Verhandlungen der Deutschen Gesellschaft fur Pathologie最新文献

{"title":"[Herceptin therapy in breast cancer: new indication?].","authors":"Annette Lebeau","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>HER-2 belongs to a family of four transmembrane receptor tyrosine kinases that mediate growth, differentiation and survival of cells. HER-2 overexpression and amplification occurs in approximately 15 to 25 % of breast cancers and is associated with aggressive tumour behaviour. Herceptin (trastuzumab), a humanized monoclonal antibody directed against the extracellular domain of the HER-2 receptor, has been shown to have clinical activity in HER-2-positive advanced breast cancer when administered alone or in combination with chemotherapy. It has been approved for HER-2-positive metastatic breast cancer by the United States Food and Drug Administration in 1998 and in the countries of the European Union in 2000. Recently, promising results of the four randomized international multicenter trials evaluating the therapeutic benefit of Herceptin in the adjuvant treatment of HER-2-positive primary breast cancer have been reported. Data of the first planned interim analysis of the studies showed significantly improved disease-free survival in patients assigned to one year of Herceptin compared to the control groups even after short term follow up. These results caused an immediate wave of demand for Herceptin in adjuvant therapy. Results of these studies are critically reviewed. Furthermore, the available preliminary results from studies using Herceptin in the primary (neoadjuvant) therapy of HER-2-positive breast cancer are addressed and possible implications for HER-2 testing are discussed.</p>","PeriodicalId":76792,"journal":{"name":"Verhandlungen der Deutschen Gesellschaft fur Pathologie","volume":"90 ","pages":"99-106"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40970774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Use and problems of the TNM classification].","authors":"Christian Wittekind","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The TNM system is the most important classification for describing the anatomical extent of tumors. The residual tumor classification describes the completeness of tumor removal. Although the definitions of both systems seem clear and precise, the daily work offers questions on how to use special situations. Despite the importance of the TNM- and residual tumor classification in planning clinical management before and after treatment, the misinterpretations and inconsistencies in application diminish or abrogate their clinical utility. Some of the questions and problems will be addressed in this contribution.</p>","PeriodicalId":76792,"journal":{"name":"Verhandlungen der Deutschen Gesellschaft fur Pathologie","volume":"90 ","pages":"142-50"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40970780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"C-kit expression in high-risk breast cancer subgroup treated with high-dose or conventional dose-dense chemotherapy.","authors":"R Diallo,&nbsp;E Ting,&nbsp;O Gluz,&nbsp;A Herr,&nbsp;G Schütt,&nbsp;H Geddert,&nbsp;S Mohrmann,&nbsp;H E Gabbert,&nbsp;U Nitz,&nbsp;C Poremba","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The proto-oncogene c-kit is known to be expressed in poorly differentiated breast cancer. In this study, we retrospectively evaluated the prognostic and predictive impact of c-kit in a high risk subgroup of breast cancer patients (>9 axillary node metastases) who received high-dose (HDCT) or dose-dense (DDCT) conventional chemotherapy and correlated these findings with the expression of the basal-type markers CK5 and CK 17, estrogen (ER) and progesterone (PR) receptor, Her-2/neu and MIB 1. C-kit, CK5, CK17, ER, PR, Her-2/neu and MIBI expression was evaluated immunohistochemically using tissue microarrays containing breast cancer samples from 236 patients who were randomized to the WSG AM01 trial (median follow-up of 60 months). There was a significant overall survival (OS) benefit for patients receiving HDCT compared to DDCT (p = 0.027). C-KIT expression was found in 12 % of all breast cancers and correlated with a poorer OS in multivariate analysis (p = 0.051). Furthermore, c-kit correlated with high grade (p = 0.019), CK5- and CK17-positivity (p <0.0001 and p = 0.001, respectively) and ER- and PR-negativity (p = 0.04 and p = 0.008, respectively). In contrast to CK5 and CK17, patients with c-kit positive breast cancers revealed no benefit from high-dose chemotherapy. These findings underline that c-kit expression represents an independent negative prognostic marker in high-risk breast cancer. Correlation with CK5 +/CK17+ and ER-/PR-suggests that c-kit positive carcinomas are at least partly of basal-type.