Biomedical subjects

Klaus Friese

Publications and source records attributed to Klaus Friese.

62 records · Page 4Linked to original sources

PubMedDate not supplied

Expression of sialyl lewis X, sialyl Lewis A, E-cadherin and cathepsin-D in human breast cancer: immunohistochemical analysis in mammary carcinoma in situ, invasive carcinomas and their lymph node metastasis.

OBJECTIVE: Breast cancer cells can invade and generate metastasis via either lymphatic or blood vessels. Sialyl Lewis X (SLeX) and Sialyl Lewis a (SLea) are carbohydrate molecules that mediate the adhesion between tumor cells and the endothelium. These antigens are not expressed on normal breast tissue. Overexpression of SLeX and SLea is combined with poor prognosis and malignant relapse. E-cadherin mediates tumor cell-tumor cell adhesion. Partial or complete loss of E-cadherin expression has also been found to correlate with poor prognosis in breast cancer patients. Another factor involved in metastasis is Cathepsin-D, a lysosomalprotease. Cathepsin-D plays a role in cell proliferation and inhibition of tumor cell adhesion. In this study, we analysed the combined expression of SLeX, SLea, Cathepsin-D and E-cadherin in breast carcinoma in situ, invasive carcinomas without metastasis and invasive carcinomas with lymph node metastasis. MATERIALS AND METHODS: Slides of paraffin-embedded tissue of carcinoma in situ (8 DCIS, 2 CLIS), invasive carcinomas without metastasis (9 ductal, 1 lobular) and carcinomas (7 ductal, 2 lobular, 1 mucinous) with their lymph node metastasis (10 cases) were used. Breast cancer tissue was fixed and incubated with monoclonal antibodies against SLex (IgM) and SLea (IgM), Cathepsin-D (IgG) and E-cadherin (IgG). Staining reaction was performed with the ABC reagent. The intensity of immunohistochemical reaction on digital images of the slides was analyzed using a computer-aided detection system. RESULTS: We found a weak expression of both Sialyl Lewis antigens, a strong expression of E-cadherin and a moderate expression of Cathepsin-D in carcinoma in situ. The expression of both Sialyl Lewis antigens, E-cadherin and Cathepsin-D was moderate in invasive carcinomas without metastases. However, a strong expression of both Sialyl Lewis antigens and a very weak expression of E-cadherin was detected in primary carcinoma with lymph node metastases. The expression of Cathepsin-D was moderate in this tissue. E-cadherin expression was elevated whereas SLeX and Cathepsin-D expression was reduced in lymph node metastases compared to the primary tumor. CONCLUSION: Combined analysis of tumor antigens involved in adhesion of breast cancer cells showed a negative correlation between Sialyl Lewis antigens and E-cadherin as the risk of metastasis progresses. Furthermore, there were significant differences of expression of the Sialyl Lewis antigens, E-cadherin and Cathepsin-D in primary breast cancer cells and their metastases. Evaluation of a panel of markers involved in cell adhesion could be a useful method for defining the metastatic risk in breast cancer patients.

Breast Neoplasms↗

PubMedDate not supplied

Parathyroid hormone-related peptide (PTH-rp) in normal, hyperplastic and malignant endometrial tissue: an immunohistochemical analysis.

UNLABELLED: Parathyroid hormone-related peptide (PTH-rp) is a peptide initially purified from tumors with hypercalcemia, which is also produced in human endometrium. The aim of this study was to determine the frequency and tissue distribution of PTH-rp in normal, hyperplastic and malignant endometrium. MATERIALS AND METHODS: Paraffin-fixed endometrial tissue was obtained randomly from women in the proliferative (n = 4), early secretory (n =5) and late secretory (n = 5) phases, as well as glandular-cystic hyperplasia (n = 5), adenomatous hyperplasia (AH) grade I (n = 5), grade II (n = 4), grade III (n = 4) and endometrioid adenocarcinoma grade I (n = 5). The PTH-rp expression was evaluated by immunohistochemical procedure. A semiquantitative analysis and a statistical evaluation was performed. RESULTS: Immunohistochemical reaction with PTH-rp was primarily observed in glandular and luminal epithelial cells. Stromal and myometrial cells also expressed PTH-rp. The expression of PTH-rp in glands was significantly higher during the late secretory than in the proliferative phase. The highest expression was observed during AH grade III, while the lowest reaction was detected in the proliferative phase and adenocarcinoma. DISCUSSION: PTH-rp was expressed in normal, hyperplastic and malignant endometrial tissue. A cyclical expression of PTH-rp in normal glandular epithelium was observed, being more prominent in the late secretory phase. AH grade I to III also expressed PTH-rp with higher immunostaining than adenocarcinoma. Since AH grade III can be considered as a precursor of endometrial cancer, PTH-rp could be a marker of cell transformation. Endometrioid adenocarcinoma expressed the lowest PTH-rp immunostaining, indicating either a lower expression or a reflection of an increased PTH-rp shedding of malignant transformed endometrium. Further studies are required to establish the usefuleness of PTM-rp as a marker in different endometrial pathologies.

