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O Kaufmann

Publications and source records attributed to O Kaufmann.

At least 19 recordsLinked to original sources
PubMed2003

[Solitary renal cell carcinoma metastasis to the thyroid gland--a paradigm of metastasectomy?].

We investigated the usefulness of thyroidectomy for solitary metastases from renal cell carcinomas in ten patients. In the absence of postoperative morbidity and mortality, a mean survival time of 3.4 years was observed. Subsequently, four patients developed intracerebral metastases. Swelling of the neck and the discovery of a nodule in the thyroid of patients who have undergone nephrectomy for renal cell carcinoma should raise suspicion of a metastasis, possibly after a long latency period. With the aid of modern immunohistochemical methods, renal cell carcinoma metastasis can now be identified unequivocally, with differentiation from a primary follicular carcinoma of the thyroid rendered possible by a combination of TTF-1, thyroglobulin, and CD 10. In the event of a solitary lesion with no extrathyroidal tumour manifestation, an R0 resection of the metastasis should always be attempted. If tumour dissemination has occurred, palliative measures and endoscopic intervention (e.g. placement of an endotracheal stent) with the aim of improving quality of life by preventing obstruction of the airways are justified.

Adenocarcinoma, Follicular↗
PubMed2003

Comparison of immunoglobulin heavy chain rearrangements between peripheral and glandular B cells in a patient with primary Sjögren's syndrome.

Myoepithelial sialadenitis (MESA) of the major salivary glands is a characteristic feature of primary Sjögren's syndrome (pSS). To delineate systemic and organ-specific influences on B cells in a patient with pSS and benign MESA, individual B cells were simultaneously obtained from the peripheral blood and inflamed parotid gland. Immunoglobulin variable heavy chain (VH) rearrangements in single sorted CD19+ B cells were subsequently amplified, sequenced and analysed. Despite the presence of two clonal expansions using VH1-08 and VH2-70 segments, respectively, the majority of glandular B cells were polyclonal, resembling the VH gene usage and mutational pattern of the corresponding blood population. However, striking differences were observed in the proportion of cells expressing mutated VH rearrangements (blood, 28.9% versus parotid, 80.4%; P < 0.0001). Moreover, the glandular productive VH rearrangements differed significantly from their blood counterparts by a higher mutational frequency (P < 0.0001), shorter CDR3 lengths (P = 0.001) and a less frequent usage of JH6 (P = 0.0292), indicating an accumulation of memory B cells in the inflamed parotid. Thus, both preferential influx/homing of memory B cells and local proliferation may contribute to the pattern of benign MESA in pSS. Notably, one of the glandular clonal rearrangements (using VH1-08) was also detected in the patient's peripheral repertoire.

Aged↗
PubMed2002

[Immunohistochemical diagnosis in cancer metastasis of unknown primary tumor].

Immunohistochemical studies on metastatic carcinomas of unknown primary site are cost-effective and often allow a specific identification of the tumour origin, especially if the metastases are adenocarcinomas by light microscopy. Commercially available site-specific markers include prostate-specific antigen, thyroglobulin, thyroid transcription factor-1, uroplakin III, GCDFP-15, oestrogen and progesterone receptors, alpha-fetoprotein, the A103 monoclonal antibody against MART-1, cytokeratins 7 and 20, cytokeratins of basal cell type, p63, carcinoembryonic antigen, CA125, EMA, vimentin, HepPar-1, WT-1 and S100 protein. However, immunostaining with most of these markers does not show an absolute specificity for a certain primary site. For this reason, histopathologists interpretating staining results with these markers should take the available clinical data and the histological features of the metastatic carcinoma into consideration. These data are necessary to estimate the relative a priori probability of possible carcinomas. Based on Bayes' theorem, the a priori probability can then be used to calculate the diagnostically relevant predictive values for immunostaining results with the chosen markers.

Biomarkers, Tumor↗
PubMed2001

Relationship between bone marrow angiogenesis and plasma cell infiltration and serum beta2-microglobulin levels in patients with multiple myeloma.

