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O Kaufmann

Publications and source records attributed to O Kaufmann.

35 records · Page 2Linked to original sources
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↗
PubMed2000

AgNOR analysis of atypical ductal hyperplasia and intraductal carcinoma of the breast.

OBJECTIVE: To determine the diagnostic and prognostic value of argyrophilic nucleolar organizer regions (AgNORs) in atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and microinvasive ductal carcinoma (MDCA) of the breast. STUDY DESIGN: Image analysis of histologic sections from biopsies of 46 breast ADH and DCIS and 18 cases of MDCA. Determination of morphometric features of cell nuclei and nucleolar organizer regions by using AMBA software system. Data were compared with the estrogen receptor/progesterone receptor (ER/PR) content as well as with the growth fraction, determined immunohistochemically. RESULTS: AgNOR number and total AgNOR area increased from ADH to DCIS. The highest values were recorded in cases of DCIS with microinvasion. Differences between ADH and intraductal or microinvasive ductal carcinoma were statistically significant. Within the group of intraductal carcinomas, the lowest values were measured in the solid type and highest values in the comedo type. A correlation was found between AgNOR features and growth fraction but not between these features and ER/PR status. CONCLUSION: Selected AgNOR features are relevant for differentiation between ADH and DCIS as well as between low and high grade DCIS and microinvasive ductal carcinoma. Therefore, objective and reproducible data obtained by AgNOR analysis may allow better evaluation of the prognostic significance of these lesions.

Biomarkers, Tumor↗
PubMed1999

Immunohistochemical detection of CD10 with monoclonal antibody 56C6 on paraffin sections.

We tested a total of 174 paraffin-embedded hematolymphoid neoplasias to determine whether CD10 can be specifically and sensitivity detected on paraffin sections using monoclonal antibody 56C6 after epitope retrieval. For 32 cases, results of CD10 detection by immunohistochemistry were compared with flow cytometric data. In only 1 case of follicle center lymphoma, divergent staining results were found with the detection of CD10 by flow cytometry but not by immunohistochemistry. Altogether, 22 of 28 follicle center lymphomas, 2 of 6 hairy cell leukemias, 14 of 34 diffuse large B-cell lymphomas, 3 of 3 Burkitt lymphomas, 4 of 5 precursor B-lineage acute lymphoblastic leukemias, and 2 of 4 T-lymphoblastic lymphomas were CD10+. Decalcification of bone marrow biopsy specimens did not diminish the staining intensity. All other cases, including 10 acute myeloid leukemias and a range of low-grade B-cell lymphomas, were CD10-. CD10 is reliably detectable with antibody 56C6 on paraffin sections using epitope retrieval. The antibody is especially useful for the subclassification of acute leukemias and low-grade B-cell lymphomas.

Antibodies, Monoclonal↗
PubMed1998

Detection of oestrogen receptors in non-invasive and invasive transitional cell carcinomas of the urinary bladder using both conventional immunohistochemistry and the tyramide staining amplification (TSA) technique.

In a retrospective immunohistochemical study, the expression of oestrogen receptors has been investigated in paraffin-embedded transitional cell carcinomas of the urinary bladder with antibody 6F11, using both a conventional immunohistochemical detection system and the highly sensitive tyramide staining amplification (TSA) technique. The study comprised 88 invasive and 97 non-invasive carcinomas of 101 female (mean age 68.4 years) and 84 male (mean age 68.2 years) patients. Oestrogen receptors were detected in 34 (18 per cent) carcinomas with conventional immunohistochemistry and 46 (25 per cent) with TSA. Using TSA, oestrogen receptors were significantly more often detectable in invasive (32/88) than in non-invasive carcinomas (14/97) and in G2/G3 (37/122) rather than in G1 (9/63) carcinomas. There were no associations between patients' age and sex and the expression of oestrogen receptors. The functional significance of oestrogen receptor expression in a subset of transitional cell carcinomas of the urinary bladder remains to be determined.

Adult↗
PubMed1998

Chromosome alterations in breast carcinomas: frequent involvement of DNA losses including chromosomes 4q and 21q.