Endometrial Hyperplasia↗

PubMedDate not supplied

Measurement of glycodelin A in fluids of benign ovarian cysts, borderline tumours and malignant ovarian cancer.

BACKGROUND: Glycodelin A levels in fluids of benign ovarian cysts, borderline tumours and ovarian cancer, as well as serum-levels of glycodelin A, were analysed in patients with benign and malignant ovarian tumours. The aim of the study was to investigate if the level of glycodelin A in body fluids of patients with malignant ovarian tumours could be a marker for the disease. Additionally, immunohistochemical investigations of glycodelin A expression in tissue of ovarian cancer were performed. MATERIALS AND METHODS: A total of 158 samples of fluids from benign ovarian cysts, borderline tumours and ovarian cancer were collected during surgery in the Department of Obstetrics and Gynaecology at the University of Rostock, Germany. Additionally, 69 samples of serum from patients with benign ovarian cysts and ovarian cancer on the day before surgery were collected. An ELISA for determination of glycodelin A was used. Immunohistochemical detection of glycodelin A expression was performed on ovarian cancer tissue from 38 patients. RESULTS: Malignant cystic fluids showed higher glycodelin A values (mean: 1814.4 ng/ml) compared to fluids of benign ovarian cysts (mean: 784.4 ng/ml). The results of glycodelin A determination were compared using the Mann- Whitney U-test for comparison of the means. There was a statistically significant difference between benign ovarian cysts and malignant ovarian cancer for the fluid (p <0.001). In addition, serum samples of malignant ovarian tumours also showed significantly higher glycodelin A values compared to serum levels of benign tumours (p<0.001). Immunohistochemical staining on ovarian cancer tissue showed a glycodelin A expression in 25-30% of the carcinoma cells. CONCLUSION: High levels of glycodelin A were found in cystic fluids of ovarian cancer. In addition, we also found higher levels of glycodelin A in the serum of patients with ovarian cancer compared to the serum of patients with benign ovarian cysts. Furthermore, ovarian cancer tissues showed intense staining with a glycodelin A antibody. Further investigations are necessary to show if glycodelin A quantification could help to diagnose ovarian cancer.

Body Fluids↗

PubMedDate not supplied

Expression of Her2/neu, steroid receptors (ER and PR), Ki67 and p53 in invasive mammary ductal carcinoma associated with ductal carcinoma In Situ (DCIS) Versus invasive breast cancer alone.

AIMS: (a) To assess the expression patterns of HER2/neu, steroid receptors (ER and PR), Ki67 and p53 in invasive ductal cancer (IDC) and IDC associated with carcinoma in situ (IDC/DCIS) and (b) to determine if there is a differential expression of these molecular markers between IDC and IDC/DCIS. MATERIALS AND METHODS: Paraffin-fixed breast cancer samples, diagnosed with only one histological invasive tumor (IDC (n=130), and IDC/DCIS (n=36) were analyzed by immunohistochemical means. The non-parametric Mann-Whitney and chi2 tests were used to evaluate any statistical differences between different groups. Significance was assumed at p<0.05. RESULTS: A significant increase of the tumor grading was observed between IDC and IDC/DCIS (p<0.05). Her2/neu amplification was demonstrated in 49.6% of IDC compared to 31% of IDC/DCIS (p<0.05). ER expression showed no statistical differences between IDC and IDC/DCIS. The PR expression was demonstrated in 71% of IDC with significantly lower intensity than IDC/DCIS (p<0.05). The Ki67 expression was significantly higher (p<0.05) in IDC cases (64%) versus IDC/DCIS (49.7%). No differences were observed between IDC and IDC/DCIS for p53 expression. CONCLUSION: We demonstrated significantly different expression patterns of Her2/neu, PR and Ki67 in IDC versus IDC/DCIS. Since these molecular markers play important roles in carcinogenesis and tumor progression, IDC/DCIS could be an important subtype of mammary invasive ductal cancer. Differences in expression of the evaluated markers might suggest a higher malignant potential of invasive carcinomas alone. The lower expression of Her2/neu and Ki67 in IDC/DCIS could implicate a less malignant behavior compared to a differentiated IDC. Additionally, these results might suggest that DCIS might be a malignant preform and the interaction with neoplastic tissue could result in an aggressive type of invasive tumor.

