- Email: [email protected]
Prognostic value of the chemokine receptor CXCR4 in breast cancer
Symposium: Breast Pathology / Pathology - Research and Practice 200 (2004) 304-306
305
Results: ELISA and Western blot analysis revealed significantly re-
Methods: We investigated 2197 breast tumors in a tissue microar-
duced levels of the uPA protein in stable transfected and siRNAtransfected cells, as compared to non-transfected control samples. Real-time PCR analysis exhibited similar results at the mRNA levels. Incubation of uPA-silenced cells with recombinant HMW-uPA and ATF revealed an increase of proliferation activity. Addition of LMW-uPA did not alter proliferation activity in a significant manner. Conclusions: According to our results, uPA induces cell proliferation in breast cancer by binding to its specific receptor uPAR. Stimulation of proliferation is mediated via the growth factor-like domain of ATF. The catalytic domain of uPA is not involved in this process.
ray (TMA). All tumor samples were formalin fixed and paraffin embedded. For determination of Her-2 status we used commercial test kits for IHC (HercepTest TM, DAKO) and for FISH (reagent kit, Vyois). Results: The HER-2 IHC results differed greatly between 1551 tumors with interpretable HER-2 FISH signals and 405 breast cancers showing no FISH signals. FISH informative tumors had higher IHC scores than FISH non-informative tumors. FISH and IHC results were strongly associated (p < 0.0001) and all expected clinico-pathological associations could be found in our tumor set. Conclusion: Overall, the data show that not only FISH but also IHC results are dependent on good tissue quality for successful analysis. Poor tissue quality can be easily identified in FISH analyses because of a lack of hybridization signals. Inappropriate tissue handling is more dangerous in IHC because an artificial lack of staining can be regarded as "negative" result.
191 A novel diagnostic approach for the simultaneous study of HER2/neu overexpression and gene amplification in human breast cancers C. LOTTNER, S. SCHWARZ, R. JUNG, R. KNUCHEL 1, F. HOFSTADTER, G. BROCKHOFF
193
Institut ftir Pathologie, Universit~it Regensburg 11nstitut ftir Pathologie, Unlversit~itsklinikum der RWTH Aachen
R. SIMON, S. PANUSSIS, K. GLATZ, C. TAPIA, M. MIRLACHER, M. MIHATSCH, G. SAUTER
Aims: HER2/neu is overexpressed in 25% to 30% of human breast
Institut ftir Pathologie, Universit~it Basel, Schweiz
cancers. In order to increase the accuracy mid to improve the reproducibility of the HER2/neu diagnostics - immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) - we established a novel diagnostic approach based on the simultaneous detection of HER2/neu gene amplification via FISH and the correlated protein expression via fluorescent IHC on paraffin-embedded tissue. Methods: The HER2/neu oncogene, located at 17q21, was detected using the PathVysion HER2 DNA Probe Kit (VYSIS). The HER2/neu gene region was visualized with yellow fluorescence; the centromere 17 probe was green fluorescent. The HER2/neu protein expression (red fluorescence) was detected simultaneously using an epifluorescence microscope. Paraffin-embedded breast cancer cell lines were used as a reference for both gene amplification and protein expression. The diagnostic applicability was verified on primary breast cancer tissue sections. Results: The simultaneous detection of the HER2/neu receptor protein and gene copy number is reliably feasible in the multiparametric fluorescent approach. The immunohistochemical determination of the HER2/neu receptor status is in concordance with the FDA approved scoring, ranging from 0 to 3+ conventionally applied in the HercepTest (DAKO). With the novel approach gene copy number and protein content can be analyzed in the same cell. Conclusion: The combined fluorescent detection of protein expression and gene copy number on paraffin-embedded material improves the diagnostic value of HER2/neu and will be the basis for the development of an automated HER2/neu detection system.
192 HER-2 analysis in breast cancer: Reduced immunoreactivity in FISH non-informative cancer biopsies C. TAPIA, P. SCHRAML, R. SIMON, M. MIRLACHER, H. NOVOTNY, M.J. MIHATSCH, G. SAUTER Institut for Pathology, University of Basel, Basel
Aims: Due to the central role in predicting response to Herceptin TM and possibly also other anti cancer drugs, accurate and reproducible detection of the Her-2 status is important. Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) are the most commonly used methods for HER-2 analysis. In some cases FISH results are not interpretable for some reasons. To investigate a possible influence of tissue damage on the results of HER-2 IHC we compared the HER-2 IHC results obtained in tumors with and without interpretable FISH in breast cancer tissues.
