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Biomedical subjects

A Schauer

Publications and source records attributed to A Schauer.

At least 199 records · Page 11Linked to original sources

Relevance of ploidy related parameters for prognosis in malignant fibrous histiocytomas.

Ploidy associated parameters were determined in 161 malignant fibrous histiocytomas (MFH) by DNA image cytometry. The rate of euploid cases in MFH with histopathological grade I was 42%, grade II 16% and grade III 6%. Univariate analyses showed that cases with a low percentage of diploid cells (< 40%) and cases with high rates of aneuploid cells between 4c and 8c (> 9%), octaploid cells (> 0%) and 16-ploid cells (> 0%), high 2.5c (> 60%) and 5c (> 16%) exceeding rates and cases with high DNA indices of the first (> 1.08) and the second (> 3.78) peak had significantly reduced survival rates. Multivariate analyses with Cox regression demonstrated that in addition to grade, only the percentage of aneuploid cells between 4c and 8c, the 5c exceeding rate and the DNA index of the first peak had independent prognostic impact. It was concluded that besides ploidy status and grading, ploidy associated parameters are suited for prediction of survival in MFH.

Adolescent↗

Helicobacter pylori-induced hyperproliferation: relevance for gastric cancer development in connection with mutagenic factors.

AIMS: Current data on Helicobacter pylori induced regenerative hyperproliferation of the antral gastric mucosa and significance in cancer development are still under discussion and investigation. An improved method for evaluation of the regeneratory process in antral mucosa is introduced and compared with the conventional method used for determination of proliferating cells in perpendicular sections of the gastric mucosa. METHODS: Using a combination of immunohistochemistry and PAS-staining the expression of Ki-67 (MiB1)-proliferation associated antigen was analyzed in 50 Helicobacter pylori (Hp) positive and 35 negative biopsies of the gastric antrum. PAS-staining was performed to identify the proliferative zone of the antral gastric glands. The degree of inflammation was evaluated by grades on routinely H & E-stained slides. RESULTS: Proliferative activity is significantly increased in Hp-positive cases (p = 0.00095) compared to negative ones. By using the conventionally applied proliferation index, every nucleus has to be counted and the proliferation zone is identified by at least one positive stained nucleus. The method presented here seems to be easier because the proliferative zone is clearly identified by PAS staining of neutral glycoproteins characteristic for the proliferation zone of antral glands. The density of labeled nuclei is determined and is expressed as a proliferation factor. This factor gives more distinct values, is easier to evaluate and shows a better correlation with the helicobacter status and the degree of inflammation. These results are discussed in relation to the data from the literature and with a view to other relevant factors in the course of carcinogenesis, such as growth factors, mainly EGF, p53 mutation and role of apoptosis, genetic instability and local production of oxidants. CONCLUSION: Helicobacter pylori induces an increase of regenerative proliferation activity. Under these conditions the chance of mutation is increased and time for DNA repair reduced. This could be at least a part of multiple step carcinogenesis. The newly introduced combination of staining procedures (PAS/MiBI) allows a more differentiated evaluation of the proliferation zone and its widening. This method can be more easily handled in follow-up studies than the method using perpendicular sections because in this method heavy irregularities of gland pattern induced by accompanying inflammatory processes considerably hinder evaluation.

Cell Division↗

Analysis of the DNA mismatch repair proteins expression in malignant melanomas.

The importance of properly functioning DNA mismatch repair has been shown in several tumour types both hereditary and sporadic, but not yet in malignant melanomas. The aim of this study was to examine the expression of DNA mismatch repair genes (MLH1, MSH2, PMS1 and PMS2) in primary melanomas and to define their possible prognostic impact in 106 primary melanomas. MLH1 was found in 64 and MSH2 in 61 out of 106 melanomas. PMS1 and PMS2 proteins were present in 69 and 67 tumours, respectively. Loss of the expression of DNA mismatch repair proteins correlated with the increase of Clark levels. Cox regression analysis demonstrated some prognostic significance for PMS1 (forward p = 0.0018 and backward selections p = 0.0277), MLH1 (only forward selection p = 0.0081) and MSH2 (only backward selection p = 0.0115).

Adaptor Proteins, Signal Transducing↗

[Morphologic and biochemical aspects of prostaglandin-induced cervix ripening].

