			Home About us Contact

Tumour Grade (tumour + grade)

Distribution by Scientific Domains

Medical Sciences	96%

Distribution within Medical Sciences

Pathology	25%
Surgery & Surgical Specialties	18%

Selected Abstracts

Relationship between hormone receptor status and tumour size, grade and comedo necrosis in ductal carcinoma in situ,

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 4 2005
N. L. P. Barnes
Background: Results of the National Surgical Adjuvant Breast Project B-24 trial indicate that adjuvant tamoxifen therapy is of benefit only in oestrogen receptor (ER)- positive ductal carcinoma in situ (DCIS). In the UK, ER status is not routinely determined in DCIS. The aim of this study was to assess the ER status in women with DCIS to determine whether any clinicopathological factors could predict positivity instead of immunohistochemical assessment. Methods: The ER and progesterone receptor (PR) status of consecutive women diagnosed with DCIS during 2001 and 2002 was determined by immunohistochemistry. Results: One hundred and nineteen tumours diagnosed between 2001 and 2002 were analysed; 73·0 per cent were ER positive and 61·1 per cent were PR positive. PR positivity was associated with ER positivity (P < 0·001). Increasing tumour grade correlated with a decrease in ER and PR positivity (both P = 0·002). Comedo necrosis was associated with ER negativity (P = 0·026), PR negativity (P = 0·033) and a lower percentage of ER expression in ER-positive tumours (mean(s.d.) 82(27) versus 93(10) per cent; P = 0·021). Conclusion: Tumour grade and comedo necrosis were not strong enough predictors to be used as surrogates for immunohistochemical assessment. ER status should be determined before commencing endocrine therapy. Copyright © 2005 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source]

Amplified in breast cancer 1 expression in breast cancer

HISTOPATHOLOGY, Issue 6 2008
M A Thorat
Aims:, The amplified in breast cancer 1 (AIB1), steroid receptor co-activator family member, acts as an oestrogen receptor (ER) co-activator. Acting with HER-2, it is thought to play a role in endocrine resistance by facilitating ER,growth factor crosstalk. The aim was to analyse AIB1 expression by immunohistochemistry and study its correlations with other prognostic variables in breast cancer and its effect on survival. Methods:, A tissue microarray comprising tumours from 438 patients with 15.4 years' median follow-up was used. Interpretable AIB1 expression obtained in 395 patients was analysed along with other prognostic factors in breast cancer. Results:, AIB1 expression scores ranged from 0 to 30; positive AIB1 expression (score > 14) was seen in 146/395 breast cancers; it correlated negatively with ER (P = 0.003) and progesterone receptor (PR) (P = 0.007), and positively with HER-2 (P = 0.005) and tumour grade (P = 0.014). It did not correlate with nodal status (P = 0.437). Among ER+ patients, AIB1 expression showed a trend towards loss of PR expression (29% versus 20%; P = 0.14). AIB1 did not predict survival on univariate or multivariate analysis. Conclusions:, AIB1 expression correlates with HER-2 expression in breast cancer and shows a trend of association with loss of PR expression in ER+ tumours. Our study supports the postulated role of AIB1 in ER,growth factor interactions. [source]

Model for end-stage liver disease (MELD) score, as a prognostic factor for post-operative morbidity and mortality in cirrhotic patients, undergoing hepatectomy for hepatocellular carcinoma

HPB, Issue 4 2009
Spiros G. Delis
Abstract Background/aims:, To evaluate the ability of the model for end-stage liver disease (MELD) in predicting the post-hepatectomy outcome for hepatocellular carcinoma (HCC). Methods:, Between 2001 and 2004, 69 cirrhotic patients with HCC underwent hepatectomy and the results were retrospectively analysed. MELD score was associated with post-operative mortality and morbidity, hospital stay and 3-year survival. Results:, Seventeen major and 52 minor resections were performed. Thirty-day mortality rate was 7.2%. MELD , 9 was associated with no peri-operative mortality vs. 19% when MELD > 9 (P < 0.02). Overall morbidity rate was 36.23%; 48% when MELD > 9 vs. 25% when MELD , 9 (P < 0.02). Median hospital stay was 12 days [8.8 days, when MELD , 9 and 15.6 days when MELD > 9 (P = 0.037)]. Three-year survival reached 49% (66% when MELD , 9; 32% when MELD > 9 (P < 0.01). In multivariate analysis, MELD > 9 (P < 0.01), clinical tumour symptoms (P < 0.05) and American Society of Anesthesiologists (ASA) score (P < 0.05) were independent predictors of peri-operative mortality; MELD > 9 (P < 0.01), tumour size >5 cm (P < 0.01), high tumour grade (P = 0.01) and absence of tumour capsule (P < 0.01) were independent predictors of decreased long-term survival. Conclusion:, MELD score seems to predict outcome of cirrhotic patients with HCC, after hepatectomy. [source]

Osteoprotegerin (OPG),a potential new role in the regulation of endothelialcell phenotype and tumour angiogenesis?