Comparative genomic hybridization was applied to map DNA gains and losses in 39 invasive ductal breast carcinomas. Frequent abnormalities included gains on chromosomal regions 1q, 8q, 11q12-13, 16p, 19, 20q and X as well as frequent losses on 1p, 5q, 6q, 9p, 11q, 13q and 16q. Furthermore, frequent losses on 4q (20 cases) and 21q (14 cases) were found for the first time in this tumour type. High copy number amplifications were observed at 8q12-24, 11q11-13 and 20q13-ter. Highly differentiated tumours were associated with gains on 1q and 11q12-13 along with losses on 1p21-22, 4q, 13q, 11q21-ter. Undifferentiated breast carcinomas were characterized by additional DNA imbalances, i.e. deletions of 5q13-23, all of chromosome 9, the centromeric part of chromosome 13 including band 13q14 and the overrepresentation of chromosome X. We speculate that these changes are associated with tumour progression of invasive ductal breast cancer.

Breast Neoplasms↗
PubMed1998

Use of antibodies against estrogen and progesterone receptors to identify metastatic breast and ovarian carcinomas by conventional immunohistochemical and tyramide signal amplification methods.

The immunohistochemical detection of estrogen receptors (ERs) and progesterone receptors (PRs) is useful for the differentiation of cytostatically treatable breast and ovarian carcinomas from other metastatic adenocarcinomas of unknown primary sites. We retrospectively studied metastases of 68 breast, 24 ovarian, 15 bronchogenic, 35 gastric, 22 pancreatic, 23 colonic, 27 renal cell, and 26 primary bronchogenic carcinomas by using a panel of 3 antibodies against ERs and 4 antibodies against PRs and applying both a conventional immunohistochemical detection method and the highly sensitive tyramide signal amplification (TSA) technique. Antibody 6F11 against ERs was slightly more sensitive than clone 1D5 with both detection methods, staining 5% more breast carcinomas and 4% more ovarian carcinomas with TSA, compared with conventional immunohistochemical analysis. Furthermore, clone 6F11 detected ERs in 4 of 26 primary bronchogenic carcinomas and 1 of 35 metastases of gastric carcinomas with conventional immunohistochemical techniques; an additional 9 primary and 6 metastatic bronchogenic carcinomas and 2 metastatic gastric carcinomas were positive with TSA. The resulting specificities for breast and ovarian carcinomas versus all other carcinomas were 0.97 with conventional immunohistochemical techniques and 0.85 with TSA. Antibody 1A6 against PRs was slightly more sensitive but least specific for breast and ovarian carcinomas (specificity was 0.96 with conventional immunohistochemical methods and 0.91 with TSA), compared with antibody hPRa3 and a polyclonal antibody (specificity was 1.00 with both detection methods). Antibodies TE111 against ERs and 10A9 against PRs were significantly less sensitive than the other antibodies. We conclude that TSA cannot be recommended for the detection of ERs and PRs to differentiate breast and ovarian carcinomas from other metastatic adenocarcinomas of unknown primary sites.

Antibodies, Monoclonal↗
PubMed1998

Tyrosinase, melan-A, and KBA62 as markers for the immunohistochemical identification of metastatic amelanotic melanomas on paraffin sections.

The authors retrospectively tested the potential value of paraffin-reactive monoclonal antibodies (A103 against melan-A, T311 against tyrosinase) and antibody KBA62 as immunohistochemical markers for amelanotic metastatic melanomas. The study cases included 72 amelanotic metastases of known cutaneous melanomas, 59 poorly differentiated carcinomas, 73 sarcomas of varying histogenesis, 4 Leydig cell tumors, 10 high-grade lymphomas, and 6 plasmoblastic/anaplastic myelomas. The results were compared with immunostainings for S-100 protein and HMB-45. HMB-45, antimelan-A, and antityrosinase showed almost identical staining results, with a sensitivity of 0.85 for HMB-45 and of 0.86 for both antimelan-A and for antityrosinase. HMB-45 and antityrosinase both had a specificity of 1.00; the specificity of antimelan-A was 0.95 as a result of a positive reaction in three of three adrenocortical carcinomas and four of four Leydig cell tumors. KBA62 stainings resulted in a sensitivity of 0.86 for melanomas. A positive immunoreactivity of KBA62 alone had a specificity of only 0.83, but in conjunction with anti-S-100 protein (sensitivity, 1.00; specificity, 0.87) and anticytokeratin 8/18/19 (CK), a KBA62+/S-100+/CK- immunophenotype identified all except one of the melanoma cases that were negative for the three melanocyte-specific markers with a specificity of 0.99. In conclusion, we found comparable immunohistochemical sensitivities of HMB-45, antityrosinase, and antimelan-A for a highly specific identification of approximately 85% of amelanotic metastatic melanomas on paraffin sections. Melanomas that were negative for all of these specific markers might be sensitively and specifically detected with anti-S-100 protein and KBA62.