There is growing evidence that angiogenesis is important not only in solid tumors but also in hematological malignancies. Recently, we found that bone marrow angiogenesis is a prognostic factor for disease-related survival in patients with multiple myeloma. In this report, we addressed the question of whether the microvessel density in bone marrow biopsies is correlated to other myeloma parameters, e.g., serum beta2-microglobulin (beta2-MG) and plasma cell infiltration in the bone marrow. In 22 multiple myeloma patients, immunohistochemical, CD34-stained, paraffin-embedded bone marrow biopsies before and after chemotherapy were studied. Microvessels were counted in 400x magnification, and the mean number of vessels per area in each sample was noted as the microvessel density (MVD). Pretreatment bone marrow MVD (median: 44, range: 11-175 vessels/mm2) correlated significantly with the bone marrow plasma cell infiltration (median: 30%, range: 5-90%, r = 0.642, P=0.001) and beta2-MG (median: 2.74, range: 1.4-26.1 mg/l, r = 0.749, P < 0.0005). In contrast, there was no correlation between posttreatment MVD and plasma cell infiltration or beta2-MG (median: MVD 31, range: 0-221 vessels/mm2, median plasma cell infiltration: 15%, range: 5-80%, r = 0.229, P = 0.306 and median beta2-MG: 2.65, range: 1-27.6 mg/l, r = -0.042, P = 0.853). These findings show that the strong correlations between bone marrow MVD and plasma cell infiltration as well as serum beta2-MG levels disappear after chemotherapy. The underlying mechanisms need further investigations.

Biopsy↗
PubMed2001

Overexpression of c-erbB2 protein correlates with disease-stage and chromosomal gain at the c-erbB2 locus in non-small cell lung cancer.

Overexpression of the c-erbB2 protein is observed in a variety of malignancies including non-small cell lung cancer (NSCLC). We aimed to determine the rate of c-erbB2-overexpression in our tumour collection and to clarify its correlation with the chromosomal status at the c-erbB2 locus 17q21 in NSCLC. Eighty-nine NSCLC were analysed immunohistochemically using a polyclonal c-erbB2 antibody (DAKO). The staining was scored according to the guidelines of the Clinical Trial Assay recommendations (0-3+). Of these, 44 cases were also analysed by comparative genomic hybridisation (CGH). Overexpression was observed in 37% of the cases (score>1) which was associated with higher disease stages and a positive nodal status in adenocarcinomas. Chromosomal gains at 17q21 were clearly correlated with overexpression of the gene (P=0.009). In addition, there was a highly significant correlation between the c-erbB2 expression comparing the whole section immunostaining analysis and a 127 lung tumour tissue array which included 74 of the 89 cases that were analysed by the classical procedure. We conclude that c-erbB2 is a marker of tumour progression in NSCLC which can be observed on protein level and reflects chromosomal alterations at 17q21.

Adult↗
PubMed2001

Achievement of complete remission in refractory Hodgkin's disease with prolonged infusion of gemcitabine.

Although, in recent decades effective chemotherapy regimens have been developed for the treatment of Hodgkin's disease, the prognosis of patients who experience disease progression is still very poor. New treatment approaches are urgently required to salvage such patients. In a patient with Hodgkin's disease who failed to achieve complete remission with the escalated BEACOPP protocol, progression with bone marrow infiltration and B symptoms developed despite further treatment. Subsequently, gemcitabine was administered in a novel schedule as a four-hour infusion of 250 mg/m2 on days 1, 8, and 15, every four weeks. After the first cycle, the dose was reduced to 200 mg/m2 because of grade 3 neutropenia. The condition of the patient improved after the second cycle and no toxicity was observed during cycles 3-6. Complete remission was achieved. Two years after the end of gemcitabine therapy, the patient is in good clinical condition and in continuous complete remission without further treatment. This is the first report of the prolonged infusion of gemcitabine as a salvage therapy in Hodgkin's disease.

Adult↗
PubMed2001

Decrease of bone marrow angiogenesis in myeloma patients achieving a remission after chemotherapy.

