Biomedical subjects

Alfred Böcking

Publications and source records attributed to Alfred Böcking.

18 recordsLinked to original sources

PubMed2005

Methylation assay for the diagnosis of lung cancer on bronchial aspirates: a cohort study.

PURPOSE: Recent studies have detected aberrant promoter methylation of adenomatous polyposis coli promoter 1 A (APC), cyclin-dependent kinase inhibitor-2A (p16(INK4a)), retinoic acid receptor beta2, and RAS association domain family protein 1 (RASSF1A) in bronchial aspirates and suggested their use as biomarkers for lung cancer diagnostics. The purpose of this study was to validate these candidate marker genes in a retrospective cohort study. EXPERIMENTAL DESIGN: Bronchial aspirates collected from a cohort comprising 247 patients with suspected lung cancer were investigated retrospectively regarding aberrant promoter methylation using a quantitative methylation-specific real-time PCR (QMSP). RESULTS: Eighty-nine patients were diagnosed with primary lung cancer, 102 had benign lung disease, and 56 showed miscellaneous other conditions. A panel consisting of APC, p16(INK4a), and RASSF1A emerged as useful combination. This panel detected aberrant methylation in bronchial aspirates of 22 of 35 (63%) and 21 of 44 (44%) centrally and peripherally located primary lung cancers, respectively. Bronchial aspirates also showed aberrant methylation in 5 of 7 (71%) patients with a recurrent lung cancer and in 8 of 30 (27%) cases without tumor recurrence. In contrast, only 1 of 102 patients with benign lung disease displayed a (false) positive test result. Rarely, aberrant methylation was found in patients with other malignancies (3 of 16). The QMSP assay correctly confirmed lung cancer in 8 of 12 (67%) cases with an ambiguous cytology. Moreover, it disclosed 9 of 26 (35%) of peripheral tumors lacking simultaneous cytologic or histologic diagnosis of malignancy. CONCLUSIONS: Our findings suggest that the QMSP assay could be applied as a reflex test in cases of suspected lung cancer that defy a definite diagnosis by conventional methods. Thus, the assay could be a useful diagnostic adjunct especially regarding peripheral tumors.

Adenomatous Polyposis Coli Protein↗

PubMed2005

Aberrant promoter methylation of p16(INK4a), RARB2 and SEMA3B in bronchial aspirates from patients with suspected lung cancer.

Aberrant promoter methylation of normally unmethylated CpG-islands offers a promising tool for the development of molecular biomarkers. We investigated bronchial aspirates of patients admitted for suspected lung cancer with regard to the prevalence of aberrant methylation of potential marker genes. Applying quantitative methylation specific PCR (QMSP) we analyzed bronchial aspirates from 75 patients with primary lung cancer and 64 bronchial aspirates of patients diagnosed with benign lung disease for promoter methylation of 3 candidate marker genes (p16(INK4a), RARB2 and SEMA3B). Hypermethylation of p16(INK4a) detected 18/75 (24%) cases with primary lung cancer and was present predominantly in squamous cell carcinomas (14/25; 56%). RARB2 QMSP at an assay threshold greater than 30 was found in 42/75 (56%) patients with lung cancer without relation to histological subtype. Patients with benign lung disease showed methylation of p16(INK4a) and a RARB2 QMSP at an assay threshold greater than 30 in 0/64 (0%) and 8/64 (13%) cases, respectively. Combining the 2 methylation markers, p16(INK4a) and RARB2, yielded a sensitivity of 69% and a specificity of 87% for the diagnosis of pulmonary malignancy. In contrast, SEMA3B displayed frequent promoter methylation (around 90%) both in bronchial aspirates of tumor and nontumor cases and thus was not suited as a biomarker. The results of this study indicate that QMSP analysis of p16(INK4a) and RARB2 may aid the diagnosis of primary lung cancer in bronchial aspirates. In particular, detection of p16(INK4a) methylation by QMSP may serve as a highly specific marker of pulmonary squamous cell carcinoma.

Adult↗

PubMed2005

Immunocytochemical identification of carcinomas of unknown primary in serous effusions.