</p>","PeriodicalId":76792,"journal":{"name":"Verhandlungen der Deutschen Gesellschaft fur Pathologie","volume":"90 ","pages":"177-85"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40972860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Her-2/neu analysis--new data?].","authors":"T Gaiser,&nbsp;M Hofmann,&nbsp;O Stoss,&nbsp;T Henkel,&nbsp;J Rüschoff","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Her-2 status determination is an essential prerequisite before considering patient eligibility for treatment with trastuzumab. Currently the most common techniques to assess Her-2 status in routine practice are immunohistochemistry (IHC) and dual color FISH for receptor expression and gene amplification analysis, respectively. Despite both methods are well-established in breast cancer there are a variety of yet unsolved questions: 1. Do we really need IHC since interlab variation is still quite high (up to 30%)? 2. Are FISH and CISH equivalent techniques? 3. Are there any precautions to be taken if Her-2 is tested in non-breast cancer samples? 4. What is the value of Her-2 status in blood serum (ELISA)? 5. Do we get better response prediction if new Her2 antibodies, other techniques such as quantitative (q) RT-PCR or multiparameter assays according to downstream signalling pathways are applied? 6. Is Her-2 status still predictive when other therapeutic antibodies than trastuzumab (e. g. pertuzumab) or kinase inhibitors (e. g. lapatinib) are used? These questions will be discussed under the review of the recent literature and under own experiences obtained either by centralized Her-2 assessment in a variety of breast and non-breast cancer therapy studies and within international ring studies between reference labs from Australia (M. Bilous), Canada (W. Hanna), France (F. Penault-Llorcoa), Great Britain (M. Dowsett), Japan (R. Y. Osamura), and Netherlands (M. v. d. Vijver) in which we participated.</p>","PeriodicalId":76792,"journal":{"name":"Verhandlungen der Deutschen Gesellschaft fur Pathologie","volume":"90 ","pages":"107-13"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40970775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Preoperative chemotherapy in breast cancer and the development of new predictive markers].","authors":"C Denkert,&nbsp;O Schickling,&nbsp;G von Minckwitz","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Neoadjuvant chemotherapy provides today a valid option for many patients with primary breast cancer. For evaluation of treatment response as well as for biomarker studies for prediction of response, an efficient collaboration between pathologists and gynaecological oncologists is essential. This report reflects aims and indication according to the current opinion, describes advantages and disadvantages in comparison to the conventional adjuvant approach and provides guidelines on how to conduct the whole treatment concept of neoadjuvant therapy. Current and projected study concepts of preoperative and following postsurgical treatments in Germany are introduced. While the basic principles of histopathological evaluation of tumour specimens from neo-adjuvant breast cancer studies are similar to conventional surgical therapy, some aspects of histopathological management are of special importance in these studies.</p>","PeriodicalId":76792,"journal":{"name":"Verhandlungen der Deutschen Gesellschaft fur Pathologie","volume":"90 ","pages":"114-23"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40970776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Role of predictive pathology in oncology--example of new therapies targeting EGFR].","authors":"Arndt Hartmann","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>New cancer-specific therapies are based on specific molecular alterations of malignant tumors which are targeted by small inhibitory molecules or specific antibodies. During the development of these agents potential molecular targets are characterized for their expression and importance for pathogenesis and clinical course of the disease. Frequently the assumption is made that the degree of expression of the target protein or the molecular alteration of the target gene allows a prediction if a certain patient will profit from the therapy against this specific protein or not. The first example was that breast cancer patients with overexpression and/or amplification