Gross cystic disease fluid protein (GCDFP-15) and mammaglobin are both widely used and accepted m... more Gross cystic disease fluid protein (GCDFP-15) and mammaglobin are both widely used and accepted markers for epithelia of breast origin. We aimed to evaluate their relation of expression on parallel whole tissue sections in primary breast cancer by immunohistochemistry and also to correlate it with clinico-pathological parameters including patient survival. Primary breast carcinomas from 165 patients with a mean clinical follow-up of 73 months were immunostained using commercially available antibodies against GCDFP-15 and mammaglobin. An immunoreactive score (IRS) was calculated based on the cytoplasmic staining intensity and the number of cells stained. Cytoplasmic expression of GCDFP-15 and mammaglobin was observed in 73.3% and 72.1% of invasive breast carcinomas respectively. 91.8% of breast cancer cases expressed at least one of both markers. Both markers strongly correlated with each other and were significantly associated with lower tumour grading. Additionally, GCDFP-15 negati...
In the present study we examined prognostic value of immunohistochemical estimation of topoisomer... more In the present study we examined prognostic value of immunohistochemical estimation of topoisomerase 1A (TOP 1A) and HER-2/neu expression in ovarian cancers treated with platinum-based drugs but not with topotecan and the relation between expression of these proteins on the one hand and intensity of proliferation (Ki67) on the other. The analyses were performed on 73 samples of ovarian carcinoma originating from 43 first-look laparotomies (FLL) and, in 30 cases, from secondary cytoreductions (SCR)(after chemotherapy) from the same patients. In paraffin sections immunohistochemical reactions were performed using antibodies directed to HER-2/neu, TOP 1A and Ki67. Kaplan-Meier's analysis disclosed a shorter overall survival time in cases with augmented expression of TOP 1A at FLL and with higher expression of Ki67 at SCR. A shorter progression-free time was detected in cases with higher proportion of Ki67 positive cells at FLL. No relationship could be disclosed between HER-2/neu e...
Der Wunsch, bei schwierigen Fallen oder folgenschweren diagnostischen Entscheidungen, eine zweite... more Der Wunsch, bei schwierigen Fallen oder folgenschweren diagnostischen Entscheidungen, eine zweite Meinung (second opinion) von einem Fachkollegen einzuholen, ist angesichts der schnellen Wissensentwicklung in der Pathologie verstandlich. Da viele Pathologen als Niedergelassene allein in einer Praxis tatig und damit auf sich gestellt sind, eroffnet die elektronische Ubertragung von Mikroskopbildern ganz neue Wege bei der Beurteilung von Kosiliarfallen. Auf das aufwendige und zu grosen Zeitverlusten fuhrende Verschicken des in Paraffin eingebetteten Materials konnte dann in vielen Fallen verzichtet werden.
Comparative genomic hybridization was used to screen 25 adenocarcinomas and 25 squamous cell carc... more Comparative genomic hybridization was used to screen 25 adenocarcinomas and 25 squamous cell carcinomas of the lung for chromosomal imbalances. DNA copy number decreases common to both entities were observed on chromosomes 1p, 3p, 4q, 5q, 6q, 8p, 9p, 13q, 18q, and 21q. Similarly, DNA gains were observed for chromosomes 5p, 8q, 11q13, 16p, 17q, and 19q. Adenocarcinomas showed more frequently DNA overrepresentations of chromosome 1q and DNA losses on chromosomes 3q, 9q, 10p, and 19, whereas squamous cell carcinomas were characterized by increased overrepresentations of chromosome 3q and 12p as well as deletions of 2q. For the first time, we used a histogram representation and statistical analysis to evaluate the differences between both tumor groups. In particular, the overrepresentation of the chromosomal band 1q23 and the deletion at 9q22 were significantly associated with adenoid differentiation, whereas the DNA loss of chromosomal band 2q36-37 and the overrepresentations at 3q21-2...