Evaluation of tissue microarray based HER2 diagnosis
Aims: Numerous studies have demonstrated that tissue microarrays (TMAs) are adequately representative for their donor tissues in a research setting. But considering the increasing demand for predictive molecular tumor analysis, TMAs may also become relevant for diagnostic applications. Here, we evaluated the applicability of TMAs for HER2 diagnosis. Methods: A TMA was constructed from 238 breast cancers with known HER2 status. Six punches were taken from different areas of each tumor, optimally from different paraffin blocks. HER2 stares was addressed immunohistochemically (HercepTest, DAKO) and by means of fluorescence in-situ hybridization (FISH, PathVysion, VYSIS/ABBOTT). Results: Concordant results were optalned from both conventional large sections and the diagnostic TMA in 97.9% of cases. Only 7 tumors showed discrepancies. Of these, 6 were borderline cases with HER2/Cenl7 ratio around 2.0, that had been interpreted differently in the large section and on the T M A analyses by chance. T h e remaining case was FISH negative/IHC positive on the large section, but both FISH and IHC positive on the TMA. Conclusions: A diagnostic application of TMAs is feasible at least for HER2 testing under the evaluated conditions (6 tissue cores per patient). More than 100 patients can be simultaneously analyzed on a single slide leading to a massive decrease of costs.
4 1'~/I / ~Ll" Prognostic value of the chemokine receptor CXCR4 in breast cancer R. DIALLO 1. , A. MI2rLLER2., R. VON WASIELEWSKP*, M. MENGEL 3, H.J. LUCK 4, B. HOMEY 5, R. KUBITZA 5, K.L. SCHAFER 1, H.E. GABBERT 1, C. POREMBA 1 (*These authors contributed equally to this work) 11nstitut ftir Pathologie 2Klinik fur Strahlentherapie, Universit~it Dtisseldorf 3Institut ftir Pathologie 4Franenklinik, MHH Hannover 5Hautklinik, Universit~it DUsseldorf
Aims: The chemokine receptor CXCR4 and its ligand CXCL12 (SDF-1) have recently been shown to be involved in breast cancer metastasis. The aim of this study was to analyze the prognostic impact of CXCR-4 expression in breast cancer.
306
Posters: Liver / Pathology - Research and Practice 200 (2004) 306-311
Methods: Tissue microarrays containing 390 samples of paraffinembedded breast carcinomas were used to analyze the expression of CXCR4 by immunohistochemical methods. Clinical and pathological data (TNM category, grade, overall survival, patient's age and others) were available for statistical analysis. The results were correlated with known prognostic markers such as estrogen (ER) and progesterone receptor, her-2/neu and Ki-67 (MIB 1). Results: CXCR4 expression was noted in 253 (64.8%) of the cases. A statistically significant negative correlation was found between CXCR4 expression and local relapse (P = 0.002) as well as distant metastasis (P = 0.04). CXCR4 expression was significantly correlated to a better overall survival (P = 0.01) in univariate, but not in multivariate, survival analysis. Moreover, there was a significant association between CXCR4- and ER-positivity (P = 0.004). Conclusions: These results demonstrate that the expression of CXCR4 is associated with a lower rate of relapse, a lower rate of distant metastases and a better outcome in breast cancer patients: These findings seem to be supported by a significant correlation between the CXCR4 expression and a positive ER status since ER ER positive breast cancers usually have a better prognosis.
ing solid tumors responded favorably to STI571, potentially due to the presence of KIT activating mutations. Methods: To investigate the epidemiology of KIT overexpression and mutations, a series of 1654 breast cancers was investigated. All tumors were analyzed by immunohistochemistry in a tissue microarray (TMA) format. Results: KIT expression was always seen in normal breast epithelium. However, cancer analysis revealed only 43 of 1654 (2.6%) KIT positive tumors. KIT expression was more frequent in medullary cancer (9 of 47 positive; 19.1%) than in any other histologic tumor subtype (p < 0.001). KIT expression was significantly associated with high tumor grade (p < 0.0001) but unrelated to pT and pN categories or patient survival. Mutation analysis of the exons 2, 8, 9, 11, 13, and 17 was negative in 10 KIT positive tumors. Conclusions: Overall, our data show that a high level of KIT expression occurs infrequently in breast cancer. KIT positive breast cancers may not reflect "KIT upregulation" as KIT is also expressed in normal breast epithelium. The lack of KIT mutations further argues against a therapeutic efficacy of STI571 in breast cancer.
