Expression of syndecan-1 in paired samples of normal and malignant breast tissue from postmenopausal women.

BACKGROUND: The mammary stroma is important for modulating epithelial breast cell response to sex steroid hormones. Proteoglycans, such as syndecan-1, promote the integration of cellular signals. MATERIALS AND METHODS: The immunohistochemical expression of syndecan-1 and of the androgen receptor (AR) was analyzed in paired samples of cancer and adjacent normal tissue from postmenopausal women. RESULTS: Normal and cancer tissue showed dramatic differences in the expression of syndecan-1. In malignant breast stroma, mean values were more than 10-fold higher than in normal tissue (p<0.001). There was also a marked redistribution from the epithelium to the stroma. The expression of AR was on average 2-fold higher in cancerous than in normal tissue (p<0.01). CONCLUSION: Breast cancer patients have very different prognoses. Syndecan-1 and the AR may be new molecular markers relevant to clinical outcome. The redistribution from the epithelium and the dramatic increase of syndecan-1 in cancerous stroma may be related to the natural history of the disease.

Are estrogen receptor content in breast cancer and effects of tamoxifen on sex hormone-binding globulin markers for individual estrogen sensitivity?

Individual women differ with respect to their sensitivity to estrogen and serum levels of sex hormone-binding globulin (SHBG) may reflect the individual response. We found a significant correlation between estrogen receptor (ER) concentrations in breast cancer tissue and SHBG levels during tamoxifen treatment. Estrogen sensitivity may be a general characteristic common to various organs and different between individual women.

Expression of sex steroid receptor subtypes in normal and malignant breast tissue - a pilot study in postmenopausal women.

Female sex steroids are implied in breast cancer development. The estrogen (ER) and progesterone (PR) receptor subtypes may have different roles to modulate the cellular response. Paired samples of cancer and adjacent normal tissue were collected from postmenopausal women at surgery for ductal breast cancer. The expression of ERa, ERss, PRA and PRB was quantified by immunostaining and digitized image analysis. We found ERss to be significantly reduced in breast cancer tissue (35% vs 50%; p?=?0.001) and there was also a decrease of the ERss/ERa ratio. Among women using hormones at the time of diagnosis tumor tissue showed higher values for both PRB and PRA, as compared to women without such treatment. The results extend previous animal data to be valid also in women. There is evidence that loss of ERss expression may relate to estrogen dependent tumor progression. Increased PR expression could possibly relate to breast cancer risk during combined estrogen/progestogen treatment.

Hormone receptor status in breast cancer--a comparison between surgical specimens and fine needle aspiration biopsies.

The present study was performed to evaluate the immunocytochemical analysis (ICA) of oestrogen (ER) and progesterone receptor (PR) in fine needle aspiration (FNA) biopsies from primary breast cancers as compared with the established enzyme immunoassays (ER-EIA and PR-EIA) based on cytosol homogenates from the corresponding resected tumour specimens. A total of 967 primary breast cancers were assessed for ER and PR content by both methods. Correlations between EIA and ICA expressed as percentage of tumour cells with a positive staining were highly significant (P < 0.001) for ER and PR. Staining intensity yielded only limited additional information. The concordance between the two techniques was about 80%. Evaluation of biological parameters by FNA may be useful to decide the optimal treatment for breast cancer patients.

Pre-operative simultaneous stereotactic core biopsy and fine-needle aspiration biopsy in the diagnosis of invasive lobular breast carcinoma.

PURPOSE: To determine the diagnostic value of stereotactic core needle biopsy (SCNB) in comparison to stereotactic fine-needle aspiration biopsy (SFNAB) in patients with invasive lobular carcinoma (ILC). MATERIAL AND METHODS: Twenty-two patients with clinical or mammographic findings suspicious of malignancy underwent surgery where postoperative histopathology showed ILC. Pre-operative attempts of diagnosis were made using SFNAB and SCNB. SFNAB was done with a spinal needle 0.7- or 0.9-mm and SCNB was simultaneously performed with an automated 2.1-mm biopsy gun in all patients. RESULTS: SFNAB was diagnostic of carcinoma in 9 women, showed "probable carcinoma" in 5 and "atypia" in 3. In the remaining 5 women, SFNAB showed no atypia. SCNB diagnosed ILC in 20 patients and showed ILC as well as invasive ductal carcinoma (IDC) in 1. Ductal carcinoma in situ was suggested in the remaining patient. CONCLUSION: SCNB was superior to SFNAB in diagnosing ILC and did not miss any carcinoma, whereas SFNAB was non-diagnostic in 8 cases. SCNB is thus recommended in patients with suspicion of ILC of the breast.