Metastases from carcinomas of unknown primary site (CUP) in serous effusion are a common clinical problem. Immunocytochemistry was applied as an adjunct to the cytological diagnosis of metastatic carcinomas in serous effusions. Subjects of this study were 118 pleural, 53 peritoneal, and 9 pericardial effusions from 180 patients routinely investigated in the Institute of Cytopathology. Specimens were primarily stained according to Papanicolaou (Pap). The avidin-biotin-complex method (ABC) was secondarily applied for the visualization of immunologic reactions. We have used a panel of six monoclonal antibodies (CK 5/6, CK 7, CK 20, CA 125, TTF-1, and cdx 2) so as to identify the primary tumor site of metastatic carcinoma cells in serous effusions. Applying an algorithm of immunocytochemical marker constellations, we were able to correctly diagnose primary tumor sites in 86 of 101 (85.1%) patients with CUP syndromes. The best result was achieved for the identification of metastatic carcinomas of the ovaries (94.7%) and the lungs (88.1%). We established an algorithm comprising six immunocytochemical markers that enabled a correct diagnosis of primary tumor sites in 85.1%. The panel studied could be useful in diagnostic routine for the identification of primary tumors of unknown origin metastatic to the serous membranes.

Adult↗

PubMed2005

Cytologic and DNA-cytometric follow-up of oral leukoplakia after CO2- and Er:YAG-laser assisted ablation: a pilot study.

BACKGROUND AND OBJECTIVES: The aim of the present pilot study was to determine therapeutic responses to Er:YAG- and CO(2)-laser ablation in patients with oral leukoplakia as evaluated by means of exfoliative cytology (EC) and DNA-image-cytometry (DNA-I). STUDY DESIGN/MATERIALS AND METHODS: Ten patients exhibiting a total of 16 lesions affecting a variety of intraoral sites were randomly treated with either (1) an Er:YAG laser (300 mJ/pulse, 10 Hz, defocused mode) (ERL), or (2) an CO(2) laser (4-6 W, 20-50 Hz, focused mode) (CO). Brush (B) and incisional (I) biopsies were obtained from the respective lesions immediately before treatment (B, I) as well as 24-96 weeks postoperatively (B). In cases, in which EC revealed suspicious cells, nuclear DNA-contents were measured using a TV image analysis system. RESULTS: Both treatment approaches resulted in a complete (C) or partial (P) remission of all investigated lesions. In particular, ERL exhibited C(3), P(5), and CO C(5), P(3). However, in the CO group, two of eight lesions showed a recurrence 32-48 weeks following treatment. Among all investigated lesions, both histological and EC/DNA-I diagnosis revealed no sign of malignancy or dysplasia before or following laser assisted ablation. CONCLUSIONS: Within the limits of the present study, it may be concluded that both treatment approaches seem to have limitations to achieve predictable eradication of oral leukoplakia.

Adult↗

PubMed2004

Identification of progressive cervical epithelial cell abnormalities using DNA image cytometry.

BACKGROUND: The objectives of the current study were to compare the capabilities of conventional cervical cytology and of DNA image cytometry (DNA-ICM) in the prediction of progressive or regressive behavior in atypical squamous cells (ASC), low-grade squamous intraepithelial lesions (LSIL), and atypical glandular cells (AGC). METHODS: One hundred ninety-six women with Papanicolaou (Pap) smears that yielded diagnoses of ASC, LSIL, or AGC were included in a prospective cohort study. Slides were classified according to the Bethesda system. DNA-ICM was performed according to the consensus reports of the European Society of Analytical Cellular Pathology. RESULTS: Reference standard verification was available in 108 patients. The rate of DNA aneuploidy in Pap smears increased significantly from cervical intraepithelial neoplasia 1 (CIN1) (54%) and CIN2 (64.3%) to CIN3 or greater (CIN3+) (83.3%) in subsequent biopsies (P < 0.05). Using ASC, LSIL, and AGC as input cytologic diagnoses and >/= CIN2 as the output histologic diagnosis, the positive predictive values (PPVs) for conventional cytology and DNA-ICM were 35.2% and 65.9%, respectively (P < 0.001). The negative predictive value (NPV) of DNA-ICM was 85.0%. When >/= CIN3 was used as the output histologic diagnosis, conventional cytology had a PPV of 22.2%. The PPV and NPV of DNA-ICM were 43.9% and 93.3%, respectively. CONCLUSIONS: The results of the current study confirmed the prognostic validity of DNA image cytometry for differentiation between progressive and regressive lesions in patients with ASC, LSIL, and AGC diagnoses.