INTERNATIONAL JOURNAL OF CANCER, Issue 8 2006
Simon S. Cross
Abstract The progression of cancer depends on the establishment of a tumour blood supply, and therefore tumour angiogenesis has been identified as a major target for new anticancer agents. Recent reports have suggested that osteoprotegerin (OPG) is involved in the control of endothelial cell survival through the inhibition of the activity of tumour necrosis factor- (TNF) related apoptosis-inducing ligand (TRAIL). The role of OPG in human tumour development and angiogenesis is currently unknown. In the present study we demonstrate the ability of OPG to support endothelial cell survival, as well as the formation of cord-like structures in vitro using a matrigel tubule formation assay. Investigation of various human cancers demonstrated endothelial OPG expression in 59% of malignant tumours (n = 512), but in contrast, OPG was absent in endothelial cells associated with benign tumours and normal tissues (n = 178). In a series of 400 breast tumours, endothelial OPG expression was associated with high tumour grade and certain histological types. Our data show a clear separation in endothelial OPG expression between malignant tumours and nonmalignant tissues, supporting a potential biological role for this molecule in the development and/or maintenance of the tumour vasculature. This is the first study to report the proangiogenic effects of OPG in vitro, as well as correlating expression of OPG by tumour endothelial cells with clinicopathological data in human tumours. © 2005 Wiley-Liss, Inc. [source]

Regulatory T cells and their prognostic value for patients with squamous cell carcinoma of the head and neck

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1-2 2010
Jan Boucek
Abstract Regulatory T cells (Treg) are important regulators of anti-cancer immune responses, and an increase in Treg frequency was observed in the blood of cancer patients. Blood samples from 112 patients with head and neck squamous cell carcinoma antigen (HNSCC) were obtained at the time of tumour diagnosis, and lymphocyte subpopulations (CD3+; CD3,CD16+CD56+; CD4+; CD8+; CD19+; CD4+CD45RA+) with emphasis on Treg counts (CD3+CD4+CD25+), complete blood count and tumour markers (squamous cell carcinoma [SCC]; CEA; ,-1-antitrypsin [AAT]; Cyfra 21,1; C-reactive protein [CRP]) were analysed. The data were grouped according to TNM classification, and their significance for the course of the disease at an interval of 1 year after the end of the therapy was determined. The percentage of CD8+ cells increased and the CD/D8 ratio decreased with tumour grade. The ratio of B lymphocytes decreased in patients with locoregional metastases (11.25%versus 9.22%). Treg (15.2%) and CD4+ cells (45.3%) increased, while NK cells (11.8%) decreased in HNSCC patients compared to controls (9.0%, 38.1% and 15.8%, respectively). The data obtained at time of diagnosis were used to assess the significance of tumour markers (SCC, Cyfra 21,1 and AAT) for evaluation of prognosis. The erythrocyte counts (4.64 × 1012/l versus 4.45 × 1012/l) and haemoglobin levels (14.58 g/dl versus 14.05 g/dl) decreased, while Treg counts (8.91%versus 15.70%) increased in patients with early recurrence. Our results show that examination of these parameters could be helpful for prognostication in HNSCC patients and aid improvement of treatment strategy. [source]

Stromal laminin chain distribution in normal, hyperplastic and malignant oral mucosa: relation to myofibroblast occurrence and vessel formation

JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 4 2010
Marcus Franz
J Oral Pathol Med (2010) 39: 290,298 Background:, The contribution of stromal laminin chain expression to malignant potential, tumour stroma reorganization and vessel formation in oral squamous cell carcinoma (OSCC) is not fully understood. Therefore, the expression of the laminin chains ,2, ,3, ,4, ,5 and ,2 in the stromal compartment/vascular structures in OSCC was analysed. Methods:, Frozen tissue of OSCC (9× G1, 24× G2, 8× G3) and normal (2×)/hyperplastic (11×) oral mucosa was subjected to laminin chain and ,-smooth muscle actin (ASMA) immunohistochemistry. Results were correlated to tumour grade. The relation of laminin chain positive vessels to total vessel number was assessed by immunofluorescence double labelling with CD31. Results:, Stromal laminin ,2 chain significantly decreases and ,3, ,4, ,5 and ,2 chains and also ASMA significantly increase with rising grade. The amount of stromal ,3, ,4 and ,2 chains significantly increased with rising ASMA positivity. There is a significant decrease in ,3 chain positive vessels with neoplastic transformation. Conclusions:, Mediated by myofibroblasts, OSCC development is associated with a stromal up-regulation of laminin isoforms possibly contributing to a migration promoting microenvironment. A vascular basement membrane reorganization concerning ,3 and ,2 chain laminins during tumour angioneogenesis is suggested. [source]

Expression of vascular endothelial growth factor-C correlates with the lymphatic microvessel density and the nodal status in oral squamous cell cancer

JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 8 2003
Roland Sedivy
Abstract Background:, The cause of preferential metastatic spreading to cervical lymph nodes in oral squamous cell cancer (SCC) is not quite clear. As the density of microvessels may influence the metastatic behaviour, we were interested in how the density of blood/lymphatic microvessels are related to primary SCC and the clinical course of the disease. Methods:, Lymphatic and blood microvessels of 28 patients with oral SCC were identified immunohistochemically by antibodies against podoplanin and CD34, respectively. Lymphatic microvessel density (LVD) and blood microvessel density (MVD), and the expression of VEGF-C were determined. These findings were compared with the long-term clinicopathological data of the patients. Results:, LVD and MVD were significantly higher than in control tissues. The amount of lymphatic microvessels correlated positively with the expression of VEGF-C, the tumour grade, the nodal status and with later appearing metastasis. The latter three parameters, however, did not influence the clinical course of the disease. Conclusions:, VEGF-C expression in oral SCC triggers lymphatic angiogenesis, which may result in a higher risk for cervical lymph node metastasis. The angiogenetic effect of VEGF-C may also favour the onset of late lymphatic and haematogenous metastases. [source]

Deranged expression of the E-cadherin/,-catenin complex and the epidermal growth factor receptor in the clinical evolution and progression of oral squamous cell carcinomas

JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 8 2002
Agnes Bánkfalvi
Abstract Background:, Deranged expression and function of the E-cadherin/,-catenin (E-cad/,-cat) complex and the epidermal growth factor receptor (EGFR) have been implicated in the development and progression of carcinomas. Methods:, To estimate the role of these molecules in oral cancer, we investigated 75 primary oral squamous cell carcinomas (OSCCs) with adjacent normal and/or dysplastic mucosa, 30 paired metastases and 12 recurrences by immunohistochemistry. Results:, All three molecules were constitutionally expressed in the basal/parabasal layers of tumour adjacent ,normal' epithelium, in contrast to a significant increase of EGFR and heterogeneous expression of E-cad/,-cat in dysplasia. In OSCCs, over-expression of EGFR correlated significantly with lower tumour grade and poor prognosis, loss of E-cad was a significant marker for shortened survival, reduced ,-cat staining was a predictive marker for lymph node metastasis. Conclusions:, There is a perturbance in intercellular adhesion molecules and EGFR expression/function in oral cancer with major clinical impact. E-cad and ,-cat seem to inhibit EGFR to enhance the progression of OSCCs. [source]

Platelet-activating factor and human meningiomas

NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 6 2006
Y. Denizot
Meningiomas are common primary intracranial tumours. Platelet-activating factor (PAF) is an inflammatory and angiogenic lipid mediator involved in several types of cancer. The presence of PAF receptor (PAF-R) transcripts, the levels of PAF, the phospholipase A2 activity (PLA2, the enzymatic activity implicated in PAF formation) and the PAF acetylhydrolase activity (AHA, the PAF degrading enzyme) were investigated in 49 human meningiomas. PAF-R transcripts, PAF, PLA2 and AHA were detected in meningiomas. However, their levels did not correlate with biological parameters such as the tumour grade, the presence of associated oedema, necrosis, mitotic index as well as intensity of the neovascularization and chronic inflammatory response. In conclusion, PAF is present in meningiomas where it might act on tumour growth by altering the local angiogenic and/or cytokine networks as previously suggested for human breast and colorectal cancer. [source]

Immunohistochemical estimation of cell cycle entry and phase distribution in astrocytomas: applications in diagnostic neuropathology

NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 5 2005
Ian S. Scott
An immunohistochemical method for assessing cell cycle phase distribution in neurosurgical biopsies would enable such data to be incorporated into diagnostic algorithms for the estimation of prognosis and response to adjuvant chemotherapy in glial neoplasms, without the requirement for flow cytometric analysis. Paraffin-embedded sections of intracerebral gliomas (n = 48), consisting of diffuse astrocytoma (n = 9), anaplastic astrocytoma (n = 8) and glioblastoma (n = 31), were analysed by immunohistochemistry using markers of cell cycle entry, Mcm-2 and Ki67, and putative markers of cell cycle phase, cyclins D1 (G1-phase), cyclin A (S-phase), cyclin B1 (G2-phase) and phosphohistone H3 (Mitosis). Double labelling confocal microscopy confirmed that the phase markers were infrequently coexpressed. Cell cycle estimations by immunohistochemistry were corroborated by flow cytometric analysis. There was a significant increase in Mcm-2 (P < 0.0001), Ki67 (P < 0.0001), cyclin A (P < 0.0001) and cyclin B1 (P = 0.002) expression with increasing grade from diffuse astrocytoma through anaplastic astrocytoma to glioblastoma, suggesting that any of these four markers has potential as a marker of tumour grade. In a subset of glioblastomas (n = 16) for which accurate clinical follow-up data were available, there was a suggestion that the cyclin A:Mcm-2 labelling fraction might predict a relatively favourable response to radical radiotherapy. These provisional findings, however, require confirmation by a larger study. We conclude that it is feasible to obtain detailed cell cycle data by immunohistochemical analysis of tissue biopsies. Such information may facilitate tumour grading and may enable information of prognostic value to be obtained in the routine diagnostic laboratory. [source]

Histomorphometry of brain tumours

NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 4 2004
R. Nafe
In this review, the results of previous histomorphometric studies of brain tumours are summarized and discussed with respect to their potential value for diagnostic purposes and for tumour research. In the majority of these studies, human gliomas were investigated. In a few studies, human meningiomas and other human or experimental tumour types were investigated. A computerized image analysis system was used for the morphometric analyses in most studies. The three main histologic structures examined were tumour cell nuclei, nucleolar organizer regions and tumour vessels. The current state of knowledge provides evidence that a diagnostic benefit could be provided by histomorphometric investigations of brain tumours, especially for grading of gliomas and with respect to independent prognostic information. Additional studies are necessary to delineate the spectrum of histomorphometric parameters and the investigation of their prognostic significance for cases with the same tumour type and tumour grade. Together with many recently published observations in this field, this review shows that histomorphometry is an important approach towards the investigation of brain tumour biology. [source]

Vascular endothelial growth factor expression in oligodendrogliomas: a correlative study withSainte-Anne malignancy grade, growth fractionand patient survival

NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 4 2000
P. Varlet
Microangiogenesis is a delayed but crucial event in the malignant progression of oligodendrogliomas. Accord-ingly, in the new Sainte-Anne grading system of oligodendrogliomas, endothelial hyperplasia and contrast enhancement, both being indicators of microangiogenesis, are key criteria for the distinction of grade A from grade B tumours. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor: a strong correlation between VEGF expression, Sainte-Anne malignancy grade and patient outcome might thus be expected. In order to assess this hypothesis, VEGF immunostaining was performed in a series of 34 oligodendrogliomas that included 11 grade B and 23 grade A, of which nine became grade B during the study period (mean clinical and imaging follow-up: 41 months). VEGF expression correlated strongly with Sainte-Anne tumour grade (P < 0.001), and inversely with patient survival (P < 0.001) and recurrence-free survival (P = 0.002). One hundred per cent of grade B but only 17% of grade A were VEGF-positive. By contrast, the MIB-1 labelling index did not correlate with VEGF expression, total survival or recurrence-free survival. In accordance with the grading system, this study showed that, in oligodendrogliomas, VEGF expression and microangiogenesis are progression-related phenomena that confer on these tumours a growth advantage by presumably reducing hypoxia-induced apoptotic cell death. These findings might have important implications in the future for the indication and timing of anti-angiogenic therapies. [source]

An investigation of human brain tumour lipids by high-resolution magic angle spinning 1H MRS and histological analysis

