106 research outputs found
Expression of minichromosome maintenance protein 2 as a marker for proliferation and prognosis in diffuse large B-cell lymphoma: a tissue microarray and clinico-pathological analysis-1
No full text<p><b>Copyright information:</b></p><p>Taken from "Expression of minichromosome maintenance protein 2 as a marker for proliferation and prognosis in diffuse large B-cell lymphoma: a tissue microarray and clinico-pathological analysis"</p><p>BMC Cancer 2005;5():162-162.</p><p>Published online 20 Dec 2005</p><p>PMCID:PMC1343577.</p><p>Copyright © 2005 Obermann et al; licensee BioMed Central Ltd.</p>Kaplan-Meier method). (IHC = immunohistochemistry
Expression of minichromosome maintenance protein 2 as a marker for proliferation and prognosis in diffuse large B-cell lymphoma: a tissue microarray and clinico-pathological analysis
No full textAbstract Background Minichromosome maintenance (MCM) proteins are essential for the initiation of DNA replication and have been found to be relevant markers for prognosis in a variety of tumours. The aim of this study was to assess the proliferative activity of diffuse large B-cell lymphoma (DLBCL) in tissue microarray (TMA) using one of the minichromosome maintenance proteins (Mcm2) and to explore its potential value to predict prognosis. Methods Immunohistochemistry for Mcm2 was performed on TMAs constructed from 302 cases of DLBCL. A monoclonal mouse antibody was used after heat induced antigen retrieval. Mcm2 expression was scored quantitatively. Positivity for Mcm2 was defined as presence of nuclear expression of Mcm2 in greater than or equal to 40 % of tumour cells. A statistical analysis was carried out of the association of Mcm2 and the clinico-pathological characteristics. Results Mcm2 expression was clearly evident in the nuclei of proliferating non-neoplastic cells and tumour cells. Positivity for Mcm2 was found in 46% (98/211) of analysable cases. A significant correlation existed between Mcm2 expression and presence of bulky disease (p = 0.003). Poor disease specific survival was observed in patients with DLBCL positive for Mcm2 expression in the univariate analysis (p = 0.0424). Conclusion Mcm2 expression can be used to assess tumour proliferation and may be useful as an additional prognostic marker to refine the prediction of outcome in DLBCL.</p
Expression of minichromosome maintenance protein 2 as a marker for proliferation and prognosis in diffuse large B-cell lymphoma: a tissue microarray and clinico-pathological analysis-0
No full text<p><b>Copyright information:</b></p><p>Taken from "Expression of minichromosome maintenance protein 2 as a marker for proliferation and prognosis in diffuse large B-cell lymphoma: a tissue microarray and clinico-pathological analysis"</p><p>BMC Cancer 2005;5():162-162.</p><p>Published online 20 Dec 2005</p><p>PMCID:PMC1343577.</p><p>Copyright © 2005 Obermann et al; licensee BioMed Central Ltd.</p>e zone are positive for Mcm2. Figure 1B: Immunohistochemical staining of Mcm2 in diffuse large B-cell lymphoma. This case is positive for Mcm2-expression with more than 40% of tumour cells expressing this marker
Abstract 2962: Mechanobiology of epithelia on native basement membrane and relevance for cancer invasion
No full textAbstract
The onset of metastasis occurs when cancer cells invade and breach the basement membrane (BM) that provides mechanical support to epithelial tissues. Yet, it remains unclear what triggers cancer cells to breach the BM, and how ‘triggered’ cells in fact breach the BM. We have established an in vitro assay using native BM interface for culturing epithelial cells. Using atomic force microscopy (AFM) with other high-resolution microscopies and TER (trans-epithelial resistance), we have correlated the mechano-cellular attributes of the BM/epithelium interface to its biochemical and structural properties. We demonstrated that the internal limiting membrane (ILM) isolated from human retinas acts as a native substrate for culturing epithelial cells in terms of BM composition, architecture and stiffness. These are required to act jointly in order to achieve apico-basal polarity, tissue barrier formation and stiffness properties of the epithelial layer similarly to secretory epithelia in vivo. The native BM serves several advantageous over reconstituted Matrigel, an ECM extracts that originates from mouse tumor ascites. Besides variations in thickness and biochemical composition, we find that Matrigel is mechanically 100-fold more compliant (i.e., softer) than native BMs. When tumorigenic variants of cells are used, we demonstrated that cancer cell invasion is associated with a decrease in cellular stiffness correlated to changes in cell and BM morphology. In addition, we showed that activation of ß1 integrin by the stiffness and architecture of the native alpha - 5 laminin chain has a key role, not only as previously thought for maintenance of cell polarity but also for the establishment of a physiological mechanophenotype. On the other hand it is well know that during cancer progression in vivo, cancer cells can perforate the BM using proteolysis. Whether stromal cells also play a role and what kind of role in this process is unclear. Therefore, we asked if carcinoma-associated fibroblasts (CAFs) isolated from cancer patients promote cancer cell invasion through a BM. In the presence of CAFs, moderately invasive cancer cells invade in a matrix metalloproteinase-independent manner. Using live imaging and atomic force microscopy, we showed that CAFs actively pull, stretch and soften the BM, forming gaps through which cancer cells can migrate. By exerting contractile forces, CAFs alter the organization and the physical properties of the BM, making it permissive for cancer cell invasion. Finally, we propose that, in addition to proteolysis, mechanical interactions between CAFs and BM represent an alternative mechanism of BM breaching. Given their mechano-biological relevance, native BMs allow us to further understand how mechanosignaling occurs between the epithelia and the surrounding stromal layers at the BM interface during cancer invasion and progression.