Adolescent↗

PubMed2004

Aberrant methylation of the adenomatous polyposis coli promoter 1A in bronchial aspirates from patients with suspected lung cancer.

Promoter hypermethylation is a major mechanism for gene silencing and offers a promising starting point for developing molecular biomarkers. The purpose of our study was to determine aberrant methylation of the adenomatous polyposis coli (APC) gene promoter 1A with respect to its prevalence and quantitative level in bronchial aspirates from patients with suspected lung cancer. Applying quantitative methylation-specific PCR, 155 bronchial aspirates from patients with non-small cell cancer (NSCLC) and small cell cancer (SCLC) of the lung as well as 67 bronchial aspirates from patients diagnosed for nonneoplastic lung disease were examined in a retrospective case-control study. Aberrant APC promoter 1A methylation was seen in 71% of NSCLCs, 38% of SCLCs and 42% of patients with nonneoplastic lung disease, being therefore not specific for the presence of primary lung cancer. In contrast, quantitative analysis showed a significantly higher methylation level of bronchial aspirates from NSCLC as compared to patients without neoplastic lung disease. Introducing a cutoff point that defined high level of APC hypermethylation NSCLC could be discriminated from cases without neoplastic disease with a specificity of 98.5% and a sensitivity of 39%. The data suggest that quantitative analysis of APC hypermethylation may serve as a biomarker of primary lung cancer.

Adenomatous Polyposis Coli Protein↗

PubMed2004

Diagnostic and prognostic use of DNA image cytometry in cervical squamous intraepithelial lesions and invasive carcinoma.

In the fight against cervical malignancy and its precursors, several adjuvant diagnostic methods have been proposed to increase the accuracy of cytologic and histologic diagnoses. Because chromosomal aneuploidy has been accepted as an early key event in tumorigenesis caused by genetic instability, the cytometric equivalent of chromosomal aneuploidy detected by DNA image cytometry (DNA-ICM) may serve as a marker of neoplasia. During the last decade, the appearance of a new generation of hardware with high processing and storage capacities, together with the development of appropriate software, has facilitated the development of high-performance DNA-ICM systems. International consensus on the clinical application of DNA-ICM has been reached. According to the statements of Task Force 8 of the International Consensus Conference on the Fight Against Cervical Cancer, indications for DNA-ICM include the identification of prospectively malignant cells in squamous intraepithelial lesions (SILs) and atypical squamous cells of undetermined significance (ASCUS). The European Society of Analytical Cellular Pathology consensus reports on DNA-ICM have provided standardized technical details on performance, terms, and algorithms for diagnostic data interpretation and quality-assurance procedures. Increasing biologic evidence and clinical data have confirmed the utility of DNA-ICM as an adjuvant method suitable for determining the diagnosis and prognosis of cervical intraepithelial lesions and invasive carcinoma. Patients with ASCUS and low-grade SIL diagnoses that reveal DNA euploidy may return for normal screening intervals, whereas the detection of DNA aneuploidy indicates that these lesions should be removed. Formerly a research tool, today, standardized DNA-ICM has become a useful and low-cost laboratory method to establish objectively and reproducibly an early diagnosis of prospectively progressive cervical intraepithelial lesions at a high-quality level. DNA-ICM may further contribute to the monitoring of treatment in patients with invasive cervical malignancies.

Adult↗

PubMed2004

Interobserver reproducibility of DNA-image-cytometry in ASCUS or higher cervical cytology.

In the present study, the aim has been to investigate the interobserver reproducibility of DNA-image-cytometry (DNA-ICM) applied to routine Pap smears classified as Atypical Squamous Cells of Undetermined Significance (ASCUS) or higher lesions (ASCUS+). 202 Pap smears diagnosed as ASCUS or higher were included in the study. After cytological assessment, smears underwent restaining according to Feulgen. First measurements were performed as routine workup. The second measurements were blinded to the result of the first and consecutively performed. DNA-ICM met the consensus statements of the European Society of Analytical Cellular Pathology (ESACP). Interobserver agreement was assessed by calculating Kappa statistics. The diagnosis of DNA-aneuploidy in the first measurements was confirmed in all cases. Second measurement detected 12 additional cases with aneuploidy. Nine out of these cases were classified as aneuploidy by detection of 9c Exceeding Events (9cEE). In three cases stemline-aneuploidy was disclosed. The overall proportion of observed agreement was 94.1%, kappa=0.87, 95% CI=0.74-0.99. Our study shows a good interobserver reproducibility of DNA-ICM performed on cervical smears with ASCUS or higher lesions. DNA-ICM thus represents a highly reproducible diagnostic procedure.