NMR IN BIOMEDICINE, Issue 7 2008
Kirstie S. Opstad
Abstract NMR-visible lipid signals detected in vivo by 1H MRS are associated with tumour aggression and believed to arise from cytoplasmic lipid droplets. High-resolution magic angle spinning (HRMAS) 1H MRS and Nile Red staining were performed on human brain tumour biopsy specimens to investigate how NMR-visible lipid signals relate to viable cells and levels of necrosis across different grades of glioma. Presaturation spectra were acquired from 24 adult human astrocytoma biopsy samples of grades II (8), III (2) and IV (14) using HRMAS 1H MRS and quantified using LCModel to determine lipid concentrations. Each biopsy sample was then refrozen, cryostat sectioned, and stained with Nile Red, to determine the number of lipid droplets and droplet size distribution, and with Haematoxylin and Eosin, to determine cell density and percentage necrosis. A strong correlation (R,=,0.92, P,<,0.0001) was found between the number of Nile Red-stained droplets and the ,1.3,ppm lipid proton concentration by 1H MRS. Droplet sizes ranged from 1 to 10,µm in diameter, and the size distribution was constant independent of tumour grade. In the non-necrotic biopsy samples, the number of lipid droplets correlated with cell density, whereas in the necrotic samples, there were greater numbers of droplets that showed a positive correlation with percentage necrosis. The correlation between 1H MRS lipid signals and number of Nile Red-stained droplets, and the presence of lipid droplets in the non-necrotic biopsy specimens provide good evidence that the in vivo NMR-visible lipid signals are cytoplasmic in origin and that formation of lipid droplets precedes necrosis. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Discovery of myopodin methylation in bladder cancer,

THE JOURNAL OF PATHOLOGY, Issue 1 2008
V Cebrian
Abstract Myopodin is an actin-binding protein that shuttles between the nucleus and the cytoplasm. After identifying an enriched CpG island encompassing the transcription site of myopodin, we aimed at evaluating the potential relevance of myopodin methylation in bladder cancer. The epigenetic silencing of myopodin by hypermethylation was tested in bladder cancer cells (n = 12) before and after azacytidine treatment. Myopodin hypermethylation was associated with gene expression, being increased in vitro by this demethylating agent. The methylation status of myopodin promoter was then evaluated by methylation-specific polymerase chain reaction (MS-PCR) analyses. Myopodin was revealed to be frequently methylated in a large series of 466 bladder tumours (68.7%). Myopodin methylation was significantly associated with tumour stage (p < 0.0005) and tumour grade (p = 0.037). Myopodin expression patterns were analysed by immunohistochemistry on tissue arrays containing bladder tumours for which myopodin methylation was assessed (n = 177). The presence of low nuclear myopodin expression alone (p = 0.031) or combined with myopodin methylation (p = 0.008) was associated with poor survival. Moreover, myopodin methylation in 164 urinary specimens distinguished patients with bladder cancer from controls with a sensitivity of 65.0%, a specificity of 79.8%, and a global accuracy of 75.3%. Thus, myopodin was identified to be epigenetically modified in bladder cancer. The association of myopodin methylation and nuclear expression patterns with cancer progression and clinical outcome, together with its ability to detect bladder cancer patients using urinary specimens, suggests the utility of incorporating myopodin methylation assessment in the clinical management of patients affected by uroepithelial neoplasias. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

Selective over-expression of fibroblast growth factor receptors 1 and 4 in clinical prostate cancer,

THE JOURNAL OF PATHOLOGY, Issue 1 2007
K Sahadevan
Abstract Fibroblast growth factor receptors (FGFRs) mediate the tumourigenic effects of FGFs in prostate cancer. These receptors are therefore potential therapeutic targets in the development of inhibitors to this pathway. To identify the most relevant targets, we simultaneously investigated FGFR1,4 expression using a prostate cancer tissue microarray (TMA) and in laser capture microdissected (LCM) prostate epithelial cells. In malignant prostates (n = 138) we observed significant FGFR1 and FGFR4 protein over-expression in comparison with benign prostates (n = 58; p < 0.0001). FGFR1 was expressed at high levels in the majority of tumours (69% of grade 3 or less, 74% of grade 4 and 70% of grade 5), while FGFR4 was strongly expressed in 83% of grade 5 cancers but in only 25% of grade 1,3 cancers (p < 0.0001). At the transcript level we observed a similar pattern, with FGFR1 and FGFR4 mRNA over-expressed in malignant epithelial cells compared to benign cells (p < 0.0005 and p < 0.05, respectively). While total FGFR2 was increased in some cancers, there was no association between expression and tumour grade or stage. Transcript analysis, however, revealed a switch in the predominant isoform expressed from FGFR2IIIb to FGFR2IIIc among malignant epithelial cells. In contrast, protein and transcript expression of FGFR3 was very similar between benign and cancer biopsies. The functional effect of targeting FGFR4 in prostate cancer cells has not previously been investigated. In in vitro experiments, suppression of FGFR4 by RNA interference effectively blocked prostate cancer cell proliferation (p < 0.0001) and invasion (p < 0.001) in response to exogenous stimulation. This effect was evident regardless of whether the cells expressed the FGFR4 Arg388 or Gly388 allele. In parallel experiments, FGFR3 suppression had no discernible effect on cancer cell behaviour. These results suggest evidence of selective over-expression of FGFR1 and FGFR4 in clinical prostate cancer and support the notion of targeted inhibition of these receptors to disrupt FGF signalling. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