of Her-2 respond to a Her-2-specific antibody (Herceptin) therapy. The expression or activation of the Epidermal Growth Factor Receptor (EGFR, Her-1) are altered in many epithelial tumours and clinical studies indicate that they have important roles in tumor aetiology and progression. Several EGFR-specific monoclonal antibodies and specific tyrosine kinase inhibitors were developed in the last years. Cetuximab is approved for the treatment of metastatic colorectal cancer and advanced squamous cell carcinoma of the head and neck and is investigated in numerous trials for other tumors. The expression of EGFR in the tumor was a prerequisite for the therapy in the first trials, giving the pathologist a central role in treatment decision. However, recent data clearly demonstrate that the degree of EGFR expression does not correlate with therapy response. Therefore a therapy should be not denied to a individual patient solely because of lack of EGFR expression in the tumor. Tyrosine kinase inhibitors (e. g. Gefitinib, Erlotinib) are effective in the treatment of non small cell lung cancer and also investigated in ongoing trials in many cancer types. The correlation of therapy response with both specific molecular alterations (EGFR tyrosine kinase domain mutations) and clinicopathological features (Asian ethnicity, women, non-smokers, bronchioloalveolar differentation) is a good example of the potential role of predictive molecular pathology in the future.</p>","PeriodicalId":76792,"journal":{"name":"Verhandlungen der Deutschen Gesellschaft fur Pathologie","volume":"90 ","pages":"128-35"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40970778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Mutations of the tumor suppressor gene SOCS-1 in classical Hodgkin lymphoma are frequent and associated with nuclear phospho-STAT5 accumulation].","authors":"M A Weniger,&nbsp;I Melzner,&nbsp;C K Menz,&nbsp;S Wegener,&nbsp;A J Bucur,&nbsp;K Dorsch,&nbsp;T Mattfeldt,&nbsp;T F E Barth,&nbsp;P Möller","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Aims: </strong>Suppressors of cytokine signaling (SOCS) negatively regulate Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling involved in proliferation, survival, and apoptosis. We previously showed a loss of SOCS-1 function due to deleterious mutations in a major subset of mediastinal B-cell lymphoma (MBL). In MBL cell lines this leads to retarded JAK2 degradation and sustained phospho-STAT5 action results in enhanced DNA binding of phospho-STAT5.</p><p><strong>Methods: </strong>To investigate the SOCS-1 gene we laser-microdissected Hodgkin-and Reed-Sternberg (HRS) cells of 19 classical Hodgkin lymphoma (cHL) and performed sequencing analysis. To assess phospho-STAT5 status immunohistochemistry on the corresponding paraffin-embedded cHL tumor tissue was done.</p><p><strong>Results: </strong>We detected mutations of the SOCS-1 gene in HRS cells of 8 of 19 cHL samples and in 3 of 5 cHL-derived cell lines. Moreover, we found a significant association between mutated SOCS-1 of isolated HRS cells and nuclear phospho-STAT5 accumulation in HRS cells (P <0.01).</p><p><strong>Conclusions: </strong>In conclusion, these findings support the concept that MBL and cHL share overlapping features and that defective tumor suppressor gene SOCS-1 triggers an oncogenic pathway operative in both lymphomas.</p>","PeriodicalId":76792,"journal":{"name":"Verhandlungen der Deutschen Gesellschaft fur Pathologie","volume":"90 ","pages":"210-5"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40972864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Hepatocellular carcinoma: novel molecular aspects for differential diagnosis and therapy].","authors":"M A Kern,&nbsp;P Schirmacher","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide and shows increasing incidence. Multimodal strategies against HCC include primary (e.g. immunisation) and secondary (e. g. antiviral therapy) prevention, surgical approaches, novel specific systemic therapies (targeted therapy), and the treatment of comorbidity (cirrhosis). New molecular approaches are currently under development and tackle several specific targets. In this context pathology is needed in many aspects: experimental strategies, development of valid tumor-relevant diagnostic tests as well as morphological evaluation in the context of clinical studies and finally in routine diagnosis.