Hamartoma of the breast: surgical treatment and reconstruction. Case report.

Hamartoma of the breast is a rare and usually benign tumour with a variable growth pattern. Slowly increasing breast asymmetry is the most common clinical finding. Smaller hamartomas are often diagnosed on mammography. Simple enucleation and secondary expansion of the breast tissue are often sufficient to restore breast symmetry but sometimes, as in the two cases presented, reconstruction is necessary.

Breast cancer in women over 75 years: is axillary dissection always necessary?

OBJECTIVE: To study how the information gained from axillary dissection in women (75 years old or more) with breast cancer influenced postoperative adjuvant treatment. DESIGN: Retrospective review of casenotes. SETTING: University departments of surgery and oncology, Sweden. SUBJECTS: 166 women (aged 75 years or more) operated on for primary breast cancer between 1980-1989. MAIN OUTCOME MEASURES: Type of operation and postoperative therapy given. RESULTS: In 138/166 (83%) women axillary dissection was done, but in only 21/59 (36%) of these patients did information gained from the procedure influence the postoperative treatment according to the treatment guidelines for breast cancer. None of the 28 patients who did not undergo axillary dissection were subjected to further operations or radiotherapy for axillary nodal recurrence after a mean follow up of 47 months. CONCLUSIONS: Axillary dissection should be reserved for local control of disease and for those patients who preoperatively agree to undergo postoperative irradiation or chemotherapy if metastases are found.

Isoforms of procarboxypeptidase B, (pancreas-specific protein, PASP) in human serum, pancreatic tissue and juice.

Human Pancreas-Specific Protein (PASP) has been described as a useful serum marker for pancreatic graft rejection and acute pancreatitis. By molecular cloning PASP has recently been identified as procarboxypeptidase B (PCPB). By use of SDS-gel electrophoresis and Western blots, PASP isoforms (proteins interacting with PASP-antiserum) have now been explored in serum and pancreatic tissue and juice. In serum from healthy volunteers, six different isoforms could be visualised. Their MW varied as follows: > 100 K, about 100 K, 45 K, 35-40 K (two bands) about 30 K and 16 K. The 45 K band, corresponding to PASP purified from pancreatic tissue, was always the major band. In pancreatic cytosol and pancreatic juice, the major band corresponded to PASP (45 K) but weak bands were also seen at MW of 40, 30 and 16 K. In serum from 15 patients with acute pancreatitis, PASP was highly increased. Bands corresponding to PASP/PCPB as well as carboxypeptidase B (CPB) were seen simultaneously. During recovery PASP in serum was normalised and the CPB band disappeared. During 12 episodes of pancreatic graft rejection, PASP in serum was also increased but no changes of isoforms in serum were detected. However during these episodes isoforms in pancreatic juice changed dramatically. The band corresponding to PASP disappeared or became much weaker and only bands with lower MW were seen. We have thus observed changes in PASP/PCB serum isoforms during episodes of acute pancreatitis but not at graft rejection episodes although the total increase of PASP in serum was of the same magnitude.(ABSTRACT TRUNCATED AT 250 WORDS)

A novel assay for pancreatic cellular damage: IV. Serum concentrations of pancreas-specific protein (PASP) in acute pancreatitis and other abdominal diseases.

Pancreas-specific protein (PASP) was compared with serum amylase in 95 episodes of acute pancreatitis with the diagnoses supported by elevated amylase levels. The etiology was typical for Scandinavian countries, with alcohol as the predominant factor, followed by cholelithiasis. PASP values were clearly raised in all patients, except in three cases found to have high salivary-type amylase levels, and one patient with recurrent alcohol pancreatitis. The rise of PASP levels were in general more pronounced than the corresponding amylase elevations, especially in severe pancreatitis. The elevations were generally parallel for the two analytes, but in 41% of the cases PASP levels remained elevated 2-11 days longer than the corresponding amylase levels. PASP was, however, eliminated from the circulation at a rate comparable to that of amylase. The serum range of PASP for 259 healthy subjects was 15-111 micrograms/L with 95% of the values within 16-98 micrograms/L. The upper reference level was set at 100 micrograms/L. PASP levels were also determined for 291 patients with disorders other than acute pancreatitis. Serum levels in patients with renal insufficiency (n = 12), primary biliary cirrhosis (n = 9), and diabetes mellitus (n = 17) were equal to those in healthy subjects. Eight patients of 173 with acute abdominal disorders and no evidence of pancreatitis had elevated PASP levels as well as 4 patients with prostatic carcinoma (n = 28) and 2 patients with benign prostatic hyperplasia (n = 16). PASP values were low in chronic painful pancreatitis (n = 15) and pancreatic cancer (n = 11).