Adolescent↗

PubMed2004

Diagnostic and prognostic value of Ki67 proliferation fraction in serous effusions.

The Ki67 proliferation rate of mesothelial cells was determined in 20 effusions due to malignant mesotheliomas and in 20 non-neoplastic effusions, to investigate if this marker may be useful to identify neoplastic mesothelioma cells and if there is a correlation between proliferation rate and survival time. Using the ABC-method, effusions were immunostained and the marker Ki67 was evaluated quantitatively. Ki67 proliferation fraction showed rates from 2.3% to 70% in malignant mesothelioma cells and from 1.8% to 25.5% in reactive mesothelial cells. A significant difference was found (p=0.05) between those two groups. Assuming a threshold at 26%, a sensitivity of 25% and specificity of 100% resulted. Yet, due to its low sensitivity this marker seems not to be useful for differential diagnosis. Plotting surviving period against Ki67 proliferation fraction a correlation was observed which was not significant. Long term survivors (>28 month) showed proliferation rates below 3.8%. Unexpectedly a highly significant difference (p=0.001) between Ki67 proliferation rates of mesothelial cells from patients with malignant tumors other than mesothelial origin (7.0% to 25.5%) and mesothelial cells of patients without any malignant disease (1.8% to 16.3%) were observed. Setting a threshold at 10% for identification of a malignant disease, a sensitivity of 77.8% and specificity of 90.9% resulted.

Ascitic Fluid↗

PubMed2003

Earliest detection of oral cancer using non-invasive brush biopsy including DNA-image-cytometry: report on four cases.

OBJECTIVE: We describe four patients presenting early oral cancers, detected cytologically on non-invasive brush biopsies including DNA-image cytometry as an adjunctive method before histology on scalpel biopsies confirmed the evidence of malignancy. METHODS: Brush biopsies were performed and smears thereof investigated cytologically. After Feulgen restaining, DNA-measurements were performed using a DNA-Image-Cytometer. CASE REPORTS: Oral squamous cell carcinomas were diagnosed cytologically in macroscopically suspicious lesions and malignancy confirmed by DNA-cytometry. The initially performed scalpel biopsies did neither supply evidence of oral cancer nor of severe dysplasia. After at least one to 15 months the occurrence of cancer was finally proven histologically on a second scalpel biopsy each (three microinvasive and one in situ carcinoma). CONCLUSION: Non-invasive brush biopsies are a suitable instrument for early cytologic detection of cancer of the mouth. DNA-image-cytometry, as an adjunctive method, can be used to confirm the cytologic diagnosis or suspicion of cancer in patients with doubtful lesions (dysplasias). DNA-aneuploidy is a marker for (prospective) malignancy in smears of the oral cavity, which may detect malignancy months prior to histology. In future this method could be used as a mass screening tool in dentists practice.

Aged↗

PubMed2003

DNA extraction from bronchial aspirates for molecular cytology: which method to take?

OBJECTIVE: To date, there are only few systematic reports on the quality of DNA extracted from routine diagnostic cytologic specimens. It was the aim of the present study to evaluate the ability of 50% ethanol/2% carbowax (Saccomanno fixative) to preserve bronchial secretions with high quality genomic DNA as well as to compare different DNA extraction methods. METHODS: DNA was extracted from 45 bronchial aspirates by four different extraction protocols. Beside DNA yield, DNA quality with regard to purity, integrity, and PCR success rate were investigated. RESULTS: No fragmentation of sample DNA due to the fixative was detected. It was preserved as high molecular weight DNA. DNA yield, purity, and integrity were dependent on the DNA extraction method to some extend. Irrespective of the DNA extraction method the PCR success rate for amplification of beta-globin gene fragments (268, 536, and 989 bp) was 100%. CONCLUSION: A fixative containing 50% ethanol/2% carbowax preserves high quality DNA which is well suited for PCR-based assays regardless of the extraction protocol used. The selection of the DNA extraction protocol has to be adjusted to the circumstances of application.

Adult↗

PubMed2003

Diagnostic value of nucleolar organizer regions (AgNORs) in brush biopsies of suspicious lesions of the oral cavity.