The impact of angiogenesis is well known for the growth and viability of solid tumors. Fewer studies have been published relating angiogenesis to clinical or pathological parameters in hematological malignancies. In this report, we have estimated the bone marrow microvessel density (MVD) before and after conventional-dose or high-dose chemotherapy with autologous stem cell transplantation. Immunohistochemical CD34-stained paraffin-embedded bone marrow biopsies of 21 patients with stage III multiple myeloma were studied. Microvessels were counted at 400x magnification, and the mean number of vessels per area in each sample was noted as the MVD. The median MVD of all patients was 53.1 vessels/mm2 (range 15.5-174.7 vessels/mm2) before treatment and 29.3 vessels/mm2 (range 0-221.1 vessels/mm2) after chemotherapy. The post-treatment MVD in the two groups of patients with and without remission was significantly different (p=0.001), whereas the pretreatment MVD was not. Responders but not nonresponders showed a significant decrease of MVD after therapy in comparison to their pretreatment levels. The progression-free survival in patients who achieved a reduction in MVD after chemotherapy was significantly longer than in patients without a decrease in MVD (P=0.006). Furthermore, we compared the MVD of patients after achievement of a remission to MVD of 15 untreated stage I myeloma patients. The MVD of patients in remission was not statistically different from the MVD in stage I myeloma. These results underscore the impact of angiogenesis in myeloma and give the first report that effective chemotherapy is accompanied by a significant decrease in bone marrow angiogenesis in this disease.

Aged↗
PubMed2001

Microsatellite instability is infrequent in medullary breast cancer.

Microsatellite instability (MSI), characterized by contraction or expansion in microsatellite length or short tandem repeats compared with germline lengths, is found in 85% to 90% of colon cancer arising in hereditary nonpolyposis colorectal cancer families. These cancers commonly have characteristic histologic appearances, including medullary features with intense lymphoid infiltrates. In pancreatic cancer, a rare medullary histologic subtype more often demonstrates MSI than the more common adenocarcinoma subtype. We hypothesized that the medullary histologic pattern might correlate with MSI in additional tumor types and analyzed 8 cases of typical and atypical medullary carcinoma of the breast. Tumor and normal DNA was extracted from paraffinized tissue blocks of tumor and histologically uninvolved axillary lymph nodes, respectively. We analyzed the tumors for instability in 5 primary (BAT25, BAT26, D17S250, D5S346, D2S123) and 3 alternative (BAT40, D18S55, D18S58) microsatellites recommended at the National Cancer Institute--sponsored conference for diagnosis of MSI in colorectal cancer. All 8 tumors were microsatellite stable at the 8 loci, suggesting that MSI is not commonly associated with medullary or atypical medullary breast carcinoma, in contrast with the reported association with medullary tumors of the colon and pancreas.

Adult↗
PubMed2000

Vascular endothelial growth factor and its correlation with angiogenesis and p53 expression in prostate cancer.

BACKGROUND: Previously it was demonstrated that in prostate tumors, angiogenesis measured as microvessel density (MVD) is associated with tumor stage as well as WHO grade and is an independent predictor of clinical outcome. Vascular endothelial growth factor (VEGF) is a major inducer of angiogenesis. There is some evidence that P53 mutations cause overexpression of VEGF. We studied VEGF expression, p53 overexpression, and P53 mutations in prostate cancer (PCA) to investigate the role of VEGF as an angiogenic marker and the possible deregulation of VEGF as a result of P53 mutations in PCA. METHODS: Immunohistochemical staining with a polyclonal VEGF antibody was performed in 55 paraffin-embedded PCA, in which MVD had previously been determined, as well as in 5 prostatic adenomas (PA) and 20 adjacent normal prostate tissues. In addition, 37 PCA and 5 PAs were examined for p53 expression by immunohistochemistry. Temperature gradient gel electrophoresis (TGGE) was performed in 13 of these PCA to screen for P53 mutations. VEGF expression, p53 expression, and mutations were then correlated with tumor stage, grade, MVD, and clinical outcome. RESULTS: While PA and normal prostate tissue generally showed no or only low VEGF expression, there was a significant increase in VEGF expression with tumor stage, grade, and MVD in PCA. During clinical follow-up (mean, 31.9 months), 9 of 55 patients had tumor progression. Significant differences in VEGF expression were found between patients with tumor progression and those without (P = 0.0004). Of the 37 PCA evaluated for p53 expression, 12 exhibited p53 overexpression. TGGE revealed P53 mutations in 3 of 13 PCA. However, there was no correlation between VEGF expression, p53 overexpression, and P53 mutation, respectively. CONCLUSIONS: VEGF seems to be an important, clinically relevant inducer of angiogenesis in PCA. VEGF expression was shown to correlate positively with tumor stage, grade, MVD, and clinical outcome. However, regulation of VEGF in PCA appears to be independent of p53 expression.