For examination by electron microscopy tissue samples were taken from the posterior lip of the cervix of 8 patients having a termination of pregnancy at 9-12th week gestation and 16 patients of comparable gestational age who had an intracervical application of either 2 ml 5% tylose or 50 micrograms sulprostone-tylose gel 8 hours before biopsy. The efficacy of cervical priming was demonstrated objectively by tonometric studies. In addition, collagenase and protease activities were determined in the cervical tissue extracts of the different treatment groups. For identification of typical collagen fragments SDS-polyacrylamide-gel-electrophoresis were carried out on the acetic acid soluble extracts. The local application of sulprostone gel induced a marked multifocal loosening of the collagenous framework; there was no evidence for leucocyte infiltration or necrosis caused by the prostaglandin (PG) pretreatment. In the areas of disorganized collagen fibres cervical fibroblasts seemed to be activated characterized by fine granular loosening of the cytoplasma, dilated cisternae of rough endoplasmatic reticulum, vacuolized enlarged mitochondria and an increased number of cytoplasmatic vesicles close to the cell surface. Collagenase and protease activities were found in all extracts of the different treatment groups, however, PG-application led to no significant increase in enzymatic activities. There was no evidence for the presence of typical collagen cleavage products in the SDS-electrophoresis. Contradictory to the hitherto published literature enzymatic collagen degradation does not play an essential role in PG-induced cervical ripening.

Abortifacient Agents↗

Immunohistochemical localization of CD44 variants 5 and 6 in human gastric mucosa and gastric cancer.

The aim of this study was to compare the distribution of CD44 variants 5 and 6 in normal mucosa and gastric cancer and to determine their relationship with histoclinical Parameters of the disease. Experimental material included 112 paraffin blocks of various human gastric carcinomas. Both variants of CD44 were detected immunohistochemically with primary antibodies deriving from Bender Med. Systems. In normal gastric mucosa positive reactions with both antibodies were observed in surface epithelium, parietal cells, myocytes and vascular endothelia. They were also found in intestinal enterocytes, esophageal epithelium and myoepithelial. Additional reactivity with antibodies against variant 6 was observed in Paneth cells. In gastric cancer, variants 5 and 6 were demonstrated in 91% and 64% of cases respectively, without significant correlation with the tumor type. The occurrence of variant 6 correlated positively with tumor size (p = 0.081) and negatively with histological grading (p = 0.093). The relationship with metastases was insignificant.

Carrier Proteins↗

Significance of P-53 antigen in malignant melanomas and naevi of the head and neck area.

DO-7 antibody against p-53 antigen was applied for investigation of melanomas of facial skin (25 cases), oral cavity (17 cases), eye (18 cases) and naevi (25 cases). The p-53 index value (% of p-53 positive cells) was correlated with the thickness of the tumour, the presence of metastases and survival time. The difference in p-53 index between naevi and melanomas was statistically significant (p < < 0.01). A significant correlation was found between the p-53 index value and the thickness of the tumour, the presence of metastases and follow-up for patients with skin, oral and ocular melanomas. The possible diagnostic and prognostic significance of p-53 antigen in melanomas and naevi of the head and neck area is discussed.

Antibodies↗

CD-44: a marker of metastases of head and neck melanomas.

Specimens of 38 melanomas of the oral cavity and facial skin and 23 lymph nodes with melanoma metastases were stained immunohistochemically for the presence of variants 5, 6, 7 and 8 of CD-44 antigen. A positive reaction was observed only for variant 7-8 in primary melanomas as well as in lymph nodes with metastases from melanoma. The CD-44 score (percentage of CD-44 positive cells chi intensity of reaction) correlated with metastatic behaviour of tumours and was greater in metastatic lymph nodes than in primary tumours.

Adult↗

Prognostic relevance of Ki-67 antigen and c-myc oncoprotein in malignant fibrous histocytoma.

47 cases of malignant fibrous histiocytoma were stained immunohistochemically for the presence of Ki-67 antigen and c-myc oncoprotein. Percentage of Ki-67 and c-myc positive cells correlated with each other and with grade of tumour, mitotic index, cellularity and survival time of patients, but not with the extent of necrosis. Differences of mean values of Ki-67 index between grade I and grade II tumours as well as between grade II and grade III tumours were highly statistically significant. All 3 parameters connected with c-myc expression (index, intensity and score) differed significantly between grade I and grade II tumours but not between grade II and grade III MFH. The possible differential role of Ki-67 antigen and c-myc oncoprotein for improvement of grading is discussed.

Adult↗

Differential expression of cerbB3 in naevi and malignant melanomas.