Note: This abstract was not presented at the meeting.
Citation Format: Marija Plodinec, Philipp Oertle, Daphne Assgeirson, Willi Halfter, Serenella Eppenberger Castori, Ellen C. Obermann, Alexandre Glentis, Roderick Y. LIM. Mechanobiology of epithelia on native basement membrane and relevance for cancer invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2962. doi:10.1158/1538-7445.AM2017-2962</jats:p
Cell cycle phase distribution analysis in chronic lymphocytic leukaemia: a significant number of cells reside in early G1-phase.
No full textBackground and Aims: Chronic lymphocytic leukaemia (CLL) is a frequent non-Hodgkin lymphoma characterised by a heterogeneous clinical course. Assessment of cell cycle phase kinetics might be important for prediction of clinical behaviour and prognosis. Methods: Distribution of neoplastic cells in CLL within the cell cycle was evaluated by determining the labelling indices (LI, i.e. percentage of positive cells) of markers specific for late G1-phase (cyclin E), S-phase (cyclin A), and G2/M-phase (cyclin B1), and Mcm2, a novel marker of proliferative potential, in a large cohort of patients (n = 79) using tissue microarray (TMA) technology. Utilising a combination of these markers, an algorithm was developed-subtracting the combined LIs of cyclin E, cyclin A and cyclin B1 from the LI of Mcm2-to determine the percentage of tumour cells residing in early G1-phase, which is probably a critical state for the malignant potential of CLL. Results: 27.11% of cells had acquired proliferative potential as indicated by expression of Mcm2. Only a small number of cells were found to be in late G1-phase (7.16%), S-phase (3.31%) or G2/M-phase (0.98%), while 15.66% of cells were considered to be in early G1-phase. Conclusion: Cell cycle phase distribution can easily be assessed by immunohistochemistry in routinely processed paraffin-embedded specimens. A large number of neoplastic cells in CLL have proliferative potential, with a significant sub-population residing in early G1-phase. Estimates of these cells may identify cases likely to exhibit a more aggressive biological behaviour and adverse clinical course
The clinical impact of p16 status in fine-needle aspirates of cervical lymph node metastasis of head and neck squamous cell carcinomas
No full textLymph node involvement is prognostically the most determinant clinical factor for patients with head and neck squamous cell carcinomas (HNSCCs). Ultrasound of the neck and fine-needle aspiration (FNA) cytology is one of the first diagnostic procedures and the most accurate diagnostic staging tool for the neck. Patients with HPV-positive oropharyngeal carcinomas (OPSCC) show a significantly better prognosis when compared with HPV-negative OPSCC. P16 overexpression is accepted as surrogate marker for HPV-positive in OPSCC. These HPV/p16-positive OPSCC are localized either in the palatal tonsils or the base of tongue and frequently present with lymph node metastases. We analyzed the correlation and reliability of p16 expression of the FNA of the lymph node metastasis with the immunohistochemical expression of p16 of the same lymph node metastasis and its corresponding primary tumor, as it could be of importance for determining the localization and different prognosis of the primary tumor. 54 HNSCC patients were evaluated, p16 expression of the primary tumors and their lymph node metastases correlated precisely. In 25 of the 54 HNSCC patients, a FNA of the lymph node metastases was taken before the treatment. The positive cytological and immunohistochemical p16 staining correlated exactly. Of the 17 histologically p16-negative lymph node metastases 15 FNA were p16-negative, whereas two samples were p16-positive. In our view, a cytological p16 analysis of cervical lymph node metastasis can facilitate the correct localization of the primary tumor and discriminate reliably HPV-positive OPSCC from HPV-negative HNSCC with their significantly diverse prognosis
How reliable is Ki-67 immunohistochemistry in grade 2 breast carcinomas? A QA study of the Swiss Working Group of breast- and gynecopathologists
No full textAdjuvant chemotherapy decisions in breast cancer are increasingly based on the pathologist's assessment of tumor proliferation. The Swiss Working Group of Gyneco- and Breast Pathologists has surveyed inter- and intraobserver consistency of Ki-67-based proliferative fraction in breast carcinomas.