Adult↗
PubMed2000

Specificity of PCR-based clonality analysis of immunoglobulin heavy chain gene rearrangements for the detection of bone marrow involvement by low-grade B-cell lymphomas.

A study was performed to investigate the utility of polymerase chain reaction (PCR)-based analysis of immunoglobulin heavy chain (IgH) gene rearrangements for the diagnosis of low-grade malignant B-cell lymphomas on formalin-fixed, EDTA-decalcified, and paraffin-embedded bone marrow trephine biopsies. On amplifying two DNA samples per biopsy, no reproducible monoclonal PCR result was found in 32 patients with reactive lymphoid hyperplasias. In contrast, 5/14 patients with known low-grade B-cell lymphomas, but histomorphologically and immunohistochemically lymphoma-free bone marrow, showed a reproducible monoclonal IgH gene rearrangement. In three of these cases, sequence analysis revealed completely different amplification products on comparing bone marrow and lymph node infiltrations, while in the other two cases the products were identical. In one of the latter biopsies, an unequivocal lymphoma infiltrate was found after step sectioning of the biopsy, while the other case remained lymphoma-free according to conventional criteria. A third group of three patients with known lymphomas and bone marrow findings that were suggestive but not diagnostic of bone marrow involvement showed monoclonal PCR results in all three cases, with identical sequences in bone marrow and extramedullary lymphoma infiltrates. These data suggest that a reproducible monoclonal IgH gene rearrangement is highly specific for the presence of malignant B-cells in bone marrow. In staging procedures for low-grade B-cell lymphomas, PCR yields no additional information in cases that are morphologically and immunohistochemically lymphoma-free after evaluation of representative sections. PCR may be useful in equivocal cases, provided that IgH gene rearrangements of extramedullary lymphoma and bone marrow are sequenced and compared.

Adult↗
PubMed2000

Tumor angiogenesis is associated with progression after radical prostatectomy in pT2/pT3 prostate cancer.

BACKGROUND: The clinical relevance of tumor angiogenesis has been investigated in several human tumor types. Angiogenesis (measured as microvessel density; MVD) was recently correlated with tumor stage, grade, and clinical course in prostate cancer (PC). However, considerable controversy remains concerning the prognostic value of angiogenesis in PC. METHODS: We examined MVD in primary PCs to further establish the prognostic relevance of angiogenesis in this tumor entity. In 98 paraffin-embedded PCs of various stages, 5 prostate adenomas, and 20 normal prostate tissues, MVD was determined immunohistochemically using a polyclonal antibody against factor VIII. The findings were correlated with the clinical data of the patients. RESULTS: Normal prostate tissue and prostate adenomas had a low MVD. In PC, MVD increased significantly with tumor stage and grade (P < 0.001). The Wilcoxon rank statistics showed significant differences for MVD (P < 0.0001), tumor stage (P < 0. 0027), and grade (P < 0.0001), but not for preoperative prostate-specific antigen values in PC patients with and without tumor progression subsequent to treatment, respectively. Importantly, multivariate survival analysis revealed that MVD and tumor grade were the only independent markers for progression in prostate carcinoma. CONCLUSIONS: In this study, tumor angiogenesis measured by MVD was associated with a dismal pathologic appearance and a negative clinical prognosis in PC after radical prostatectomy.

Blood Vessels↗
PubMed2000

Bone marrow microvessel density is a prognostic factor for survival in patients with multiple myeloma.

The importance of neoangiogenesis for the progressive growth and viability of solid tumors is well established. Recently, there has been growing evidence that angiogenesis might also be important in hematological malignancies, but only few data are available. In this report, we have studied the impact of bone marrow microvessel density and survival in patients with multiple myeloma (MM). Immunohistochemical CD34 stained paraffin-embedded bone marrow biopsies of 44 patients with newly diagnosed MM were studied. Microvessels were counted in 400 x magnification and the mean number of vessels per area in each sample was noted as the microvessel density (MVD). The median MVD was 48 vessels/mm2, the range was 0-125 vessels/mm2. Using a cut-off value of the median MVD in the Kaplan-Meier analysis, the median survival was 22.2 months in the group with the higher MVD and was not reached in the group with the lower MVD (P< 0.01). In a multivariate Cox regression analysis, using previously identified prognostic factors beta2-microglobulin, C-reactive protein (CRP), and age, MVD remained significant as a prognostic factor (P< 0.03).