195
Histopathological Results of The First Breast Cancer Screening Project in Germany
S. BIESTERFELD, R. DOETKOTTE, C. RUDLOWSKI 1
G. GOHLA, P. JOOST, U. SAUER, P. HANISCH, W. BOECKER 1, H. JUNKERMANN 2 , U. BONK
b c l - 2 - an independent prognostic marker in breast cancer
Institute of Pathology, University of Mainz and Department of Gynecology and Obstetrics 1, University of Heidelberg
Aims: bcl-2 has been discussed as prognostic factor in turnout pathology within the last years. However, up to now there is no clear evidence if also in breast cancer this factor is of univariate or even multivariate prognostic meaning. Furthermore, the results of various studies are contradictory. In our study, the prognostic influence of bcl-2 was tested on a series of 93 cases of breast cancer with a follow-up period of up to 11.5 years. Methods: bcl-2-immunohistochemistry was performed using a standard protocol. The number of immunoreactive cells and the staining intensity were evaluated semiquantitatively using a modified Remmele score (bcl-2-IRS). The results were correlated with clinical and morphological data. Results: The lymph node status (p = 0.0004), the bcl-2-IRS (p = 0.0004), the tumour size (p = 0.0084) and the turnout grading (p = 0.0133) revealed the highest univariate prognostic significance. In a multivariate Cox model the lymph node status (p = 0.0005) and the bcl-2-1RS (p = 0.0027) were entered with a high level of significance. The independent prognostic effect of bcl-2 was validated by Kaplan-Meier survival curves. Especially in the lymph node positive group patients with bcl-2-positive turnouts had a statistically significant better mean survival (7.6 vs. 3.5 years, p = 0.0002). In the lymph node negative group, there was a similar, but not significant trend (9.3 vs. 8.0 years, p > 0.05). Conclusions: bcl-2 proved to be a highly significant independent prognostic factor in breast cancer. Thus, this immunohistochemical marker can be recommended for routine application especially in lymph node positive cases.
196
197
Institut ffir Pathologie, ZKH Bremen-Nord u. ZKH St.-Jtffgenstrasse, Akad. Lehrkrankenhaus, Universitat Gtttingen aInstitut ftir Pathologic, Universitat Mtinster 2Mammographie Screening-Zentmm, Bremen
Aims: Presentation of the updated results and review of the histopathological findings of the first German breast cancer screening project. Methods: The first breast cancer screening project in Germany has been running in Bremen since 2001; the first screening round has now been completed. All women in Bremen between 50 and 70 years of age were offered mammography, and any abnormal findings were investigated by core biopsy. The biopsies were reviewed in the Pathology Dept. of the University Muenster and discussed at weekly multidisciplinary meetings. Lesions were classified using the 5-point, B classification scale as recommended by the EU. Results: To date, core biopsies have been obtained from nearly 500 women with abnormal mammographical findings with or without microcalcifications. Some 44% of these cases were classified as B5 (malignant), 48% as B 1 or B2 (benign) and 8% as B3 and B4 (atypia, probably benign, suspected malignancy). In only 10% of cases did the reviewing histopathologists not achieve consensus. Interestingly, disagreement only centered around atypical hyperplasias and papillary lesions. Conclusions: In this screening situation, the interobserver consensus amongst experienced breast pathologists was excellent. Disagreement was only reached where less well classified breast lesions were concerned; malignant lesions, which are of greater therapeutic concern, were rarely affected.
iiii!iiiiiPs iriiiiiii i Lii v ii
i !!!iili! iii! i ii iiiiii!i!ii¸iiiiiii!¸ iiii i
KIT (CDll7) positive breast cancers are infrequent and lack kit gene mutations R. SIMON, S. PANUSSIS, K. GLATZ, C. TAPIA, M. MIRLACHER, M. MIHATSCH, G. SAUTER
198 Electron Microscopic and Molecular Genetic Diagnostics in Hemochromatosis and Wilson's Disease L. JONAS, G. FULDA, M. STEINER 1, H. NIZZE 2
Institut ftir Pathologie, Universit~it Basel, Schweiz
Aims: KIT (CDl17) is a transmembrane tyrosine kinase representing a target for STI571 (Glivec®) therapy. Some KIT overexpress-
Elektronenmikroskopisches Zentrum,Universitat Rostock 11nstitut fiir Khnische Chemic und Pathobiochemie und 2Institut ftir Pathologic, Universitat Rostock
305
Results: ELISA and Western blot analysis revealed significantly re-
Methods: We investigated 2197 breast tumors in a tissue microar-
duced levels of the uPA protein in stable transfected and siRNAtransfected cells, as compared to non-transfected control samples. Real-time PCR analysis exhibited similar results at the mRNA levels. Incubation of uPA-silenced cells with recombinant HMW-uPA and ATF revealed an increase of proliferation activity. Addition of LMW-uPA did not alter proliferation activity in a significant manner. Conclusions: According to our results, uPA induces cell proliferation in breast cancer by binding to its specific receptor uPAR. Stimulation of proliferation is mediated via the growth factor-like domain of ATF. The catalytic domain of uPA is not involved in this process.