Resistance to cis- or carboplatin represents the principal cause of therapeutic failures in ovari... more Resistance to cis- or carboplatin represents the principal cause of therapeutic failures in ovarian carcinoma. The phenomenon of resistance to platinum-based drugs is partly related to expression of metallothionein (MT) and of glutathione S-transferase pi (GST-pi), but opinion on the subject is discordant. Documentation of a negative predictive effect of MT and GST-pi expression for the therapy employing platinum-based drugs would permit to select resistant cases in which other therapeutic approaches could be employed. The present study aimed at examining the relation between intensities of MT and GST-pi expressions in ovarian carcinomas and dynamics of the clinical course in the neoplastic disease in a group of cisplatin-treated patients. The analyses were performed on samples of ovarian carcinoma originating from 43 first-look laparotomies (FLLs) and, in 30 cases, from second-look laparotomies (SLL) from the same patients. Immunohistochemical reactions were performed on paraffin sections of studied tumors, using monoclonal antibodies to MT and GST-pi. The calculations showed that in cases with augmented expression of MT, mortality was higher. On the other hand, augmented expression of GST-pi predisposed to more frequent relapses, deaths and progression of the tumor. Kaplan-Meier analysis showed that a significantly shorter survival time was linked to cases of higher expression of MT at FLL and of higher expression of GST-pi at FLL, whereas a shorter progression-free time was manifested by cases with higher expression of GST-pi at FLL. The performed investigations indicate that augmented expressions of MT at FLL and GST-pi at FLL in ovarian cancer represent an unfavourable predictive factor in cisplatin-treated patients.
We present a rapid and specific procedure that enables one to identify living target cells of pep... more We present a rapid and specific procedure that enables one to identify living target cells of peptide hormones within heterogeneous cell populations by means of morphological demonstration of ligand-receptor binding. This is exemplified using a biotinylated parathyroid hormone (PTH) analogue (biotinyl-b-PTH 1-84) which reacts with avidin-fluorescein (avidin-FITC) as a histochemical marker. The experiments revealed a fine dot-like distribution pattern of binding after 1-5 min of incubation at room temperature, changing to a more clustered pattern after 10 min of incubation. Competition of labeled and unlabeled PTH exhibited lack of staining if unlabeled PTH was applied in excess. The results suggest that the demonstrated binding sites represent specific receptors for PTH on living target cells.
High risk human papillomaviruses (HPVs) are central to the development of cervical cancer and the... more High risk human papillomaviruses (HPVs) are central to the development of cervical cancer and the deregulated expression of high risk HPV oncogenes is a critical event in this process. Here, we find that the cell protein nucleolin binds in a sequence-specific manner to the HPV18 enhancer. The DNA binding activity of nucleolin is primarily S phase specific, much like the transcription of the E6 and E7 oncoproteins of HPV18 in cervical cancer cells. Antisense inactivation of nucleolin blocks E6 and E7 oncogene transcription and selectively decreases HPV18+ cervical cancer cell growth. Furthermore, nucleolin controls the chromatin structure of the HPV18 enhancer. In contrast, HPV16 oncogene transcription and proliferation rates of HPV16+ SiHa cervical cancer cells are independent of nucleolin activity. Moreover, nucleolin expression is altered in HPV18+ precancerous and cancerous tissue from the cervix uteri. Whereas nucleolin was homogeneously distributed in the nuclei of normal epith...
Objective: The aim of the current paper is to analyze the significant changes in fetal autopsy ma... more Objective: The aim of the current paper is to analyze the significant changes in fetal autopsy made by pathologists in a center for perinatal medicine in response to the recent rapid developments in prenatal medicine. Methods: We use our technical equipment (interdisciplinary databank, Intranet, fine instruments, imaging techniques) for prenatal diagnostics and fetal pathology in the Center for Perinatal Medicine at the Charité University Medical Center in Berlin, Germany. Results: Our technical setup has made it possible for us to plan autopsies in such a way that rare malformations in special cases can be documented in sectional planes corresponding to the prenatal sonographic images. Before the postmortem examination the pathologist receives all the prenatal findings obtained for the fetus and is able to examine the prenatal images on a monitor. The final diagnosis in the postmortem report includes the results of modern molecular pathology, clinical-genetic examination of the fet...
