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H Kreipe

Publications and source records attributed to H Kreipe.

At least 19 recordsLinked to original sources
PubMed2006

[Hepatocellular adenoma. Malignancy potential and differentiation from hepatocellular carcinoma].

In contrast to hepatocellular carcinoma (HCC), very few molecular pathological studies have been carried out on hepatocellular adenoma (HCA). Particularly from the surgical point of view, based on views passed on verbally and in the literature of the 1970s and 1980s, a possible degeneration of the HCA provides grounds for operating. Published cases of transitions from HCA into HCC were evaluated on the basis of today's morphological standards. A comparison was made between the patterns of new molecular pathological studies of HCA, above all the work of our own groups, and those of HCC. The results speak against the suggestion that a typical solitary HCA in pre-menopausal women is a precursor lesion of HCC. After a critical review of the literature, only one casuistic case of a transition of HCA to HCC under a hormone therapy, which is no longer practiced today, remained. A limitation of particular HCA in genetic and metabolic diseases, children, adult males, adenomatosis, and HCA-like tumors with known risk factors of HCC would seem pragmatically meaningful. With classic HCA, however, the oncological indication for surgery does not apply. A prerequisite is a histological clarification, if necessary with the support of molecular pathological methods.

Adenoma↗
PubMed2006

[Improvement of breast cancer grading in punch biopsies: grading with the Ki-67 marker].

The grading of invasive breast cancers according to Bloom and Richardson (Nottingham modification) provides one of the most important prognostic factors in addition to size and the status of the lymph nodes. Diagnostic reproducibility has been problematic in daily practice as the required criteria for selection and extent of the grading area are frequently not present in the punch biopsies.A total of 346 cases were retrospectively used to compare routine grading from surgical preparations with an equivalently small sample from punch biopsies. In addition, a modified grading of these small samples was developed with Ki-67 immunochemistry and the measurement of core size. In the case of modified grading, 1-3 points were given for Ki-67 and average maximum core diameter. Tubule development was evaluated with 1 or 2 points. A comparison for recurrence free survival and total survival showed significant prognostic differences between 3-5 points (low risk) and 6-8 points (high risk) in uni- and multivariate analyses. The evaluation criteria for Nottingham-Bloom-Richardson grading in a small tissue sample, such as that from a punch biopsy, can hardly be fulfilled. In our series, prognostic value was only found for nodal negative cases. After modification using objective parameters such as nuclear size measurement and Ki-67 proliferation index, a small tissue sample can prove to be of significant prognostic value for nodal negative as well as nodal positive cases.

Biomarkers, Tumor↗
PubMed2005

Compartment-specific quantitative gene expression analysis after laser microdissection from archival renal allograft biopsies.

BACKGROUND: Various immunological and non-immunological pathomechanisms are responsible for the cellular damage in renal allografts. Since the kidney is an anatomically complex organ with functional and morphological heterogeneous compartments (interstitium, tubuli, vessels, glomeruli), the local response to injury maybe variable, therefore, the identification of local pathomechanisms is important. AIM: To elucidate any discrepancies in quantitative mRNA expression profiles between a total specimen analysis and a cell-specific evaluation after laser microdissection. METHODS: Real-time RT-PCR was performed for complement component C3 and heme oxygenase-1 (HO-1) genes compared to the housekeeping gene beta-actin using whole section RNA extracted from formalin-fixed and paraffin-embedded archival material of 16 explanted, rejected renal allografts. Ten non-transplant nephrectomies served as controls. For five cases from each group, five different compartments of the organs (interstitium, proximal tubuli, distal tubuli, vessels, glomeruli) were microdissected and quantitative analysis for C3 and HO-1 was performed identically. RESULTS: Whole section mRNA expression analysis: the data showed a constant expression of the housekeeping gene beta-actin, a 7-fold increased expression of C3 and a 3-fold decreased expression of HO-1 in the allograft group as compared to the control group. mRNA expression results from microdissected compartments: in the control group, C3 and HO-1 expression could only be detected in the proximal tubuli of all cases whereas all five compartments analyzed from the rejecting kidneys showed expression of the two genes. In the allografts, expression levels of the investigated genes varied considerably not only among the different compartments but between individual cases as well. CONCLUSION: Laser microdissection combined with real-time RT-PCR is a feasible approach for retrospective quantitative gene expression analysis in formalin-fixed and paraffin-embedded renal allograft specimens. As shown for C3 and HO-1, cell-specific expression patterns ofpathogenetically relevant genes vary considerably between individual cases. A close correlation of morphology and cell-specific gene expression analysis will contribute to the elucidation of the complex pathogenesis of chronic renal allograft nephropathy.

