinoma.

The epidermal growth factor receptor was analyzed in the membrane fraction from a series of human breast carcinomas using a radioligand assay. The results were compared to immunostaining with monoclonal antibodies on tissue sections. All tumors with detectable receptor levels as measured by ligand binding showed a positive staining with monoclonal antibodies. In such tumors more than 50 percent of the cells were receptor positive with varying intensity. Tumors classified as receptor negative with the radioligand assay could be divided into two major groups based on their immunostaining. The largest group showed no reactivity with monoclonal antibodies. In a second smaller group, a positivity was observed in small clusters of tumor cells while the majority of cells were negative. The staining intensity in such clusters was usually low. It seems possible that this heterogenous expression of the epidermal growth factor receptor is of significance with respect to clonal selection in tumor spreading.

Antibodies, Monoclonal↗

Synergistic inhibitory effect of gamma-interferon and EGF on A431 cells.

Addition of high concentrations (100ng/ml) of epidermal growth factor (EGF) to cultures of the epidermoid-carcinoma cell-line A431, which expresses high levels of the EGF receptor, resulted in 50 percent reduction in growth rate. At a lower level (10 ng/ml) of EGF no such inhibitory effect was observed. Addition of gamma-interferon at a concentration of 100 u/ml, but not alpha-interferon at the same concentration. inhibited the growth rate of A431 cells by 50 percent. Incubation of the cells in medium containing both 10 ng/ml of EGF and 1000 u/ml of gamma-interferon led to a complete growth arrest. After 48 hours this inhibition was not reversible and resulted in excessive cell-death after approximately seven days. The human lung cancer cell-line U-1752, which expresses low levels of the EGF receptor, was not inhibited by EGF even at high concentrations. Gamma-interferon did not increase the sensitivity of these cells to EGF. The results show that the modulating effect of gamma-interferon on EGF activity is variable and probably depends on cell line, receptor concentration as well as the primary effect of EGF on different cells.

Carcinoma, Squamous Cell↗

Cytology and immunocytochemistry of bilateral breast metastases from prostatic cancer. Report of a case.

The cytologic findings in fine needle aspirates of a previously treated prostatic cancer metastatic to both breasts in a 65-year-old man are described. The prostatic origin of the poorly differentiated adenocarcinoma cells was demonstrated by identification of cytoplasmic prostate-specific antigen. The clinical importance of a conclusive diagnosis differentiating a primary from a metastatic lesion is discussed; this case illustrates the value of immunocytochemical analysis as an aid to cytomorphologic diagnosis in making such determinations.

Adenocarcinoma↗

Fine needle aspiration cytology and immunocytochemistry in the diagnosis of lymphoid lesions of the thyroid gland.

Immunocytochemical analysis was used in conjunction with cytomorphology to evaluate fine needle aspirates from 18 patients with nodular lymphoid infiltrates of the thyroid. The smears from 13 patients had a cytomorphology that was diagnostic of chronic lymphocytic thyroiditis; immunocytochemistry showed the lymphoid population to be composed of T cells and polyclonal B cells. Three patients had high-grade malignant lymphomas by cytomorphology; immunologic evaluation showed the B-cell phenotype of the lymphoma cells and monoclonal light chain expression. Cytomorphology could not differentiate between an inflammatory and a neoplastic lymphoid infiltrate in two cases. Immunocytochemical analysis showed that the cells of B-cell phenotype were monoclonal (neoplastic) in one case and polyclonal (inflammatory) in one case.

Adult↗

Transforming growth factor alpha in human mammary carcinomas and their metastases.

A binding competition assay was used to measure the content of transforming growth factor alpha in human mammary carcinomas and their metastases. Thirty one percent of the primary and 50 percent of the metastases expressed the transforming growth factor alpha with values ranging between 1.6 to 278 EGF equivalent ng/mg tumour extract protein. There was no correlation between the transforming growth factor alpha content and the estrogen receptor value.

Breast Neoplasms↗

Cytomorphology and immunocytochemistry of fine needle aspirates from blastic non-Hodgkin's lymphomas.

Fine needle aspirates from 54 consecutive patients with primary or recurrent blastic (high-grade malignant) non-Hodgkin's lymphomas (NHLs) were analyzed by cytomorphology and immunocytochemistry. The cytologic diagnoses induced follicular center-cell-derived (centroblastic or anaplastic centrocytic) lymphoma (31 cases), immunoblastic lymphoma (11 cases), lymphoblastic lymphoma (9 cases) and histiocytic lymphoma (3 cases). Immunocytochemistry showed a B-cell phenotype of the neoplastic lymphocytes in all lymphoblastic lymphomas, 29 follicle center-cell lymphomas and 4 immunoblastic lymphomas. Four of the immunoblastic lymphomas were of T-cell origin while one case was not evaluable due to necrosis. A histiocytic origin was confirmed in two of the three cases that had a cytologic diagnosis of histiocytic lymphoma; the third case was shown by immunocytochemistry to be a true Ki-1-positive large cell lymphoma. Histologic and immunohistochemical analysis were performed on surgical biopsies from 18 patients. The results were in agreement with those on the fine needle aspiration (FNA) material in 14 cases. Three lymphomas could be phenotyped on aspirated material while marker studies on excised material were inconclusive. One lymph node aspirate contained mostly necrotic cells, which were unsatisfactory for adequate immunocytochemistry. However, sections from a removed tonsil from the same patient could be used for conclusive histology and phenotyping. In conclusion, the high diagnostic accuracy of combined cytomorphologic and immunocytochemical assessment of FNA samples validates the use of the technique in the diagnostic work-up of blastic (high-grade malignant) NHLs. In fact, the diagnostic accuracy seems so high that the technique can safely be used in the final diagnosis of blastic NHLs.