Antibodies, Monoclonal↗
PubMed1997

Utility of 123C3 monoclonal antibody against CD56 (NCAM) for the diagnosis of small cell carcinomas on paraffin sections.

CD56 is immunohistochemically detectable in virtually all small cell carcinomas on frozen sections. The authors retrospectively tested the usefulness of the monoclonal antibody 123C3 against CD56 to differentiate pulmonary and extrapulmonary small cell carcinomas from nonneuroendocrine non-small cell carcinomas by paraffin-section immunohistochemistry after antigen retrieval. The study included 70 small cell carcinomas and 344 primary and metastatic nonneuroendocrine carcinomas of various primary sites. The staining results were compared with specific neuroendocrine markers (CD57, Chromogranin A, Synaptophysin). The monoclonal antibody 123C3 diffusely stained most small cell carcinomas with a strong membranous pattern (sensitivity: 0.99). The staining intensity was not diminished in areas with crush artifacts or after decalcification. The neuroendocrine markers had a combined sensitivity of only 0.44 for small cell carcinomas. With regard to nonneuroendocrine carcinomas, the 123C3 antibody stained 7 of 28 ovarian carcinomas, 6 of 30 renal cell carcinomas, 2 of 10 endometrial carcinomas, two of three nonneuroendocrine large cell carcinomas of the lung, 1 of 38 adenocarcinomas, and 4 of 52 squamous cell carcinomas of the lung. Urothelial carcinomas, hepatocellular carcinomas, squamous carcinomas of the head/neck and cervix uteri, as well as adenocarcinomas of the breast, stomach, colon, pancreas, and prostate, showed no immunoreactivity for CD56. The specificities of 123C3 and the combined neuroendocrine markers for small cell carcinomas were 0.94 and 0.95, respectively. The authors conclude that monoclonal antibody 123C3 might be useful for the immunohistochemical differentiation of small cell carcinomas from nonneuroendocrine carcinomas on paraffin sections, especially in small and crushed biopsy specimens.

Antibodies, Monoclonal↗
PubMed1997

Immunohistochemical differentiation of metastases of renal carcinomas versus other carcinomas with anti-gamma GT monoclonal antibody 138H11.

AIMS: Adenocarcinomas account for about 60% of metastatic cancers of unknown primary (CUP) site. In such a clinical CUP situation, histopathologists are challenged to differentiate renal cell carcinomas (RCC) from other adenocarcinomas with similar immunophenotypes, especially chemotherapeutically treatable mammary and ovarian carcinomas. METHODS AND RESULTS: Recently, we produced a monoclonal antibody (mAb), designated 138H11, against human gamma-glutamyl-transferase (gamma GT), which stained over 98% primary clear cell and chromophilic RCC on frozen sections. The 138H11 epitope could not be stained using conventional techniques in most paraffin-embedded sections of the same origin, due to destruction by formalin fixation below the detection level. Here, we demonstrate that mAb 138H11 can specifically stain gamma GT in paraffin-embedded primary and metastatic RCC after enhancement with an ultrasensitive immunohistochemical method. We analysed a selected subgroup of adenocarcinomas with immunophenotypes which would not allow a differentiation from RCC in a CUP situation. We found a predominantly membranous expression of the 138H11 target antigen in 26/51 primary RCC and 15/ 34 metastatic RCC. In contrast, all 43/43 primary ovarian and bronchial carcinomas as well as 54/54 metastases of ovarian, mammary, bronchial and gastric carcinomas were negative for mAb 138H11. CONCLUSIONS: The data suggest that mAb 138H11 is useful for the immunohistochemical differentiation of RCC from other metastatic adenocarcinomas if the primary site of the tumour is not known.

Antibodies, Monoclonal↗
PubMed1997

Immunohistochemical detection of CD5 with monoclonal antibody 4C7 on paraffin sections.