Adult↗
PubMed2000

An unusual case of leukemic non-Hodgkin's lymphoma with blastic transformation.

We report on a patient who was diagnosed as having B-cell chronic lymphocytic leukemia (CLL) with atypical morphology. Flow cytometry disclosed CD5, CD19, and CD23 positivity, an immunophenotype seen mostly in B-CLL. Histology of the spleen and bone marrow suggested a diagnosis of small lymphocytic lymphoma. Upon blastic transformation, only 3 years after the diagnosis had been made, unusual clinical and laboratory features emerged. Lymphoid blasts appeared in the peripheral blood, and the patient developed nodular infiltrates consisting of these blasts at recent venous puncture sites. The patient did not respond to chemotherapy and died. The lymphoid blasts in the peripheral blood were CD5-, CD19+, and CD23+ and harbored t(11;14) (q13;q32) and t(11;21)(p11;q21) translocations. To account for the possibility of two independent lymphoid malignancies, molecular genetic analyses were performed on samples from the spleen, bone marrow and a lymph node with the large-cell lymphoma, which showed identical clones in these tissues. This unusual case supports the idea that in leukemic non-Hodgkin's lymphoma, in addition to morphology, an accurate diagnostic workup requires immunophenotypic, cytogenetic, and molecular studies.

CD5 Antigens↗
PubMed2000

Thyroid transcription factor-1 is the superior immunohistochemical marker for pulmonary adenocarcinomas and large cell carcinomas compared to surfactant proteins A and B.

AIMS: Antibodies against the thyroid transcription factor-1 (TTF-1) and the surfactant proteins A and B (SPA, SPB) were compared as paraffin-reactive immunohistochemical markers for non-small cell carcinomas of pulmonary origin. METHODS AND RESULTS: We studied 138 carcinomas of pulmonary origin (98 adenocarcinomas, 20 non-neuroendocrine large cell carcinomas, 20 squamous cell carcinomas) and a total of 276 extrapulmonary carcinomas of various primary origins. Using the monoclonal antibody 8G7G3/1, TTF-1 was detectable in 75% of non-mucinous pulmonary adenocarcinomas and in 40% of large cell carcinomas but in only 10% of mucinous adenocarcinomas and not in squamous cell carcinomas. In contrast, both SPA and SPB were positive in only 45% of pulmonary adenocarcinomas and in 10% and in 5% of the large cell carcinomas, respectively. TTF-1 had a specificity of 0.98 for pulmonary carcinomas as 5/7 thyroid carcinomas were the only TTF-1-positive extrapulmonary tumours. Anti-SPB and anti-SPA had specificities of 1. 00 and 0.97, respectively. CONCLUSIONS: The monoclonal antibody 8G7G3/1 against TTF-1 should be the first choice as a component of an antibody panel aiming to prove or to exclude the pulmonary origin of non-mucinous adenocarcinomas and non-neuroendocrine poorly differentiated carcinomas, especially in patients presenting with metastatic carcinomas of unknown primary site.

Adenocarcinoma↗
PubMed2000

Expression of thyroid transcription factor-1 in pulmonary and extrapulmonary small cell carcinomas and other neuroendocrine carcinomas of various primary sites.