Adult↗

Receptors for epidermal growth factor and sex steroid hormones in human colorectal carcinomas.

Iodinated epidermal growth factor was used to identify its specific receptor in 32 human colorectal carcinomas. The receptor was found in 25% of the tumors with values between 6.9 - 104.0 fmoles/mg DNA. Receptors for estrogen and progesterone were detected in 45 and 25% of the tumors respectively. No correlation was observed between short term survival and content of receptors for sex steroid hormones. Four of the 8 patients with detectable levels of epidermal growth factor receptor had experienced relapse.

Carcinoma↗

Biodistribution of radioactive epidermal growth factor in normal and tumor bearing mice.

The biodistribution of iodinated epidermal growth factor in normal and tumor bearing mice was analyzed. The uptake of epidermal growth factor was high in the liver, skin and submaxillary gland, which all have detected receptors for the growth factor. Organs, such as lung, heart, spleen, intestine, bone and central nervous system, which lack the receptor, did not retain the growth factor. In tumor bearing mice, the growth factor accumulated in receptor positive tumors, but to a lesser extent than in the liver. This finding will probably prevent the use of epidermal growth factor as a carrier for radionuclides for a therapeutic purpose.

Animals↗

Fine needle aspiration cytology and immunocytochemistry of large cell lymphomas expressing the Ki-1 antigen.

Cytomorphology and immunocytochemistry were used to diagnose two cases of large cell anaplastic lymphomas that expressed the Ki-1 antigen. Smears stained with the May-Grünwald-Giemsa stain showed a cytomorphologic spectrum that varied from immunoblastlike cells to large tumor cells with pleomorphic nuclei. The tumor cells had a distinct basophilic cytoplasm, which often contained vacuoles. Giant cells with wreathlike multilobulated bizarre nuclei were also observed. Immunocytochemistry on a cytocentrifuged specimen showed that the tumor cells were of a T-helper phenotype; all strongly expressed the Ki-1 antigen and receptors for HLA-DR and IL-2.

Adolescent↗

Immunocytochemical detection of estrogen receptors in mammary Paget cells.

Immunocytochemistry was used to analyze the estrogen receptor (ER) content in mammary Paget cells obtained by scraping the nipples of six patients. The Paget cells in the smears were ER positive in four cases and ER negative in two cases. Five of the patients underwent a modified radical mastectomy; histologic study of the excision specimens showed three invasive ductal carcinomas and two intraductal carcinomas. Analysis of the ER status of the three invasive tumors, analyzed both by immunohistochemistry and by the radioligand technique, showed that the ER content in the Paget cells reflected that in the tumor in the breast parenchyma. This finding lends support to the hypothesis that Paget cells originate from an epidermotropic cancer in the parenchyma of the breast.

Adult↗

Maturation asynchrony in leukemic cells. An abnormal combination of normal cell markers.

Multiple monoclonal antibodies and enzyme assays were used to study maturity markers (myelo-peroxidase) and immaturity markers (terminal transferase, HLA-2) in acute myeloid leukemia cells from 35 patients. In 8 of the patients, indications were found of an expression of maturity and immaturity markers on the same cells, here in called maturation asynchrony. It is suggested that the orderly appearance and disappearance of markers during the maturation of normal cells is disordered in malignant cells, and that single markers should be used with caution for the maturation classification of tumors. The simultaneous expression of maturity and immaturity marker by tumor cells could explain also why such cells can be recognized as abnormal even in the absence of tumor specific antigens.

Antibodies, Monoclonal↗

Receptors for epidermal growth factor in human mammary carcinomas and their metastases.

The tumor cell content of the receptor for epidermal growth factor (EGF-R) and estrogen receptor (ER) was analyzed in 36 primary breast carcinomas and their metastatic deposits. Twenty-five percent of the primary tumors and 48 percent of the metastases exhibited measurable levels of the receptor. The frequency of EGF-R positivity was the same for cutaneous and lymph node recurrences. No discrepancy was observed with respect to ER content between primary tumors and their metastases.

Breast Neoplasms↗

Receptors for epidermal growth factor and estrogen as predictors of relapse in patients with mammary carcinoma.

Analysis of the receptors for estradiol and epidermal growth factor was performed in tumors from 225 breast cancer patients. The tumor cell content of both receptors was independent of clinical stage and lymph node status. There was an inverse correlation between the epidermal growth factor receptor and the estradiol receptor. Either the presence of the epidermal growth factor receptor or the lack of the estradiol receptor was related to a high relapse rate. A combination of these two receptors leads to an increased prognostic predictive capacity. Patients whose tumors contain both the estradiol receptor and epidermal growth factor receptor had a relapse rate similar to those whose tumors were estradiol receptor poor, and are thus high risk patients. Patients whose tumors contain the estradiol receptor and lack the epidermal growth factor receptor belong to a good prognosis group.

Carcinoma↗