CD5 is useful for the classification of low-grade B-cell lymphomas, because it is aberrantly expressed in B-cell chronic lymphocytic leukemias/small lymphocytic lymphomas (B-CLLs/SLLs) and mantle cell lymphomas (MCLs), but not in the other well-described low-grade B-cell lymphomas. Therefore, we tested the utility of monoclonal antibody (MAb) 4C7 to detect CD5 on paraffin sections of 22 cases with low-grade B-cell lymphomas and 4 cases with high-grade B-cell lymphomas and compared the results with CD5 detection by analysis of fresh tissue with a fluorescent-activated cell sorting (FACS). After heat-induced epitope retrieval we could detect CD5 on paraffin sections in all MCLs and B-CLLs/SLLs, identical to the results of flow cytometry. Eleven of 12 cases that showed no CD5 expression by FACS analysis were also negative on paraffin sections. In only one case of a presumed blastoid MCL, CD5 was detectable by immunohistochemistry but not by FACS analysis. We conclude that MAb 4C7 against CD5 is a useful paraffin-reactive marker, especially to correctly identify MCLs on paraffin sections.

Antibodies, Monoclonal↗
PubMed1996

Subcutaneous crystal-storing histiocytosis associated with lymphoplasmacytic lymphoma (immunocytoma)

A case of massive crystal-storing histiocytosis with extensive involvement of the subcutaneous adipose tissue in a 61-year-old caucasian woman with a lymphoplasmacytic lymphoma (immunocytoma) in transformation to a large cell lymphoma is presented. Paraffin-section immunohistochemistry demonstrated a monoclonal IgM/ kappa immunphenotype of the lymphoma cells and revealed IgM/kappa and, to a lesser extent, IgG/lambda in the crystal-containing histiocytes. Ultrastructurally, the electron dense intracytoplasmic crystals had variables shapes, were occasionally membrane-bound and measured up to 6 microns. The finding are briefly discussed.

Crystallization↗
PubMed1996

Immunohistochemical differentiation of metastatic breast carcinomas from metastatic adenocarcinomas of other common primary sites.

To test the possibility of immunohistochemical differentiation of cytostatically treatable metastatic breast carcinomas from other metastatic adenocarcinomas of unknown primary site, we studied a total of 328 metastatic adenocarcinomas including 35 bronchogenic, 26 pancreatic, 25 colonic, 39 gastric, 45 renal, 29 ovarian and 129 breast carcinomas with a panel of 13 commercially available monoclonal antibodies. The expression of gross cystic disease fluid protein 15 and/or oestrogen or progesterone receptors had a sensitivity of 0.83, a specificity of 0.93 and a predictive accuracy of 0.92 for carcinomas of the breast against all other carcinomas. Excluding ovarian carcinomas, this combination had a sensitivity, specificity and predictive accuracy for mammary carcinomas of 0.83, 0.98 and 0.98, respectively. Carcinoembryonic antigen and/or cytokeratin 20 identified bronchogenic, gastric, pancreatic and colorectal carcinomas versus breast carcinomas lacking gross cystic disease fluid protein 15 and oestrogen or progesterone receptors with a sensitivity, specificity and predictive accuracy of 0.82, 0.99 and 0.95, respectively. Vimentin differentiates renal cell carcinomas from gross cystic disease fluid protein 15 and oestrogene or progesterone receptor negative breast carcinomas with a sensitivity, specificity and predictive accuracy of 0.93, 0.82 and 0.84. Thus, it should be possible to differentiate most metastatic mammary carcinomas from metastatic adenocarcinomas of other common primary sites, even if the former lack expression of gross cystic disease fluid protein 15 and oestrogen or progesterone receptors.

Adenocarcinoma↗
PubMed1990

[Subjective wellbeing of shift workers in relation to individual characteristics of circadian rhythm].

With a goal to test the influence of individual traits of circadian rhythms on the tolerance of shiftwork a circadian questionnaire has been developed with the method of factors analysis. There are two scales in the final form of the questionnaire representing two chronobiological characteristics: morningness - eveningsness (circadian phase-position) and flexibility of the sleep-wake-rhythm. Sex- and age-norms exist for the two scales. Reliability and validity have been demonstrated. The results of an epidemiological study shows that the hypothesis of better adjustment to shiftwork of evening-types can not be verified. A better predictor of tolerance to shift work in terms of wellbeing seems to be the individual circadian trait flexibility of sleep-wake-rhythm.

Adaptation, Physiological↗