Gross cystic disease fluid protein (GCDFP-15) and mammaglobin are both widely used and accepted m... more Gross cystic disease fluid protein (GCDFP-15) and mammaglobin are both widely used and accepted markers for epithelia of breast origin. We aimed to evaluate their relation of expression on parallel whole tissue sections in primary breast cancer by immunohistochemistry and also to correlate it with clinico-pathological parameters including patient survival. Primary breast carcinomas from 165 patients with a mean clinical follow-up of 73 months were immunostained using commercially available antibodies against GCDFP-15 and mammaglobin. An immunoreactive score (IRS) was calculated based on the cytoplasmic staining intensity and the number of cells stained. Cytoplasmic expression of GCDFP-15 and mammaglobin was observed in 73.3% and 72.1% of invasive breast carcinomas respectively. 91.8% of breast cancer cases expressed at least one of both markers. Both markers strongly correlated with each other and were significantly associated with lower tumour grading. Additionally, GCDFP-15 negati...
In the present study we examined prognostic value of immunohistochemical estimation of topoisomer... more In the present study we examined prognostic value of immunohistochemical estimation of topoisomerase 1A (TOP 1A) and HER-2/neu expression in ovarian cancers treated with platinum-based drugs but not with topotecan and the relation between expression of these proteins on the one hand and intensity of proliferation (Ki67) on the other. The analyses were performed on 73 samples of ovarian carcinoma originating from 43 first-look laparotomies (FLL) and, in 30 cases, from secondary cytoreductions (SCR)(after chemotherapy) from the same patients. In paraffin sections immunohistochemical reactions were performed using antibodies directed to HER-2/neu, TOP 1A and Ki67. Kaplan-Meier's analysis disclosed a shorter overall survival time in cases with augmented expression of TOP 1A at FLL and with higher expression of Ki67 at SCR. A shorter progression-free time was detected in cases with higher proportion of Ki67 positive cells at FLL. No relationship could be disclosed between HER-2/neu e...
Der Wunsch, bei schwierigen Fallen oder folgenschweren diagnostischen Entscheidungen, eine zweite... more Der Wunsch, bei schwierigen Fallen oder folgenschweren diagnostischen Entscheidungen, eine zweite Meinung (second opinion) von einem Fachkollegen einzuholen, ist angesichts der schnellen Wissensentwicklung in der Pathologie verstandlich. Da viele Pathologen als Niedergelassene allein in einer Praxis tatig und damit auf sich gestellt sind, eroffnet die elektronische Ubertragung von Mikroskopbildern ganz neue Wege bei der Beurteilung von Kosiliarfallen. Auf das aufwendige und zu grosen Zeitverlusten fuhrende Verschicken des in Paraffin eingebetteten Materials konnte dann in vielen Fallen verzichtet werden.
Comparative genomic hybridization was used to screen 25 adenocarcinomas and 25 squamous cell carc... more Comparative genomic hybridization was used to screen 25 adenocarcinomas and 25 squamous cell carcinomas of the lung for chromosomal imbalances. DNA copy number decreases common to both entities were observed on chromosomes 1p, 3p, 4q, 5q, 6q, 8p, 9p, 13q, 18q, and 21q. Similarly, DNA gains were observed for chromosomes 5p, 8q, 11q13, 16p, 17q, and 19q. Adenocarcinomas showed more frequently DNA overrepresentations of chromosome 1q and DNA losses on chromosomes 3q, 9q, 10p, and 19, whereas squamous cell carcinomas were characterized by increased overrepresentations of chromosome 3q and 12p as well as deletions of 2q. For the first time, we used a histogram representation and statistical analysis to evaluate the differences between both tumor groups. In particular, the overrepresentation of the chromosomal band 1q23 and the deletion at 9q22 were significantly associated with adenoid differentiation, whereas the DNA loss of chromosomal band 2q36-37 and the overrepresentations at 3q21-2...