Pancreas-specific protein. New serum marker for graft rejection in pancreas-transplant recipients.

A radioimmunoassay for a novel human pancreatic protein (pancreas-specific protein, PASP) has been developed. We studied the possibility that serum PASP levels reflect pancreas-graft rejections in human pancreas-transplant recipients. Ten patients subjected to combined pancreas-kidney transplantation and 4 patients subjected to pancreas transplantation alone were studied. Twelve kidney recipients served as control subjects. On several occasions, PASP levels were elevated at kidney rejections in patients with combined pancreas-kidney grafts and then decreased after antirejection therapy, although no other indications for concomitant pancreas-graft rejection were at hand. In the recipients of pancreas grafts alone, PASP levels increased before or at the same time as graft rejections were indicated by current methods. In two cases of chronic graft rejection, PASP rose to high levels long before hyperglycemia occurred. In the control group of kidney-graft recipients, PASP levels were stable and were not affected by high serum creatinine levels, kidney-rejection episodes, or antirejection therapy. This study indicates that PASP may be a good serum marker for pancreas-graft rejection.

A novel assay for pancreatic cellular damage: III. Use of a pancreas-specific protein as a marker of pancreatic graft dysfunction in humans.

Pancreas-specific protein (PASP) is a recently isolated and partially characterized major protein in the human pancreas. It has not been described previously. Serum levels of PASP and amylase were analyzed in 21 patients subjected to combined renal and segmental pancreatic transplantation with both organs obtained from the same donor and in eight kidney transplant patients. In the pancreas transplant patients, PASP and amylase levels were elevated in episodes of graft pancreatitis. With chronic graft rejection, PASP rose to high levels long before other indications. In episodes of renal rejection, the levels of PASP, but not always of amylase, were elevated on several occasions. They decreased after antirejection therapy. This may indicate accompanying pancreatic graft rejection. PASP and amylase levels were stable in kidney transplant patients and were not affected by serum creatinine levels, renal rejection, or antirejection therapy. The results support earlier observations that renal rejection in combined pancreas and renal transplant patients may or may not be accompanied by a rejection process in the pancreatic graft. PASP may be the means by which to tell when the pancreatic graft is involved.

The estrogen binding protein in human pancreas: concentrations in subcellular fractions of normal pancreatic tissue, in duodenal juice during pancreatic stimulation and in peripheral serum in normal and pathological conditions.

The steroid binding properties of the human pancreatic estrogen binding protein (hEBP) in cytosol were studied by equilibrium dialysis. A high ligand specificity of the protein was revealed. hEBP in cytosol binds unconjugated steroid estrogens with a medium affinity (Kd = 10(-7) M) but does not bind conjugated estrogens or unconjugated androgens, gestagens, glucocorticoids or cholesterol. Quantitation of hEBP by radioimmunoassay in subcellular fractions of human pancreatic tissue indicated that the protein is translocated into different subcellular compartments. Duodenal juice taken from patients following stimulation of pancreatic secretion by food ingestion (Lund's test) showed high hEBP concentrations, and the levels of hEBP changed concomitantly with the levels of pancreatic isoamylase, indicating that hEBP secretion was stimulated by food ingestion. The levels of hEBP in peripheral serum from healthy subjects showed no sex difference, but were positively correlated to age. Highly elevated (10-20-fold) hEBP levels were found in serum from patients with acute pancreatitis, while normal serum hEBP values were found in other abdominal diseases. It is speculated that hEBP might have a specific role in the transport of estrogens from the peripheral circulation via the pancreas to the duodenum. The elevated hEBP levels in patients with acute pancreatitis indicate that this protein may be used as a marker of cellular damage in the pancreas.

A novel serum assay for pancreatic cellular damage. II. High tissue specificity of a pancreatic protein.