Actins↗
PubMed2004

[Epigenetic changes in breast cancer shown by aberrant promoter methylation].

The aberrant methylation of cytosine residues in the promoter region of growth-regulatory genes is now recognized as an important inactivation mechanism in addition to deletion and mutation in the development and progression of cancer. Principally all pathways regulating proliferation and differentiation, which are perturbed in cancer cells, can be affected. In breast cancer epigenetic inactivation is a frequent and early event displaying great quantitative gene-specific differences during progression. The occurrence of specific aberrant methylation patterns is associated with the histological grade and subtype of mammary carcinoma biopsies.

Breast Neoplasms↗
PubMed2003

Aberrant methylation and impaired expression of the p15(INK4b) cell cycle regulatory gene in chronic myelomonocytic leukemia (CMML).

The important cell cycle regulatory gene p15(INK4b) has been shown to be inactivated in acute myeloid leukemia and myelodysplastic syndrome. Little is known about the expression and epigenetic modification of this gene in chronic myelomonocytic leukemia (CMML) that belongs to the myelodysplastic/myeloproliferative disorders (MDS/MPD) with a high proportion of blastic transformation. Analysis of bone marrow trephines in a series of 33 CMML cases showed an aberrant p15(INK4b) gene methylation in up to 58% of cases. Methylation was analyzed employing different methylation-specific PCR and genomic sequencing protocols. It turned out to be spread over a broad area of the 5' region and exhibited substantial heterogeneity between cases and even in individual patients. The degree of aberrant methylation was correlated with a reduced mRNA as well as reduced protein expression, and was associated with a higher expression of DNA methyltransferase DNMT 3A. We conclude that aberrant gene methylation is a frequent event in CMML that might contribute to the pathogenesis of this MDS/MPD.

Bone Marrow↗
PubMed2003

Telomere shortening of epithelial cells characterises the adenoma-carcinoma transition of human colorectal cancer.

BACKGROUND: and aims: Chromosomal instability is one of the most consistent markers of sporadic colorectal cancer in humans. There is growing evidence that telomere shortening is one of the mechanisms leading to chromosomal instability and cancer initiation. METHODS: To test this hypothesis, the telomere length of colorectal epithelial cells and cells from connective tissue was determined at the adenoma-carcinoma transition at the cellular level by quantitative fluorescence in situ hybridisation. RESULTS: Our study showed that the telomere fluorescence intensity of epithelial cells was significantly weaker at the earliest morphologically definable stage of carcinoma-high grade dysplasia with minimal invasive growth-compared with the surrounding adenoma. In contrast, cells from connective tissue had a similar telomere signal intensity at the carcinoma stage compared with the adenoma, and in turn cells from connective tissue had overall significantly stronger telomere fluorescence signals compared with epithelial cells. CONCLUSIONS: These results demonstrate that short telomeres of epithelial cells characterise the adenoma-carcinoma transition during human colorectal carcinogenesis, suggesting that carcinomas arise from cells with critical short telomeres within the adenoma. Since the adenoma-carcinoma transition in colorectal cancer is characterised by an increase in chromosomal instability and anaphase bridges, our data support the hypothesis that short telomeres initiate colorectal cancer by induction of chromosomal instability.

Adenoma↗
PubMed2002

[Histopathology of leukaemic non-Hodgkin's lymphoma in bone marrow].