Resistance to cis- or carboplatin represents the principal cause of therapeutic failures in ovari... more Resistance to cis- or carboplatin represents the principal cause of therapeutic failures in ovarian carcinoma. The phenomenon of resistance to platinum-based drugs is partly related to expression of metallothionein (MT) and of glutathione S-transferase pi (GST-pi), but opinion on the subject is discordant. Documentation of a negative predictive effect of MT and GST-pi expression for the therapy employing platinum-based drugs would permit to select resistant cases in which other therapeutic approaches could be employed. The present study aimed at examining the relation between intensities of MT and GST-pi expressions in ovarian carcinomas and dynamics of the clinical course in the neoplastic disease in a group of cisplatin-treated patients. The analyses were performed on samples of ovarian carcinoma originating from 43 first-look laparotomies (FLLs) and, in 30 cases, from second-look laparotomies (SLL) from the same patients. Immunohistochemical reactions were performed on paraffin sections of studied tumors, using monoclonal antibodies to MT and GST-pi. The calculations showed that in cases with augmented expression of MT, mortality was higher. On the other hand, augmented expression of GST-pi predisposed to more frequent relapses, deaths and progression of the tumor. Kaplan-Meier analysis showed that a significantly shorter survival time was linked to cases of higher expression of MT at FLL and of higher expression of GST-pi at FLL, whereas a shorter progression-free time was manifested by cases with higher expression of GST-pi at FLL. The performed investigations indicate that augmented expressions of MT at FLL and GST-pi at FLL in ovarian cancer represent an unfavourable predictive factor in cisplatin-treated patients.
We present a rapid and specific procedure that enables one to identify living target cells of pep... more We present a rapid and specific procedure that enables one to identify living target cells of peptide hormones within heterogeneous cell populations by means of morphological demonstration of ligand-receptor binding. This is exemplified using a biotinylated parathyroid hormone (PTH) analogue (biotinyl-b-PTH 1-84) which reacts with avidin-fluorescein (avidin-FITC) as a histochemical marker. The experiments revealed a fine dot-like distribution pattern of binding after 1-5 min of incubation at room temperature, changing to a more clustered pattern after 10 min of incubation. Competition of labeled and unlabeled PTH exhibited lack of staining if unlabeled PTH was applied in excess. The results suggest that the demonstrated binding sites represent specific receptors for PTH on living target cells.
High risk human papillomaviruses (HPVs) are central to the development of cervical cancer and the... more High risk human papillomaviruses (HPVs) are central to the development of cervical cancer and the deregulated expression of high risk HPV oncogenes is a critical event in this process. Here, we find that the cell protein nucleolin binds in a sequence-specific manner to the HPV18 enhancer. The DNA binding activity of nucleolin is primarily S phase specific, much like the transcription of the E6 and E7 oncoproteins of HPV18 in cervical cancer cells. Antisense inactivation of nucleolin blocks E6 and E7 oncogene transcription and selectively decreases HPV18+ cervical cancer cell growth. Furthermore, nucleolin controls the chromatin structure of the HPV18 enhancer. In contrast, HPV16 oncogene transcription and proliferation rates of HPV16+ SiHa cervical cancer cells are independent of nucleolin activity. Moreover, nucleolin expression is altered in HPV18+ precancerous and cancerous tissue from the cervix uteri. Whereas nucleolin was homogeneously distributed in the nuclei of normal epith...
Objective: The aim of the current paper is to analyze the significant changes in fetal autopsy ma... more Objective: The aim of the current paper is to analyze the significant changes in fetal autopsy made by pathologists in a center for perinatal medicine in response to the recent rapid developments in prenatal medicine. Methods: We use our technical equipment (interdisciplinary databank, Intranet, fine instruments, imaging techniques) for prenatal diagnostics and fetal pathology in the Center for Perinatal Medicine at the Charité University Medical Center in Berlin, Germany. Results: Our technical setup has made it possible for us to plan autopsies in such a way that rare malformations in special cases can be documented in sectional planes corresponding to the prenatal sonographic images. Before the postmortem examination the pathologist receives all the prenatal findings obtained for the fetus and is able to examine the prenatal images on a monitor. The final diagnosis in the postmortem report includes the results of modern molecular pathology, clinical-genetic examination of the fet...
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Papers by M. Dietel