A previously unknown major protein in human pancreatic cytosol has been purified and partly characterized. The protein, designated pancreas specific protein (PASP), has a molecular weight of 44,500 and a pI of 6.9. A two-dimensional gel separation technique revealed the protein to be specific for normal pancreatic tissue. Antibodies against PASP were raised in rabbits and a radioimmunoassay was developed for the quantitation of this protein. The following concentrations of PASP (mg/kg wet weight) were found in human tissues: normal pancreas 100-1,000; pancreatic carcinoma 0.1-20; prostate 0.5-5; and 13 other tissues less than 0.5. The levels of PASP in peripheral serum were less than 0.1 mg/L in normal subjects, 0.7-3 mg/L in cases of acute pancreatitis, and less than 0.1 mg/L in cases of pancreatic carcinoma, prostatic diseases, and other abdominal diseases investigated. The high tissue specificity and the specific elevation of serum PASP levels in acute pancreatitis may indicate a use of this protein as a marker of this pancreatic condition.

Novel assay for pancreatic cellular damage: 1. Characterization of protein profiles in human pancreatic cytosol and purification and characterization of a pancreatic specific protein.

The protein patterns of cytosols from normal human pancreas and pancreatic carcinoma were studied by a two-dimensional separation technique using high-performance liquid chromatography followed by isoelectric focusing on polyacrylamide gels and visualization of the focused proteins by Coomassie Blue staining. Almost identical protein patterns were obtained for 20 different specimens from normal pancreas, whereas quite different protein patterns were found in 12 samples of pancreatic carcinoma. A major protein in normal pancreatic cytosol, not identical to any macromolecule previously tested as a marker for pancreatic function, was selected for further studies. The protein was not found in specimens of pancreatic carcinoma. It was purified by a single step chromatofocusing procedure, focused at pH 6.9, and moved as one single band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent molecular weight of 44,500 daltons. Total amino acid analysis revealed a high concentration of glutamic acid, leucine, and lysine. The purified protein had no amylase activity or lipase immunoactivity. It constituted approximately 2% of the total normal pancreatic cytosol protein. Later immunological studies have shown the protein to be highly specific for normal human pancreas, indicating a possible future use as a marker for pancreatic cell damage.

Metabolism of estrone sulfate by normal human pancreatic tissue in vitro.

Homogenates of normal pancreatic tissue obtained from five female and nine male subjects transformed (3H)estrone sulfate into (3H)estrone and (3H)estradiol-17 beta in vitro. No other unconjugated (3H)metabolites were found. The rates of transformation were comparable to those previously demonstrated in mammary carcinoma and greatly exceeded those found in endocrinologically unrelated pectoralis and abdominal muscle. The results may provide additional indications for a possible association between estrogens and pancreatic function.

Analysis of an estrogen binding macromolecule in human pancreas by radioimmunoassay.

A radioimmunoassay for quantitation of the human pancreatic estrogen binding protein (hEBP) was developed using polyclonal rabbit hEBP antiserum and iodinated purified hEBP. Parallel dose-response curves were obtained when serial dilutions of human serum and of cytosols obtained from human pancreas, prostate and colon were analyzed simultaneously with serial dilutions of purified hEBP standard. Very high levels of hEBP (500-1000 mg/kg wet weight) were found in normal pancreas. High as well as medium levels were found in pancreatic carcinoma tissue and medium values (0.1-1 mg/kg wet weight) in prostate, colon and ovarian tissue. Other tissues and serum from healthy volunteers showed low values, usually below 0.1 mg/kg. When serial dilutions of rat pancreatic cytosol were analyzed in the hEBP assay, [125I]hEBP was displaced by the rat preparation, but the dose-response curves were not parallel to the standard curves, indicating similarity but non-identity between the estrogen binding proteins in human and in rat pancreas.

Further characterization of the estrogen binding macromolecule in human pancreas.

The estrogen binding protein in human pancreas has been purified from pancreatic cytosol by chromatography on Concanavalin-A-Sepharose and hydroxyl-apatite followed by ion-exchange chromatography carried out using a fast-protein liquid chromatography apparatus (FPLC). The purified protein, still able to bind labelled [3H]estradiol, appeared as one single band corresponding to 31 K in SDS-gel electrophoresis. Total amino acid analysis revealed high levels of histidine, glutamic acid and leucine. The capacity of the purified protein to bind estrogens could be increased more than 4-fold by addition of a cytosolic factor, probably being a small peptide, that is present in crude cytosol, but lost during the purification procedure. The iodinated protein does not bind to DNA-cellulose or phosphocellulose, and shows no similarities to estrogen receptor proteins.