OBJECTIVE: The aim of this retrospective study was to report on the diagnostic accuracy of AgNOR-analysis as an adjunctive diagnostic tool of conventional oral exfoliative cytology taken from suspicious lesions in our clinic. STUDY DESIGN: Cytological diagnoses obtained from brush biopsies of macroscopically suspicious lesions of the oral mucosa from 75 patients (final diagnoses: 53 histologically proven squamous cell carcinomas, 11 leukoplakias and other inflammatory oral lesions) and from 11 patients with normal mucosa as a negative control group were compared with histological and/or clinical follow-ups. Five smears were doubtful and seven suspicious for tumor cells in the cytologic report. Number of AgNOR's were counted in 100 squamous epithelial cell-nuclei per slide after silver-restaining. RESULTS: Sensitivity of our cytological diagnosis alone on oral smears for the detection of squamous carcinomas was 92.5%, specificity 100%, positive predictive value was 100% and negative 84.6%. The best cut-off value of the mean number of AgNOR dots per nucleus distinguishing benign from malignant cells was 4.8. The percentage of nuclei with more than three AgNORs had a cut-off level of 70%. Applying these methods to twelve doubtful or suspicious cytological diagnoses we were able to correctly establish the diagnosis of malignancy in ten cases of histologically proven cancers and to reveal benignity in two histologically proven cases. Thus we achieved a positive and negative predictive value of 100% each. CONCLUSIONS: Smears from brushings of visible oral lesions, if clinically considered as suspicious for cancer, are an easily practicable, non-invasive, painless, safe and accurate screening method for detection of oral cancerous lesions. We conclude that AgNOR-analysis may be a useful adjunct to other methods in routine cytological diagnosis of oral cancer that can help to solve cytologically suspicious or doubtful cases.

Adult↗

PubMed2003

Automatic coregistration, segmentation and classification for multimodal cytopathology.

The paper describes the key component of the Multimodal Cell Analysis approach, a novel cytologic evaluation method for early cancer detection. The approach is based on a repeated staining of a cell smear. The correlation of features and data extracted from different stainings, and related to relocated individual cells, will yield a dramatic increase of diagnostic reliability. The necessary fully automatic preprocessing steps are presented: coregistration of multimodal images, segmentation, and classification of cell nuclei. Both efficiency and robustness of all steps reached at the current stage of research, are high regarding medical image material, and strongly support clinical application.

Autoanalysis↗

PubMed2002

Chronic endophthalmitis mimicking an endothelial immune reaction after penetrating keratoplasty.

We describe a patient with chronic inflammation after combined penetrating keratoplasty and cataract surgery. This condition has been considered an unusual endothelial immune reaction. Cytopathological examination of the aqueous humor showed abundant neutrophil granulocytes, a few macrophages, and sparse lymphocytes. The predominance of neutrophil granulocytes but no macrophages or lymphocytes, as found in cases of an endothelial immune reaction, was interpreted as evidence of chronic endophthalmitis. Cytopathological evaluation of aqueous humor can be a helpful tool for differentiating between an endothelial immune reaction and chronic endophthalmitis after combined PKP and cataract surgery.

Antibody Formation↗

PubMed2002

Primitive neuroectodermal tumor (PNET) in the differential diagnosis of malignant kidney tumors.

Primitive neuroectodermal tumors (PNETs) of the kidney, a rare neoplastic disease of high malignancy with a tendency towards early metastasis, affect young adults (26-30 years) irrespective of the gender. Differential diagnosis from other renal tumors is very important for an effective therapy. Herein, we report on a 24-year-old male patient with a renal tumor consisting of small, round cells, and summarize the diagnostic procedures that establish the diagnosis of PNET. Light microscopy revealed not only areas containing small, round cells forming rosettes and pseudorosettes, but also areas containing spindle cells. Expression of CD 99 in combination with neural markers, such as NSE, was detected by immunohistochemistry, and further evidence of neural differentiation was provided by electron microscopy. Image cytometry revealed a peridiploid DNA-stemline. A reciprocal translocation of the chromosomes 11 and 22 [t(11;22)(q24;q12)] with expression of a EWS/FLI-1 fusion transcript was demonstrated by molecular pathology. Using these methods, the diagnosis of PNET was firmly established, and the tumor was treated by surgical resection and subsequent adjuvant chemotherapy. Eighteen months after therapy, the patient is in excellent health condition without any evidence of tumor recurrence.