AIMS: The thyroid transcription factor-1 (TTF-1) is a highly specific immunohistochemical marker for the identification of pulmonary adenocarcinomas and non-neuroendocrine large cell carcinomas, especially in patients presenting with metastatic carcinomas of unknown primary site. In this study we tested if anti-TTF-1 can also be used to verify a pulmonary origin of neuroendocrine carcinomas, placing emphasis on the discrimination of pulmonary small cell carcinomas (SCCs) from extrapulmonary SCCs and the distinction of SCCs from Merkel cell carcinomas of the skin. METHODS AND RESULTS: We studied 37 pulmonary SCCs, 15 SCCs of extrapulmonary origin, 4 pulmonary large cell neuroendocrine carcinomas (LCNECs), four extrapulmonary LCNECs, six medullary thyroid carcinomas, 16 Merkel cell carcinomas, and a total of 32 carcinoids/low-grade neuroendocrine carcinomas of pulmonary (12 cases) and extrapulmonary (20 cases) origin. Using the commercially available monoclonal antibody 8G7G3/1, TTF-1 was immunohistochemically detectable in 81% of pulmonary SCCs but also in 80% of extrapulmonary SCCs. Furthermore, anti-TTF-1 showed a positive staining in 50% of all pulmonary carcinoids, in one gastric carcinoid, in 2/4 of pulmonary, and 1/4 of extrapulmonary LCNECs. All medullary thyroid carcinomas were also TTF-1-positive. Merkel cell carcinomas were consistently TTF-1-negative. CONCLUSIONS: Our results suggest that in contrast to non-neuroendocrine carcinomas, anti-TTF-1 cannot be used to prove or to exclude a pulmonary origin of SCCs or LCNECs of unknown or uncertain primary site. Therefore, before using anti-TTF-1 as a marker for pulmonary carcinomas one should be sure to have excluded SCC and LCNEC. On the other hand, anti-TTF-1 might be used to specifically discriminate SCCs of various origin from Merkel cell carcinomas.

Antibodies, Monoclonal↗
PubMed2000

Chromosomal imbalances in brain metastases of solid tumors.

Metastases account for approximately 50% of the malignant tumors in the brain. In order to identify structural alterations that are associated with tumor dissemination into the central nervous system we used Comparative Genomic Hybridization (CGH) to investigate 42 brain metastases and 3 primary tumors of 40 patients. The metastases originated from lung cancer (14 cases), melanomas (7), carcinomas of breast (5), colon (5), kidney (5), adrenal gland (1) and thyroid (1). In addition, tumors of initially unknown primaries were assessed in 3 cases. The highest incidence of DNA gains were observed for the chromosomal regions 1q23, 8q24, 17q24-q25, 20q13 (>80% of cases) followed by the gain on 7p12 (77%). DNA losses were slightly less frequent with 4q22, 4q26, 5q21, 9p21 being affected in at least 70% of the cases followed by deletions at 17p12, 4q32q34, 10q21, 10q23-q24 and 18q21-q22 in 67.5% of cases. Two unusual narrow regional peaks were observed for the gain on 17q24-q25 and loss on 17p12. The incidence at individual loci can be viewed at our CGH online tumor database at http:// amba.charite.de/cgh/. The metastases of each tumor type showed a recurrent pattern of changes. In those cases with primary tumor and metastases available, the CGH pattern exhibited a high degree of conformity. In conclusion, our data suggests that specific genetic lesions are associated with tumor dissemination into the nervous system and that CGH analysis may be a useful supplementary tool for classification of metastases with unknown origin.

Brain Neoplasms↗
PubMed2000

Uroplakin III is a highly specific and moderately sensitive immunohistochemical marker for primary and metastatic urothelial carcinomas.

Uroplakins are specific differentiation products of terminally differentiated superficial urothelial cells. We tested the value of a new commercially available monoclonal antibody against uroplakin III (clone AU 1) as a paraffin-reactive immunohistochemical marker for primary and metastatic urothelial carcinomas. The study cases included 67 urothelial carcinomas of the urinary tract (35 primary tumors, 32 metastases) and 318 nonurothelial carcinomas, as well as 5 benign Brenner tumors and 2 transitional cell carcinomas of the ovaries. Uroplakin III was detected in 21 (60%) of the primary urothelial carcinomas and 17 (53%) of the metastases, resulting in an overall sensitivity of 0.57. The studied Brenner tumors also were immunoreactive for uroplakin III. All other studied carcinomas were consistently uroplakin III-negative (specificity 1.00). We found the new monoclonal antibody AU 1 against uroplakin III to be a highly specific paraffin-reactive immunohistochemical marker for urothelial tumors with a moderate sensitivity for the identification of primary and metastatic urothelial carcinomas.

Aged↗