Wolfgang Kuehn - Profile on Academia.edu (original) (raw)
Papers by Wolfgang Kuehn
Modern Pathology, 2011
Expression of high-risk HPV oncogenes results in a strong overexpression of cellular protein p16 ... more Expression of high-risk HPV oncogenes results in a strong overexpression of cellular protein p16 INK4a . Immunohistochemical staining for p16 INK4a is widely used as diagnostic marker. However, p16 INK4a upregulation was also described as a biomarker of age. Here we analyzed p16 INK4a expression in cervical smears to investigate if patient age may influence p16 INK4a -based cervical cancer diagnosis. p14 ARF was analyzed as a related supportive biomarker. Cervical scrapes were taken and stored in RNAlater. Total RNA was extracted, and cDNA was analyzed for expression of p16 INK4a and p14 ARF relative to b-actin, by real-time reverse transcriptase PCR SYBR-Green I assays. Patient-derived smears referred as HSIL (n ¼ 45) had 6.27-fold higher p16 INK4a mRNA expression than smears of cytologically normal and HPV-negative persons (n ¼ 48). Expression of p14 ARF was 4.87-fold higher. When women with normal diagnoses were stratified for age, a significantly enhanced p16 INK4a (2.88-fold) and p14 ARF (1.9-fold) expression was observed as a consequence of ageing. A significant age-dependent upregulation was also observed in older HSIL patients (2.54-fold). Our study revealed significantly enhanced expression of p16 INK4a /p14 ARF mRNA in cervical scrapes referred to as HSIL compared with normal women. An age-dependent bias has to be considered when quantifying these tumor suppressor genes, with respect to cervical cancer development.
Geburtshilfe und Frauenheilkunde, 1998
Journal of Biomedical Optics, 2014
Journal of Clinical Pathology, 2007
To investigate the role of DNA aneuploidy, particularly in patients with node negative breast can... more To investigate the role of DNA aneuploidy, particularly in patients with node negative breast cancer, in order to identify the different risk profiles within the pool of heterogeneous breast cancers. Methods: Imprint smears from 370 breast carcinomas were Feulgen-stained and measured by DNA image analysis. DNA aneuploidy was graded by the amount of aneuploid cells (DNA content .5c) and highly aneuploid cells (DNA content .9c) in a breast tumour population. These results were correlated to the clinical long-term follow-up. A statistical cutoff value of .10 aneuploid cells (.5c) and of .1 highly aneuploid cell (.9c) was evaluated as significant for disease-free survival (DFS) and overall survival (OS). Results: Subgroups among patients with breast cancer with aneuploid cells below the cutoff value showed a significantly longer DFS and OS than those with aneuploid cells above this value. Patients with node negative breast cancer with .10 aneuploid cells (.5c) and .1 highly aneuploid cell (.9c) showed an unfavourable prognosis similar to patients with node positive breast cancer with ,10 aneuploid cells (.5c) and ,1 highly aneuploid tumour cell (.9c) in DFS and OS. Conclusion: Nuclear DNA content, as an objective marker of tumour aggressiveness, provides prognostic information in patients with both node negative and node positive breast cancer. Based on DNA aneuploidy, the clinically inhomogeneous group of patients with node negative breast cancer can be stratified into low-risk and high-risk subgroups. Therefore, DNA ploidy analysis may identify high-risk patients with lymph node negative breast cancer who might benefit from additional adjuvant therapy.
Journal of the Turkish German Gynecology Association Artemis
Objective: It is proposed that digital colposcopy and telecolposcopy should facilitate the medica... more Objective: It is proposed that digital colposcopy and telecolposcopy should facilitate the medical decision-making process and raise the validity of the diagnosis of cervical carcinoma thereby lowering the incidence and mortality rate of the disease. In order to test this, a digital colposcopy system was developed and clinically evaluated within the framework of a twophase scientific study at the Charité Dysplasia Clinic Berlin. Materials and Methods: In Phase 1 of the evaluation, a total of 315 patients were examined with the digital colposcopy system consisting of a binocular colposcope supplemented with a colour camera and PC, to see whether colposcopic findings can be re-evaluated on the basis of the stored digital images alone, i.e. without the patient being present. Phase 2 was used to test the technical feasibility and reliability of sending colposcopic images by electronic mail. A total of 30 patients from four selected gynecological practices in Berlin had been referred for diagnostic clarification to the Charité Dysplasia Clinic. The digital colposcopic images made there were sent as e-mails to the referring doctors, who in turn evaluated the data transfer. Results: In Phase 1, the primary and secondary examiners were in total agreement in 69% of the cases (κ=0.60). No significant bias in terms of under-or overrating was observed (p<0.05 by McNemar's test). In Phase 2, in 57% (n=17) of the cases, a lack of experience with the new technique led to difficulties with downloading the images. When the practices had become more familiar with the procedure, the incidence of problems fell from 90% (9/10), in the first half of the project, to 40% (8/20) in the second half. In 87% of the cases, the diagnosis of the consulting specialist at the Charité Dysplasia Clinic was comprehensible to the practising physicians. Discussion: Digital colposcopy and telecolposcopy can be effectively used in colposcopy to compensate for the inherent disadvantages of the method, i.e. a high level of inter-and intra-observer variability, inadequate reproducibility and objectivity of colposcopic findings, data storage, data transmission. In practice, there are clear advantages for the diagnosis documentation, follow-up monitoring, further medical education, as well as interdisciplinary communication.
International Journal of Gynecologic Cancer, 2003
Aim: The aim of the present study was to evaluate the characteristics of borderline ovarian tumor... more Aim: The aim of the present study was to evaluate the characteristics of borderline ovarian tumors (BOTs).