ray (TMA). All tumor samples were formalin fixed and paraffin embedded. For determination of Her-2 status we used commercial test kits for IHC (HercepTest TM, DAKO) and for FISH (reagent kit, Vyois). Results: The HER-2 IHC results differed greatly between 1551 tumors with interpretable HER-2 FISH signals and 405 breast cancers showing no FISH signals. FISH informative tumors had higher IHC scores than FISH non-informative tumors. FISH and IHC results were strongly associated (p < 0.0001) and all expected clinico-pathological associations could be found in our tumor set. Conclusion: Overall, the data show that not only FISH but also IHC results are dependent on good tissue quality for successful analysis. Poor tissue quality can be easily identified in FISH analyses because of a lack of hybridization signals. Inappropriate tissue handling is more dangerous in IHC because an artificial lack of staining can be regarded as "negative" result.
191 A novel diagnostic approach for the simultaneous study of HER2/neu overexpression and gene amplification in human breast cancers C. LOTTNER, S. SCHWARZ, R. JUNG, R. KNUCHEL 1, F. HOFSTADTER, G. BROCKHOFF
193
Institut ftir Pathologie, Universit~it Regensburg 11nstitut ftir Pathologie, Unlversit~itsklinikum der RWTH Aachen
R. SIMON, S. PANUSSIS, K. GLATZ, C. TAPIA, M. MIRLACHER, M. MIHATSCH, G. SAUTER
Aims: HER2/neu is overexpressed in 25% to 30% of human breast
Institut ftir Pathologie, Universit~it Basel, Schweiz
cancers. In order to increase the accuracy mid to improve the reproducibility of the HER2/neu diagnostics - immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) - we established a novel diagnostic approach based on the simultaneous detection of HER2/neu gene amplification via FISH and the correlated protein expression via fluorescent IHC on paraffin-embedded tissue. Methods: The HER2/neu oncogene, located at 17q21, was detected using the PathVysion HER2 DNA Probe Kit (VYSIS). The HER2/neu gene region was visualized with yellow fluorescence; the centromere 17 probe was green fluorescent. The HER2/neu protein expression (red fluorescence) was detected simultaneously using an epifluorescence microscope. Paraffin-embedded breast cancer cell lines were used as a reference for both gene amplification and protein expression. The diagnostic applicability was verified on primary breast cancer tissue sections. Results: The simultaneous detection of the HER2/neu receptor protein and gene copy number is reliably feasible in the multiparametric fluorescent approach. The immunohistochemical determination of the HER2/neu receptor status is in concordance with the FDA approved scoring, ranging from 0 to 3+ conventionally applied in the HercepTest (DAKO). With the novel approach gene copy number and protein content can be analyzed in the same cell. Conclusion: The combined fluorescent detection of protein expression and gene copy number on paraffin-embedded material improves the diagnostic value of HER2/neu and will be the basis for the development of an automated HER2/neu detection system.
192 HER-2 analysis in breast cancer: Reduced immunoreactivity in FISH non-informative cancer biopsies C. TAPIA, P. SCHRAML, R. SIMON, M. MIRLACHER, H. NOVOTNY, M.J. MIHATSCH, G. SAUTER Institut for Pathology, University of Basel, Basel
Aims: Due to the central role in predicting response to Herceptin TM and possibly also other anti cancer drugs, accurate and reproducible detection of the Her-2 status is important. Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) are the most commonly used methods for HER-2 analysis. In some cases FISH results are not interpretable for some reasons. To investigate a possible influence of tissue damage on the results of HER-2 IHC we compared the HER-2 IHC results obtained in tumors with and without interpretable FISH in breast cancer tissues.