Staging biopsies of the bone marrow in lymphoma patients are among the most important indications and therefore of substantial practical importance. Occasionally it is the only organ infiltrated, and therefore a bone marrow biopsy is the prime diagnostic choice in cases of leukemic lymphomas. A synoptical diagnostic approach relying on immunophenotypic as well as on molecular biological criteria aside from histomorphology (cytomorphology), is of utmost importance for the subtyping of malignant lymphomas. This too can be done reliably on bone marrow biopsies, as comparative studies have yielded a concordance rate of more than 90% with lymphoma typing on corresponding lymph nodes. Cytology and the pattern of infiltrates, (i.e. diffuse, interstitial, nodular peritrabecular and intrasinusoidal), in combination with immunological phenotyping are the mainstays for subtyping, giving clear-cut decisions in most cases of small B-cell lymphoma, mantle zone as well as marginal cell and follicular lymphomas and hairy cell leukemia. Among the blastic variants the most important are the lymphoblastic lymphomas of either B- or T-cell type which have to be discerned from AML and the so-called blastoid mantle cell lymphomas. T-cell lymphomas are rare compared to B-cell lymphomas. Among the rarely seen T-cell neoplasias the lymphoma of large granular lymphocytes is the dominating lymphoma, which in most cases can only be diagnosed reliably by molecular biological means, followed by T-CLL, Sezary's syndrome and hepatosplenic chi delta lymphoma.

Biopsy↗
PubMed2002

[The development of myelofibrosis in prefibrotic cIMF. An investigation of the progression by sequential bone marrow biopsies in 38 patients].

Overt myelofibrosis in bone marrow biopsies as a diagnostic postulate in cIMF has been discarded only recently by the WHO. Therefore, only a few studies have been performed on the evolution of myelofibrosis in "prefibrotic" cIMF by means of sequential bone marrow biopsies. We carried out this study on 38 patients, split up into two groups, A and B according to treatment modalities, to evaluate the dynamics and frequency of myelofibrosis in both groups. Our results indicate a step-wise development of myelofibrosis from a "prefibrotic" to a "classical" cIMF, as 75-80% of the respective patients in both groups progressed to myelofibrosis. However, this evolution seems to be heterogeneous and unpredictable in individual patients, since myelofibrosis could be seen as early as less than 2 years after diagnosis in 12/38 (31.6%) patients, whereas 3 patients remained "prefibrotic" even after up to 6 years of follow-up.

Biopsy, Needle↗
PubMed2001

Real-time PCR analysis of DNA and RNA extracted from formalin-fixed and paraffin-embedded biopsies.

The archives of departments of pathology represent a unique source of morphologically defined biopsies derived from normal and pathologically altered tissues for which extensive clinical data are available. The exact quantification of nucleic acids in these biopsies offers a promising extension of current methodology to study the pathogenesis of many different diseases. The development of real-time PCR technology has greatly facilitated the realization of nucleic acid quantification. Now it is feasible to analyze large series of samples for the exact quantification of nucleic acids even if the number of target molecules is small and the amount of material available for analysis is limiting. This review focuses on our own experiences concerning the extraction of nucleic acids from fixed and embedded biopsies using both conventional approaches and laser-assisted microdissection and the subsequent application of real-time PCR methods for quantification of mRNA transcripts, gene copy number, and the methylation status. We provide a number of protocols to assist in the application of these techniques.

Biopsy↗
PubMed2001

Correlation of MRI and CT findings with histopathology in hepatic angiomyolipoma.

Hepatic angiomyolipomas are rare and often mimic other liver tumors. The aim of our study was to describe the CT and MRI findings and to correlate imaging features with histopathology. The CT and/or MR images were available for retrospective analysis in seven patients. Patients had non-enhanced as well as enhanced CT (n = 6) or MRI (n = 4) before and after administration of Gd-DTPA (n = 2) or MnDPDP, a liver specific contrast agent, (n = 3). In three patients CT and MRI did not detect fat, and in two patients the angiomyolipomas were also histopathologically devoid of fat. Vascularity ranged from hypervascular (n = 4) with arteriovenous shunts (n = 1) to equal (n = 1) or less (n = 2) postcontrast enhancement compared with the normal liver parenchyma. No uptake of the liver specific contrast agent, MnDPDP, was observed (n = 3). Predominantly, CT and MRI did not include angiomyolipoma in the differential diagnosis, and the initial histopathological evaluation was inconclusive in more than half the cases. Hepatic angiomyolipomas frequently manifest as solitary well-circumscribed heterogeneous masses in patients with no underlying liver disease or elevation of serum tumor markers. If present, the demonstration of intratumoral fat is helpful in the diagnosis of angiomyolipoma. The final diagnosis can be obtained by immunohistochemistry.

Adult↗
PubMed2001

Demonstration of light chain restricted clonal B-lymphoid infiltrates in archival bone marrow trephines by quantitative real-time polymerase chain reaction.