Adult↗

PubMed2002

Immune cells in the anterior chamber of patients with immune reactions after penetrating keratoplasty.

PURPOSE: Lymphocytes, monocytes, and macrophages are the predominating immune cells in graft rejection after keratoplasty in animal models. This study focuses on the isolation of immune cells from the anterior chamber of patients with slight, moderate, and severe endothelial immune reactions after penetrating keratoplasty. METHODS: Anterior chamber puncture was performed in five patients with cataract without inflammation and without penetrating keratoplasty (C1), in three patients undergoing penetrating keratoplasty without immune reactions (C2), in four patients undergoing penetrating keratoplasty after complete resolution of endothelial immune reactions (C3), in seven patients undergoing penetrating keratoplasty with slight endothelial immune reactions (IMI), in 10 patients undergoing penetrating keratoplasty with moderate endothelial immune reactions (IM2), and in eight patients undergoing penetrating keratoplasty with severe endothelial immune reactions (IM3). In each patient, approximately 0.1 mL of aqueous humor was examined. Cells in suspension were directly centrifuged on glass slides using a Cytospin centrifuge, stained, and evaluated under the light microscope. RESULTS: Groups C1, C2, and C3 did not contain cells. Immune cells were identified in three of seven patients in IM1, in eight of 10 patients in IM2, and in eight of eight patients in IM3. Predominating cells were macrophages and monocytes followed by lymphocytes. Regarding all patients in IMI, IM2, and IM3, a statistically significant correlation between detected cells and patient age, period between penetrating keratoplasty and anterior chamber puncture, or period between first symptoms and anterior chamber puncture could not be revealed. Granulocytes were found statistically significantly less often in patients with high-risk indications, in patients with a history of immune reactions and under immunosuppression. Lymphocytes were found statistically significantly less often in patients with a history of immune reactions. CONCLUSIONS: The probability to isolate immune cells from the anterior chamber of patients undergoing penetrating keratoplasty correlates with the severity of the endothelial immune reactions. This study is a first step to evaluate how detailed immunologic findings from animal keratoplasty models fit to clinical reality in patients undergoing keratoplasty. In the next step, cells found in the aqueous humor of patients with endothelial immune reactions should be further characterized directly (determination of molecules on the surface of the cells) or indirectly (determination of cytokine levels in the aqueous humor).

Adult↗

PubMed2002

Diagnostic DNA-flow- vs. -image-cytometry in effusion cytology.

AIMS: To determine the sensitivity and specificity of flow- and image-cytometry for the detection of DNA-aneuploidy as a marker for malignant cells in effusions. METHODS: 200 effusions (80 tumor cell-positive, 74 negative and 46 cytologically equivocal) were stained with DAPI-SR for DNA-flow- and with Feulgen-Pararosaniline for -image-cytometry. They were measured using a PAS-flow-cytometer and an AutoCyte-QUIC-DNA-workstation according to the ESACP consensus reports for DNA-flow- and -image-cytometry, respectively [7,23,29,49]. RESULTS: Sensitivity of DNA-aneuploidy for the identification of malignant cells was 32.1% for DNA-flow- and 75.0% for -image-cytometry, specificity of -euploidy in benign cells was 100.0% for both methods. Positive predictive value of DNA-aneuploidy for the identification of malignant cells was 100.0% for both techniques, negative predictive value of DNA-euploidy was 48.6% for DNA-flow- and 72.0% for -image-cytometry. CONCLUSIONS: Searching for DNA-aneuploidy as a diagnostic marker for neoplastic cells in serous effusions image-cytometry revealed superior sensitivity as compared with monoparametric flow cytometry.

Algorithms↗

PubMedDate not supplied

Robust automatic coregistration, segmentation, and classification of cell nuclei in multimodal cytopathological microscopic images.

The paper describes the key component of the Multimodal Cell Analysis approach, a novel cytologic evaluation method for early cancer detection. The approach is based on repeated staining of a cell smear. The correlation of features and data extracted from the different stains, and related to relocated individual cells, may yield a dramatic increase of diagnostic reliability. In order to utilise the technique, fully automatic, adaptive image preprocessing techniques need to be applied, which are described in this article: coregistration of multimodal images, segmentation, and classification of cell nuclei. The presented feasibility study shows both efficiency and robustness of all steps being high regarding medical image material, and it strongly supports clinical application.

Cell Nucleus↗