Evaluation of tissue microarray based HER2 diagnosis
Aims: Numerous studies have demonstrated that tissue microarrays (TMAs) are adequately representative for their donor tissues in a research setting. But considering the increasing demand for predictive molecular tumor analysis, TMAs may also become relevant for diagnostic applications. Here, we evaluated the applicability of TMAs for HER2 diagnosis. Methods: A TMA was constructed from 238 breast cancers with known HER2 status. Six punches were taken from different areas of each tumor, optimally from different paraffin blocks. HER2 stares was addressed immunohistochemically (HercepTest, DAKO) and by means of fluorescence in-situ hybridization (FISH, PathVysion, VYSIS/ABBOTT). Results: Concordant results were optalned from both conventional large sections and the diagnostic TMA in 97.9% of cases. Only 7 tumors showed discrepancies. Of these, 6 were borderline cases with HER2/Cenl7 ratio around 2.0, that had been interpreted differently in the large section and on the T M A analyses by chance. T h e remaining case was FISH negative/IHC positive on the large section, but both FISH and IHC positive on the TMA. Conclusions: A diagnostic application of TMAs is feasible at least for HER2 testing under the evaluated conditions (6 tissue cores per patient). More than 100 patients can be simultaneously analyzed on a single slide leading to a massive decrease of costs.
4 1'~/I / ~Ll" Prognostic value of the chemokine receptor CXCR4 in breast cancer R. DIALLO 1. , A. MI2rLLER2., R. VON WASIELEWSKP*, M. MENGEL 3, H.J. LUCK 4, B. HOMEY 5, R. KUBITZA 5, K.L. SCHAFER 1, H.E. GABBERT 1, C. POREMBA 1 (*These authors contributed equally to this work) 11nstitut ftir Pathologie 2Klinik fur Strahlentherapie, Universit~it Dtisseldorf 3Institut ftir Pathologie 4Franenklinik, MHH Hannover 5Hautklinik, Universit~it DUsseldorf
Aims: The chemokine receptor CXCR4 and its ligand CXCL12 (SDF-1) have recently been shown to be involved in breast cancer metastasis. The aim of this study was to analyze the prognostic impact of CXCR-4 expression in breast cancer.
306
Posters: Liver / Pathology - Research and Practice 200 (2004) 306-311
Methods: Tissue microarrays containing 390 samples of paraffinembedded breast carcinomas were used to analyze the expression of CXCR4 by immunohistochemical methods. Clinical and pathological data (TNM category, grade, overall survival, patient's age and others) were available for statistical analysis. The results were correlated with known prognostic markers such as estrogen (ER) and progesterone receptor, her-2/neu and Ki-67 (MIB 1). Results: CXCR4 expression was noted in 253 (64.8%) of the cases. A statistically significant negative correlation was found between CXCR4 expression and local relapse (P = 0.002) as well as distant metastasis (P = 0.04). CXCR4 expression was significantly correlated to a better overall survival (P = 0.01) in univariate, but not in multivariate, survival analysis. Moreover, there was a significant association between CXCR4- and ER-positivity (P = 0.004). Conclusions: These results demonstrate that the expression of CXCR4 is associated with a lower rate of relapse, a lower rate of distant metastases and a better outcome in breast cancer patients: These findings seem to be supported by a significant correlation between the CXCR4 expression and a positive ER status since ER ER positive breast cancers usually have a better prognosis.
ing solid tumors responded favorably to STI571, potentially due to the presence of KIT activating mutations. Methods: To investigate the epidemiology of KIT overexpression and mutations, a series of 1654 breast cancers was investigated. All tumors were analyzed by immunohistochemistry in a tissue microarray (TMA) format. Results: KIT expression was always seen in normal breast epithelium. However, cancer analysis revealed only 43 of 1654 (2.6%) KIT positive tumors. KIT expression was more frequent in medullary cancer (9 of 47 positive; 19.1%) than in any other histologic tumor subtype (p < 0.001). KIT expression was significantly associated with high tumor grade (p < 0.0001) but unrelated to pT and pN categories or patient survival. Mutation analysis of the exons 2, 8, 9, 11, 13, and 17 was negative in 10 KIT positive tumors. Conclusions: Overall, our data show that a high level of KIT expression occurs infrequently in breast cancer. KIT positive breast cancers may not reflect "KIT upregulation" as KIT is also expressed in normal breast epithelium. The lack of KIT mutations further argues against a therapeutic efficacy of STI571 in breast cancer.