28 naevi, 43 malignant melanomas and 16 lymph nodes with melanoma metastases were stained immunohistochemically for the expression of cerbB3 oncoprotein. using antibody RTJ1. Positive reaction was found in 60% of naevi and in 25% of melanoma cases. The difference in frequency of the reaction occurrence between naevi and melanomas was statistically highly significant (p = 0.0017). In naevi, the percentage of cerbB3 positive cells (56.5%) was also significantly higher (p = 0.021) as compared with that of melanomas (37%). The cerbB3 positive cells were found only in cases without metastases. Positive reaction was also observed in 4 out of 16 investigated lymph nodes with melanoma metastases. The role of cerbB in the development of melanoma is discussed.

Antibodies, Monoclonal↗

Antigen Ki-67 and c-myc oncogene as related to histoclinical parameters in pigmented skin lesions.

121 cases of cutaneous melanomas, 82 lymph nodes with melanoma metastases and 62 naevi were stained immunohistochemically for presence of Ki-67 antigen and c-myc oncogene. A significant correlation between expression of investigated markers, and survival time as well as presence of metastases, in cutaneous melanomas was found (p < 0.05). The role of Ki-67 antigen for differential diagnosis between naevi and melanomas is also demonstrated.

Adult↗

P-53 positivity and high proliferative index: factors of bad prognosis in malignant fibrous histiocytomas.

57 cases of malignant fibrous histiocytomas (MFH) were examined, immunohistochemically for the presence of p-53-tumour suppressor gene with monoclonal antibody DO-7 (Dako) and for the presence of Ki-67 antigen using monoclonal antibody MIB-1 (Dianova). The statistical relationship between the overexpression of p-53 and grading parameters (mitoses, cellularity, necrosis) and expression of Ki-67 antigen as well as survival time, was determined. The presence of p-53 antigen was found in 29.8% of grade II and grade III tumours, but not in MFH of grade I. The p-53 positive cases demonstrated a significantly higher mitotic index (p < 0.05), higher Ki-67 index (p < 0.05) and shorter survival time (p < 0.05) in comparison to p-53 negative cases. Differences concerning cellularity and extent of necrosis, between p-53 positive and p-53 negative tumours were not found (p > 0.05). The prognostic role of p-53 overexpression in MFH is discussed.

Adult↗

Flow-cytometric analysis of the DNA content in paraffin-embedded tissue and in fresh tumour samples obtained from renal cell carcinoma: comparison of DNA ploidy using ethidium bromide and mithramycin.

With the help of the deparaffination technique described by Heldly, it has become possible to conduct large-scale flow-cytometric (FCM) studies, including retrospective DNA analysis of renal cell carcinoma (RCC). The quality of these histograms, however, has to be comparable to the quality of the analyses from fresh tumour tissue. The present study compares the application of FCM on fresh tumour tissue from RCC with paraffin-embedded archive material, thus for the first time, the same combination of stains (ethidium bromide/mithramycin) was used for both materials. From a total of 44 tumours, 125 histograms were obtained from fresh tumour tissue. Aneuploidy was found in 78 (62.4%) of the DNA analyses (coefficient of variation, CV = 5.5%). These 78 aneuploid histograms were compared with 228 sections from the archive material which had been deparaffined and stained. This involved, a deparaffinising period of twelve hours as well the application of pepsin and protease, which was necessary to obtain high-quality histograms (CV = 6.0%). Retrospectively, a total of 58 histograms from 36 cases were available for comparison. Of the archive material, 23/36 tumours were classified as aneuploid; thus new stem cell lines could be detected retrospectively in 63.8% of the cases. The comparison of DNA indices (DI) in the two series produced no significant differences, and the comparison of the mean values for the CV-5.5% for native material histograms and 6.0% for archive material histograms-was not statistically significant. The detritus part in the archive histograms revealed a mean value of 6.3% for native histograms the mean value was 13.4%. These differences were also not significant. These results show that, using the staining combination ethidium bromide/mithramycin, the quality of the histograms obtained with archive material is equal to the quality of the histograms obtained from fresh tumour material. Furthermore, when taking into consideration the clonal heterogeneity of RCC, it is possible to use retrospective analysis to detect aneuploidy with a high degree of certainty and accuracy.

Carcinoma, Renal Cell↗

Prognostic significance of p105 (c-erbB-2 HER2/neu) serum levels in patients with ovarian cancer.

BACKGROUND: Elevated serum levels of the oncoprotein p105 (c-erbB-2, HER2/neu) have been found in patients with ovarian cancer, but its role in this disease has not been clearly established. MATERIALS AND METHODS: The authors studied the relationship between p105 serum levels, various tumor parameters, and survival in 57 patients with newly diagnosed, untreated ovarian cancer. Serum specimens were obtained at the time of initial surgery, and p105 levels were determined using the human neu quantitative ELISA assay. RESULTS: Elevated p105 serum levels were correlated with a poor prognosis since patients with low p105 levels had a better survival than patients with high p105 levels (P = 0.02). This result was confirmed in stage III patients (n = 29; P = 0.08). p105 serum levels were not related to tumor stage, grade, histologic findings or serum CA 125 levels. CONCLUSIONS: Our results suggest that ovarian cancer patients with elevated p105 serum levels may have a poor clinical outcome.