Breast Neoplasms↗

PubMedDate not supplied

TGF-alpha, c-erbB-2 expression and neoangiogenesis in vulvar squamous cell carcinoma.

BACKGROUND: TGF-alpha and c-erbB-2 are important mediators of tumor neoangiogenesis linked to the epidermal growth factor receptor. Thus, we analyzed TGF-alpha c-erbB-2 and tumor neoangiogenesis in vulvar carcinoma and determined their prognostic significance. PATIENTS AND METHODS: Seventy-five carcinomas were evaluated for histological parameters. Tumors were stained immunohistologically for TGF-alpha, c-erbB-2 and factor VIII antigen. Results were analyzed statistically by chi2-test, Kaplan-Meier survival curves and log-rank-test. RESULTS: Sixty-five % of the carcinomas were positive for TGF-alpha in >50% of the tumor cells. C-erbB-2 overexpression occurred in 47% of the tumors, but there was frequently a high cytoplasmatic staining. Twenty-nine % showed high microvessel densitiy. These tumors were more likely to have vascular space involvement (p=0.02). In carcinomas with TGF-alpha expression in >50% of the tumor cells, microvessel density was increased (p=0.05). Overall and disease-free survival tended to be reduced for tumors with high TGF-alpha expression and microvessel density, but differences were not significant. CONCLUSION: Tumor neoangiogenesis is an important event in vulvar carcinogenesis which is related to the expression of growth factors.

Female↗

PubMedDate not supplied

P53 expression in vulvar carcinoma, vulvar intraepithelial neoplasia, squamous cell hyperplasia and lichen sclerosus.

BACKGROUND: p53 inactivation due to oncogenic viral proteins or mutations is an important molecular mechanism in carcinogenesis, which has also been demonstrated for vulvar carcinoma. To evaluate p53 changes in vulvar carcinogenesis, we analyzed p53 expression in vulvar carcinoma, vulvar intraepithelial neoplasia (VIN), lichen sclerosus (LS) and squamous cell hyperplasia (SH). PATIENTS AND METHODS: Seventy-three carcinomas, 141 cases of VIN, 55 biopsies of LS with 8 associated to carcinoma, 57 cases of SH with 14 associated to carcinoma and 10 cases without neoplastic changes were stained immunohistologically for p53. The pattern, intensity and number of stained cells were analyzed. Results were compared to p53 expression in vulvar epithelium without neoplastic changes and analyzed statistically by chi2-test. RESULTS: Normal vulvar epithelium showed low p53 staining in the basal epithelial layers. Forty % of LS and SH not associated to carcinoma showed immunohistological signs of p53 mutation, while cases associated with carcinoma did so in 90%. In VIN, p53 was predominantly overexpressed in the differentiated subtype. Sixty-seven % of the carcinomas showed immunohistological changes of p53 expression. Tumors with low p53 expression were significantly associated with patients younger than 50 years (p<0.01) and basaloid or condylomatous tumor type (p<0.015). There were three different patterns of p53 staining, which were significantly correlated with tumor type (p<0.01). CONCLUSION: p53 mutations are present in typical keratinizing carcinomas, precursor lesions and disorders with elevated risk for vulvar cancer. Thus, p53 mutation seems to occur early in vulvar carcinogenesis and may become a useful marker, especially in lesions with increased risk of carcinoma.

Carcinoma in Situ↗

PubMedDate not supplied

Expression of glycodelin in human breast cancer: immunohistochemical analysis in mammary carcinoma in situ, invasive carcinomas and their lymph node metastases.