195
Histopathological Results of The First Breast Cancer Screening Project in Germany
S. BIESTERFELD, R. DOETKOTTE, C. RUDLOWSKI 1
G. GOHLA, P. JOOST, U. SAUER, P. HANISCH, W. BOECKER 1, H. JUNKERMANN 2 , U. BONK
b c l - 2 - an independent prognostic marker in breast cancer
Institute of Pathology, University of Mainz and Department of Gynecology and Obstetrics 1, University of Heidelberg
Aims: bcl-2 has been discussed as prognostic factor in turnout pathology within the last years. However, up to now there is no clear evidence if also in breast cancer this factor is of univariate or even multivariate prognostic meaning. Furthermore, the results of various studies are contradictory. In our study, the prognostic influence of bcl-2 was tested on a series of 93 cases of breast cancer with a follow-up period of up to 11.5 years. Methods: bcl-2-immunohistochemistry was performed using a standard protocol. The number of immunoreactive cells and the staining intensity were evaluated semiquantitatively using a modified Remmele score (bcl-2-IRS). The results were correlated with clinical and morphological data. Results: The lymph node status (p = 0.0004), the bcl-2-IRS (p = 0.0004), the tumour size (p = 0.0084) and the turnout grading (p = 0.0133) revealed the highest univariate prognostic significance. In a multivariate Cox model the lymph node status (p = 0.0005) and the bcl-2-1RS (p = 0.0027) were entered with a high level of significance. The independent prognostic effect of bcl-2 was validated by Kaplan-Meier survival curves. Especially in the lymph node positive group patients with bcl-2-positive turnouts had a statistically significant better mean survival (7.6 vs. 3.5 years, p = 0.0002). In the lymph node negative group, there was a similar, but not significant trend (9.3 vs. 8.0 years, p > 0.05). Conclusions: bcl-2 proved to be a highly significant independent prognostic factor in breast cancer. Thus, this immunohistochemical marker can be recommended for routine application especially in lymph node positive cases.
196
197
Institut ffir Pathologie, ZKH Bremen-Nord u. ZKH St.-Jtffgenstrasse, Akad. Lehrkrankenhaus, Universitat Gtttingen aInstitut ftir Pathologic, Universitat Mtinster 2Mammographie Screening-Zentmm, Bremen
Aims: Presentation of the updated results and review of the histopathological findings of the first German breast cancer screening project. Methods: The first breast cancer screening project in Germany has been running in Bremen since 2001; the first screening round has now been completed. All women in Bremen between 50 and 70 years of age were offered mammography, and any abnormal findings were investigated by core biopsy. The biopsies were reviewed in the Pathology Dept. of the University Muenster and discussed at weekly multidisciplinary meetings. Lesions were classified using the 5-point, B classification scale as recommended by the EU. Results: To date, core biopsies have been obtained from nearly 500 women with abnormal mammographical findings with or without microcalcifications. Some 44% of these cases were classified as B5 (malignant), 48% as B 1 or B2 (benign) and 8% as B3 and B4 (atypia, probably benign, suspected malignancy). In only 10% of cases did the reviewing histopathologists not achieve consensus. Interestingly, disagreement only centered around atypical hyperplasias and papillary lesions. Conclusions: In this screening situation, the interobserver consensus amongst experienced breast pathologists was excellent. Disagreement was only reached where less well classified breast lesions were concerned; malignant lesions, which are of greater therapeutic concern, were rarely affected.
iiii!iiiiiPs iriiiiiii i Lii v ii
i !!!iili! iii! i ii iiiiii!i!ii¸iiiiiii!¸ iiii i
KIT (CDll7) positive breast cancers are infrequent and lack kit gene mutations R. SIMON, S. PANUSSIS, K. GLATZ, C. TAPIA, M. MIRLACHER, M. MIHATSCH, G. SAUTER
198 Electron Microscopic and Molecular Genetic Diagnostics in Hemochromatosis and Wilson's Disease L. JONAS, G. FULDA, M. STEINER 1, H. NIZZE 2
Institut ftir Pathologie, Universit~it Basel, Schweiz
Aims: KIT (CDl17) is a transmembrane tyrosine kinase representing a target for STI571 (Glivec®) therapy. Some KIT overexpress-
Elektronenmikroskopisches Zentrum,Universitat Rostock 11nstitut fiir Khnische Chemic und Pathobiochemie und 2Institut ftir Pathologic, Universitat Rostock