Methods
Five pathologists evaluated MIB-1-labeling index (LI) in ten breast carcinomas (G1, G2, G3) by counting and eyeballing. In the same way, 15 pathologists all over Switzerland then assessed MIB-1-LI on three G2 carcinomas, in self-selected or pre-defined areas of the tumors, comparing centrally immunostained slides with slides immunostained in the different laboratoires. To study intra-observer variability, the same tumors were re-examined 4 months later.
Results
The Kappa values for the first series of ten carcinomas of various degrees of differentiation showed good to very good agreement for MIB-1-LI (Kappa 0.56–0.72). However, we found very high inter-observer variabilities (Kappa 0.04–0.14) in the read-outs of the G2 carcinomas. It was not possible to explain the inconsistencies exclusively by any of the following factors: (i) pathologists' divergent definitions of what counts as a positive nucleus (ii) the mode of assessment (counting vs. eyeballing), (iii) immunostaining technique, and (iv) the selection of the tumor area in which to count. Despite intensive confrontation of all participating pathologists with the problem, inter-observer agreement did not improve when the same slides were re-examined 4 months later (Kappa 0.01–0.04) and intra-observer agreement was likewise poor (Kappa 0.00–0.35).
Conclusion
Assessment of mid-range Ki-67-LI suffers from high inter- and intra-observer variability. Oncologists should be aware of this caveat when using Ki-67-LI as a basis for treatment decisions in moderately differentiated breast carcinomas
Targetable molecular pathways in classical Hodgkin's lymphoma
No full textINTRODUCTION: most patients with classical Hodgkin's lymphoma (cHL) are cured by stage-adapted multimodal regimens. However, some will suffer from refractory disease or experience a relapse. Furthermore, late toxicity due to aggressive chemotherapy and/or radiotherapy has become an increasing problem in long-term survivors. Special situations, such as cHL in a post-transplant setting and patients not able to tolerate standard therapy, are also challenging. Targeting molecular pathways could be a way to find solutions for these varied aspects. AREAS COVERED: research undertaken by leading experts in the field of cHL is summarized. The literature search encompasses all data available via PubMed or published (pre-)clinical trials until August 2010. We discuss the crucial molecular pathways in cHL, novel agents that may be utilized to interact with these pathways, and insights into the results of current clinical trials utilizing these novel therapeutics. EXPERT OPINION: the most important oncogenic pathways in cHL are loss of B-cell identity by the neoplastic cells, activation of the NF-?B pathway, and constitutive activation of the JAK2-STAT-pathway. Both monoclonal antibodies and small-molecule inhibitors are potentially useful agents to target these pathways
Prediction of outcome in patients with low-grade squamous intraepithelial lesions by fluorescence in situ hybridization analysis of human papillomavirus, TERC, and MYC
No full textBACKGROUND
Cytology is an excellent method with which to diagnose preinvasive lesions of the uterine cervix, but it suffers from limited specificity for clinically significant lesions. Supplementary methods might predict the natural course of the detected lesions. The objective of the current study was to test whether a multicolor fluorescence in situ hybridization (FISH) assay might help to stratify abnormal results of Papanicolaou tests.
METHODS
A total of 219 liquid-based cytology specimens of low-grade squamous intraepithelial lesions (LSIL), 49 atypical squamous cells of undetermined significance (ASCUS) specimens, 52 high-grade squamous intraepithelial lesion (HSIL) specimens, and 50 normal samples were assessed by FISH with probes for the human papillomavirus (HPV), MYC, and telomerase RNA component (TERC). Subtyping of HPV by polymerase chain reaction (PCR) was performed in a subset of cases (n=206).
RESULTS
There was a significant correlation found between HPV detection by FISH and PCR (P2 signals in>10% of cells) prevailed in 43% of ASCUS specimens and was more frequent in HSIL (85%) than in LSIL (33%) (HSIL vs LSIL: P<.0001). Increased TERC gene copy number was significantly correlated with progression of LSIL (P<.01; odds ratio, 7.44; area under the receiver operating characteristic curve, 0.73; positive predictive value, 0.30; negative predictive value, 0.94) CONCLUSIONS: The detection of HPV by FISH analysis is feasible in liquid-based cytology and is significantly correlated with HPV analysis by PCR. The analysis of TERC gene copy number may be useful for risk stratification in patients with LSIL
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