Modern Pathology, 2011
Expression of high-risk HPV oncogenes results in a strong overexpression of cellular protein p16 ... more Expression of high-risk HPV oncogenes results in a strong overexpression of cellular protein p16 INK4a . Immunohistochemical staining for p16 INK4a is widely used as diagnostic marker. However, p16 INK4a upregulation was also described as a biomarker of age. Here we analyzed p16 INK4a expression in cervical smears to investigate if patient age may influence p16 INK4a -based cervical cancer diagnosis. p14 ARF was analyzed as a related supportive biomarker. Cervical scrapes were taken and stored in RNAlater. Total RNA was extracted, and cDNA was analyzed for expression of p16 INK4a and p14 ARF relative to b-actin, by real-time reverse transcriptase PCR SYBR-Green I assays. Patient-derived smears referred as HSIL (n ¼ 45) had 6.27-fold higher p16 INK4a mRNA expression than smears of cytologically normal and HPV-negative persons (n ¼ 48). Expression of p14 ARF was 4.87-fold higher. When women with normal diagnoses were stratified for age, a significantly enhanced p16 INK4a (2.88-fold) and p14 ARF (1.9-fold) expression was observed as a consequence of ageing. A significant age-dependent upregulation was also observed in older HSIL patients (2.54-fold). Our study revealed significantly enhanced expression of p16 INK4a /p14 ARF mRNA in cervical scrapes referred to as HSIL compared with normal women. An age-dependent bias has to be considered when quantifying these tumor suppressor genes, with respect to cervical cancer development.
Geburtshilfe und Frauenheilkunde, 1998
Journal of Biomedical Optics, 2014
Journal of Clinical Pathology, 2007
To investigate the role of DNA aneuploidy, particularly in patients with node negative breast can... more To investigate the role of DNA aneuploidy, particularly in patients with node negative breast cancer, in order to identify the different risk profiles within the pool of heterogeneous breast cancers. Methods: Imprint smears from 370 breast carcinomas were Feulgen-stained and measured by DNA image analysis. DNA aneuploidy was graded by the amount of aneuploid cells (DNA content .5c) and highly aneuploid cells (DNA content .9c) in a breast tumour population. These results were correlated to the clinical long-term follow-up. A statistical cutoff value of .10 aneuploid cells (.5c) and of .1 highly aneuploid cell (.9c) was evaluated as significant for disease-free survival (DFS) and overall survival (OS). Results: Subgroups among patients with breast cancer with aneuploid cells below the cutoff value showed a significantly longer DFS and OS than those with aneuploid cells above this value. Patients with node negative breast cancer with .10 aneuploid cells (.5c) and .1 highly aneuploid cell (.9c) showed an unfavourable prognosis similar to patients with node positive breast cancer with ,10 aneuploid cells (.5c) and ,1 highly aneuploid tumour cell (.9c) in DFS and OS. Conclusion: Nuclear DNA content, as an objective marker of tumour aggressiveness, provides prognostic information in patients with both node negative and node positive breast cancer. Based on DNA aneuploidy, the clinically inhomogeneous group of patients with node negative breast cancer can be stratified into low-risk and high-risk subgroups. Therefore, DNA ploidy analysis may identify high-risk patients with lymph node negative breast cancer who might benefit from additional adjuvant therapy.
Journal of the Turkish German Gynecology Association Artemis
Objective: It is proposed that digital colposcopy and telecolposcopy should facilitate the medica... more Objective: It is proposed that digital colposcopy and telecolposcopy should facilitate the medical decision-making process and raise the validity of the diagnosis of cervical carcinoma thereby lowering the incidence and mortality rate of the disease. In order to test this, a digital colposcopy system was developed and clinically evaluated within the framework of a twophase scientific study at the Charité Dysplasia Clinic Berlin. Materials and Methods: In Phase 1 of the evaluation, a total of 315 patients were examined with the digital colposcopy system consisting of a binocular colposcope supplemented with a colour camera and PC, to see whether colposcopic findings can be re-evaluated on the basis of the stored digital images alone, i.e. without the patient being present. Phase 2 was used to test the technical feasibility and reliability of sending colposcopic images by electronic mail. A total of 30 patients from four selected gynecological practices in Berlin had been referred for diagnostic clarification to the Charité Dysplasia Clinic. The digital colposcopic images made there were sent as e-mails to the referring doctors, who in turn evaluated the data transfer. Results: In Phase 1, the primary and secondary examiners were in total agreement in 69% of the cases (κ=0.60). No significant bias in terms of under-or overrating was observed (p<0.05 by McNemar's test). In Phase 2, in 57% (n=17) of the cases, a lack of experience with the new technique led to difficulties with downloading the images. When the practices had become more familiar with the procedure, the incidence of problems fell from 90% (9/10), in the first half of the project, to 40% (8/20) in the second half. In 87% of the cases, the diagnosis of the consulting specialist at the Charité Dysplasia Clinic was comprehensible to the practising physicians. Discussion: Digital colposcopy and telecolposcopy can be effectively used in colposcopy to compensate for the inherent disadvantages of the method, i.e. a high level of inter-and intra-observer variability, inadequate reproducibility and objectivity of colposcopic findings, data storage, data transmission. In practice, there are clear advantages for the diagnosis documentation, follow-up monitoring, further medical education, as well as interdisciplinary communication.
International Journal of Gynecologic Cancer, 2003
Aim: The aim of the present study was to evaluate the characteristics of borderline ovarian tumor... more Aim: The aim of the present study was to evaluate the characteristics of borderline ovarian tumors (BOTs).