Adolescent↗

Mib-1 evaluated proliferative activity in ovarian cancer with respect to prognostic significance.

In the present study, tumor tissue of 251 patients with ovarian cancer was immunohistochemically analysed for proliferative activity using the monoclonal antibody mib-1 and the analyse system CAS 200. The rate of the growth fraction varied from 0% to 71% mib-1 positive tumor cells with a median of 17%. There was a strongly significant association between proliferative activity and the degree of histological differentiation (p = 0.0005), whereas there was no significant correlation with tumor stage and histological subtypes. Using the median as the cut-off point, patients with higher proliferating tumors (> or = 17%) had a statistically significant worse prognosis (p = 0.0431). Especially in the group of patients with grade 1 and grade 2 tumors, measurement of the proliferative activity is of help for prediction of the postoperative survival time of patients (p = 0.0336), suggesting that measurement of the growth fraction estimated by mib-1 reflects more closely the degree of tumor differentiation. However, multivariate analyses cannot confirm these results.

Adolescent↗

Serum levels of the c-erbB-2 (HER2/neu) encoded oncoprotein fragment p105 in normal pregnancies.

The c-erbB-2 encoded oncoprotein p185 is overexpressed in fetal epithelial cells, in the placenta, and in several human carcinomas. Elevated serum levels of the 105 kD extracellular part are found in cancer patients and in pregnancy. Our purpose was to examine whether there is a characteristic development of p105 serum levels in the course of normal pregnancy. Using ELISA, we measured the p105 serum concentrations in nonpregnant women, women with normal pregnancy in the 1st, 2nd, and 3rd trimester and pueperas. Compared to nonpregnant women, we found a significant decrease in p105 in the 1st and 2nd trimester, followed by a significant increase in the 3rd trimester. Post partum serum values returned to the levels found in nonpregnant women. The clinical judgment of female p105 serum values requires comparison with the normal range of random samples, and the consideration of pregnancy and the age of gestation as in vivo influencing factors.

Enzyme-Linked Immunosorbent Assay↗

Differential expression of apoptosis associated genes bax and bcl-2 in ovarian cancer.

The prognostic value of various molecular markers, which adequately account for the tumor biology and disease behaviour of ovarian cancer, is still unclear. Recent studies have focused on the role of genes regulating the balance between proliferation and cellular suicide, apoptosis. In the present study, tumor tissue from 215 patients with ovarian cancer was immunohistochemically analysed for Bax- and Bcl-2-expression. There was an association between Bcl-2-expression (30%) and factors of favourable prognosis. In contrast, Bax-expression (47%) was related to bad clinical outcome, especially in cases without concomitant Bcl-2-expression. In patients with Bcl-2-positive/Bax-negative tumors, overall survival was significantly longer (p = 0.0379) than in patients with Bcl-2- and Bax-negative tumors. Respectively, expression of Bax without Bcl-2-expression was correlated with bad clinical outcome (p = 0.033). The difference in overall survival was most striking (p = 0.0007) between patients with Bax-positive/Bcl-2-negative and Bcl-2-positive/Bax-negative tumors. This could also be demonstrated for the various subgroups of different tumor grade and stage. It may be speculated, that alteration of the Bax/Bcl-2-balance may influence the clinical course by deregulation of programmed cell death and altered sensitivity to chemotherapy.

Adenocarcinoma, Clear Cell↗

Differential expression of growth arrest, DNA damage genes and tumour suppressor gene p53 in naevi and malignant melanomas.

Twenty nine benign naevi and 59 melanomas of different Clark level and locations were stained immunohistochemically for the presence of p53 and 3 members of Growth Arrest. DNA Damage inducible family: GADD 34, GADD 45 and GADD 153. All naevi were p53 negative and highly GADD positive. Differences in the expression of all 3 GADD proteins between naevi and melanomas were highly significant (p = 0.0001). The expression of p53 increased and the expression of GADD proteins decreased with the Clark level of melanoma thickness. The survival time of patients correlated negatively with p53 positivity and positively with GADD 45 and 153 expression. Prognostic significance for GADD 34 was not found. Our conclusion is that GADD proteins play an important role in the malignant transformation of naevus to melanoma and GADD 45 and GADD 153 proteins can influence patient survival.

Adolescent↗