</p>","PeriodicalId":76792,"journal":{"name":"Verhandlungen der Deutschen Gesellschaft fur Pathologie","volume":"90 ","pages":"85-98"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40972953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Cytomics and receptor interaction].","authors":"Gero Brockhoff","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The system of erbB-receptor-tyrosine-kinases (RTKs) appears considerable complex because four erbB-receptors crossactivate each other via homo- and heterointeraction upon ligand binding. This complexicity is additionally elevated by scores of corresponding growth factors with unique binding- and activation-specificity. The total receptor-ligand system provides the basis for intracellular signal- diversity and -specificity. Significant oncological importance is attributed to the family of erbB-RTKs, which are known to cause and contribute to carcinogenesis, tumor progression, invasion, metastasis, e. g. based on uncontrolled cell growth and cell proliferation. The detection of erbB-receptor gene amplification or corresponding protein overexpression is well established in tumor diagnosis and an essential element for therapy decision. However, the assessment of the coexpression profile of erbB-receptors and the presence or absence of growth factors has not been implemented into pathological diagnosis so far. Cytomics represents a novel discipline in systems-biology. It is dedicated to understand and resolve biocomplexicity of cells, cellular components, and cell-systems. Understanding the function of the integrated erbB-receptor-system on a cytomic level will facilitate to more precisely follow-up the course of disease and thereby to elevate prognosis to the level of individual prediction. A system biological approach should involve the analysis of molecular function and dynamics on a single cell level and thereby is expected to characterize the disease in terms of a given molecular equivalent. Additionally, new and highly specific drug targets are likely to be identified. The comprehensive analysis of the complex molecular erbB-receptor system will enable to stratify tumor patients more precisely and simultaneously to specify erbB-receptor based therapeutic strategies in terms of individualized medicine.</p>","PeriodicalId":76792,"journal":{"name":"Verhandlungen der Deutschen Gesellschaft fur Pathologie","volume":"90 ","pages":"31-8"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40973008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Salivary duct carcinomas comprise phenotypically and genotypically diverse high grade neoplasms].","authors":"Daniela Hungermann,&nbsp;Eberhard Korsching,&nbsp;Horst Bürger,&nbsp;Kerstin Röser,&nbsp;Thomas Löning,&nbsp;Hermann Herbst","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Salivary duct carcinomas (SDC) are high grade neoplasms morphologically reminiscent of breast ductal carcinomas. Whereas the latter are well characterized, the body of immunophenotypic and cytogenetic data on SDC is limited. We studied 23 SDC by conventional histology, immunohistology, in situ hybridization, and comparative genomic hybridization (CGH). Data were subjected to biomathematical analysis in comparison to previously characterized breast ductal carcinomas in situ and invasive ductal carcinoma cases. Most SDC stained for cytokeratins (Ck) Ck 8/18 (77 %) or Ck 5/6 (30 %), 30 % of cases expressed the androgen receptor (AR), 14 cases (63 %) expressed c-erbB2, and one case stained for prostate specific antigen. Except for two cases, Ck 8/18 and Ck 5/6 were not coexpressed. Ck 8/18 expression positively correlated with presence of c-erbB2 and AR. At variance, Ck 5/6 correlated positively with p63 and inversely with both AR and c-erbB2 expression. Ck 5/6 and p 63 co-expression was also found in a distinct population of ductal epithelial cells of normal salivary glands. CGH analysis of SDC revealed increasing numbers of alterations in correlation with advanced diseases, but no recurrent alterations. Cluster analysis of phenotypic and genotypic markers assigned both salivary and breast carcinomas to numerous clusters independent of the primary tumour site. Although undistinguishable by conventional histology, SDC are heterogeneous, comprising at least two immunophenotypically distinct subgroups of neoplasms. Cluster analysis suggests several distinct patterns of gene expression common to both primary sites explaining morphologic parallels between SDC and high grade breast cancer.</p>","PeriodicalId":76792,"journal":{"name":"Verhandlungen der Deutschen Gesellschaft fur Pathologie","volume":"90 ","pages":"168-76"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40972859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}