Assessment of clonality either by demonstrating light chain restriction or showing monoclonal immunoglobulin gene rearrangement is a valuable and indispensable adjunct to diagnosis in hematopathology. The study of light chain restriction by immunohistochemistry on archival material is hampered by a very low sensitivity especially regarding low grade lymphomas of B cell origin. DNA rearrangement studies of the immunoglobulin locus do improve sensitivity markedly but for lymphomas of follicle center origin they are prone to false negative results due to hypermutations. Therefore we developed a new clonality assay based on the quantification of immunoglobulin light chain transcripts using real-time polymerase chain reaction technology, which is also suitable for the analysis of archival bone marrow trephines. We tested the reproducibility and sensitivity of this approach by comparatively analyzing a series of bone marrow trephines with multiple myeloma (n = 26), reactive lymphoid hyperplasia (n = 37), and focal infiltration by low grade B cell lymphoma (n = 29). We could raise the detection rate of clonality from an average of 17% by immunohistochemistry and 66% as assessed by polymerase chain reaction rearrangement studies to 83% by this new technique. Despite false negative results due to light chain hypermutation in some cases, the detection rate of clonality could be improved even for B cell lymphomas of follicle center origin (follicular lymphoma or marginal zone lymphoma) thus making this novel approach a valuable additional tool for the hematopathologist.

B-Lymphocytes↗
PubMed2001

Diagnostic impact of fluorescence in situ hybridization in the differentiation of hepatocellular adenoma and well-differentiated hepatocellular carcinoma.

Histopathological differentiation between hepatocellular adenoma and well differentiated hepatocellular carcinoma (HCC) may be a difficult task in small biopsies and occasionally in resected tumor specimens. Whether the analysis of chromosome aberrations can contribute to a more precise discrimination has not been analyzed systematically up to now. Therefore, fluorescence in situ hybridization was applied to 28 cases of adenoma and well differentiated carcinoma, using centromeric probes for chromosomes 1, 6, 7, 8, and X. None of 14 adenomas revealed an aberrant count in the analyses performed. By contrast, 13/14 carcinomas demonstrated aberrations for 2-5 chromosomes/case. Chromosome 1 was aberrant in 8/12 cases informative for this probe (67%), chromosomes 6 and 7 were aberrant in 9/14 cases (64%), chromosome 8 was aberrant in 11/14 cases (79%), and chromosome X in 7/14 cases (50%). Taking results for chromosomes 1 and 8 together, 13/14 HCC revealed aberrations for at least one of these chromosomes. Probes for 6, 7, and X revealed no additional aberrant cases.Thus, FISH for chromosomes 1 and 8, extended by probes for chromosomes 6, 7 and X, represents a promising approach toward a more accurate differentiation between hepatocellular adenoma and carcinoma.

Adenoma, Liver Cell↗
PubMed2001

Amplification of growth regulatory genes in intraductal breast cancer is associated with higher nuclear grade but not with the progression to invasiveness.

Ductal carcinoma in situ (DCIS), as an identifiable progenitor lesion of invasive breast cancer, represents a morphologically, biologically, and prognostically heterogeneous disease. It is not clear which molecular mechanisms are involved in progression to infiltrative growth. In this study, 83 DCIS classified according to the Van Nuys grading scheme were examined for amplification of growth regulatory genes that have been found to be amplified in invasive breast cancer (c-erbB2, topoisomerase IIalpha, c-myc, and cyclinD1 genes). Exact quantification of gene amplification was enabled by a combination of laser microdissection of paraffin-embedded tissue with real-time PCR. In DCIS, gene amplifications of all tested genes were found. The most frequently amplified gene was c-erbB2 found in 21 of 83 (25%) cases. Amplification of the other genes under investigation was observed in 4% to 6% of cases, high-grade DCIS being predominantly affected. High-grade DCIS differed significantly from low- and intermediate-grade DCIS in frequency and level of c-erbB2 amplification. In addition, high-grade DCIS revealed an accumulation of genetic aberrations. Amplification status in pure in situ lesions did not differ from intraductal carcinoma with an infiltrative component, indicating that although associated with a higher nuclear grade gene amplification might not represent an independent prognostic marker of disease progression.

Breast Neoplasms↗