OBJECTIVE: Glycodelin is a 28 kDa glycoprotein, previously known as placental protein 14 (PP 14). Glycodelin displays immunosuppressive and contraceptive properties. It also suppresses the cytolytic capacity of human natural killer (NK) cells in vitro and inhibits binding of sperm cells to the zona pellucida (the outer membrane of the oocyte). Glycodelin is expressed in normal glandular epithelium of the endometrium as well as in endometrial, ovarian and cervical carcinoma cells. Glycodelin is also expressed in normal and malignant glandular cells outside the reproductive tract, like hidroadenoma, parabronchial glands, sweat glands and pancreatic cystadenoma. Recently, glycodelin was demonstrated to be expressed in normal and cancerous human breast tissue. MATERIALS AND METHODS: Paraffin-embedded slides of carcinoma in situ (8 DCIS, 2 CLIS), invasive carcinomas without lymph node metastases (9 invasive duct carcinomas, 1 invasive lobular carcinoma) and invasive carcinomas (7 invasive duct carcinomas, 2 invasive lobular carcinomas, 1 mucinous carcinoma) with corresponding lymph node metastases were used. Immunohistochemical staining reaction was used to detect glycodelin expression in the different types of carcinoma in situ, in invasive carcinoma of the human breast and in metastatic carcinoma in axillary lymph nodes. RESULTS: Glycodelin expression was found in all cases of carcinoma in situ (10/10). In the group of invasive carcinoma of the breast (ductal and lobular carcinoma) without lymph node metastases, expression of glycodelin was demonstrated in 9 cases (9/10), of whom 3 cases showed a strong and 6 cases a mediate to weak expression of glycodelin. Only 1 case was negative. In the group of invasive breast cancer with axillary lymph node metastases, in 5 cases (4 ductal and 1 lobular carcinoma) there was no expression of glycodelin, either in the primary tumour tissue, or in the metastatic infiltration of the axillary lymph nodes (5/10). In only one case (invasive ductal carcinoma) was there a strong expression of glycodelin in the primary tumour and a weak expression in the metastasis in axillary lymph node. In 4 other cases (2 ductal, 1 lobular and 1 mucinous), there was a weak staining in primary breast cancer cells and no expression in the metastatic lymph node. CONCLUSION: These results demonstrate that invasive breast carcinomas without axillary lymph node metastases (better prognosis) are more likely to express glycodelin. In contrast, the cases of breast cancer with metastatic infiltration of the axillary lymph nodes showed no (or weak) expression of glycodelin (worse prognosis). On the basis of these results, we speculate that glycodelin expression could be used as a prognostic marker for breast cancer. This has to be confirmed in larger studies.

Breast Neoplasms↗

PubMedDate not supplied

Human chorionic gonadotropin (hCG) as inhibitior of E-selectin-mediated cell adhesion.

OBJECTIVE: Human chorionic gonadotropin (hCG) is a placental glycoprotein hormone of clinical importance. It is secreted into maternal circulation, amniotic fluid, urine and is also found in the serum and urine of patients with malignant trophoblastic diseases. Depending on the source, we detected a remarkable expression of sialyl Lewisx on this protein. Sialyl Lewis' is known as a minimal ligand recognized by selectins, which are involved in cell adhesion processes in inflammatory and metastatic diseases. In this context, the purpose of the study was to explore the ability of hCG to serve as a selectin antagonist. MATERIALS AND METHODS: We purified hCG from human amniotic fluid, serum and urine of pregnant women and from supernatants of the trophoblastic tumour cell lines Jeg3 and BeWo by immunoadsorption chromatography. The proteins were functionally tested for a specific blockade of the E-selectin-mediated cell adhesion in vitro. The efficiencies of hCG from different origins were compared. RESULTS: We found that hCG isolated from serum, amniotic fluid and supernatant of the cell line Jeg3 were strong inhibitors with at least 10(3)-fold higher potency compared to the monovalent tetrasaccharide sialyl Lewisx. As expected from the carbohydrate expression, hCG isolated from the urine of pregnant women, but even from the supernatant of BeWo cells, showed no inhibitory effect. CONCLUSION: hCG is an effective selectin antagonist. This fact suggests that hCG may play a role in preventing leukocyte adhesion on the foetal syncytiotrophoblast or the metastatic activity of trophoblastic tumour cells.

Cell Adhesion↗