FGFR3 protein expression and its relationship to mutation status and prognostic variables in bladder cancer,

THE JOURNAL OF PATHOLOGY, Issue 1 2007
DC Tomlinson
Abstract FGFR3 is frequently activated by mutation in urothelial carcinoma (UC) and represents a potential target for therapy. In multiple myeloma, both over-expression and mutation of FGFR3 contribute to tumour development. To define the population of UC patients who may benefit from FGFR-targeted therapy, we assessed both mutation and receptor over-expression in primary UCs from a population of new patients. Manual or laser capture microdissection was used to isolate pure tumour cell populations. Where present, non-invasive and invasive components in the same section were microdissected. A screen of the region of the highest tumour stage in each sample yielded a mutation frequency of 42%. Mutations comprised 61 single and five double mutations, all in hotspot codons previously identified in UC. There was a significant association of mutation with low tumour grade and stage. Subsequently, non-invasive areas from the 43 tumours with both non-invasive and invasive components were analysed separately; 18 of these had mutation in at least one region, including nine with mutation in all regions examined, eight with mutation in only the non-invasive component and one with different mutations in different regions. Of the eight with mutation in only the non-invasive component, six were predicted to represent a single tumour and two showed morphological dissimilarity of fragments within the block, indicating the possible presence of distinct tumour clones. Immunohistochemistry showed over-expression of FGFR3 protein in many tumours compared to normal bladder and ureteric controls. Increased expression was associated with mutation (85% of mutant tumours showed high-level expression). Overall, 42% of tumours with no detectable mutation showed over-expression, including many muscle-invasive tumours. This may represent a non-mutant subset of tumours in which FGFR3 signalling contributes to the transformed phenotype and which may benefit from FGFR-targeted therapies. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

EFFECT OF RESECTION AND OUTCOME IN PATIENTS WITH RETROPERITONEAL SARCOMA

ANZ JOURNAL OF SURGERY, Issue 6 2006
Antonio Chiappa
Background: A consecutive series of 47 patients with retroperitoneal sarcoma (RPS) were resected and prospectively followed. Method: Between July 1994 and March 2005, 47 patients (24 men, 23 women; mean age, 56 years; range, 17,82 years) were evaluated. Results: A total of 23 patients had primary RPS and 24 patients had recurrent RPS. A total of 30 out of 47 patients (64%) underwent removal of contiguous intra-abdominal organs. The peroperative mortality was nil and significant preoperative complications occurred in eight cases only (17%). High tumour grade and incomplete resection were significant variables for a worse survival in all 47 patients, both in the univariate and multivariate analyses (P = 0.008 and P = 0.016, respectively). Among 28 radically resected patients, only histological grade affected overall survival (90% 5-year survival for low-grade tumour vs 26% 5-year survival for high-grade tumour; P = 0.006) with a similar effect noted for disease-free survival. Conclusions: Histological grade was the only factor that affected overall and disease-free survival for RPS tumours. An aggressive surgical approach in both primary and recurrent RPS is associated with long-term survival. [source]

Expression of CD44s and CD44v6 in transitional cell carcinomas of the urinary bladder: comparison with tumour grade, proliferative activity and p53 immunoreactivity of tumour cells,

APMIS, Issue 11 2007
JITKA KUNCOVÁ
Alterations of CD44 glycoproteins have been shown to play an important role in progression of various malignancies, including urothelial cancer. We investigated expression patterns of CD44s and CD44v6 in transitional cell carcinoma (TCC) of the urinary bladder in relation to tumour grade, proliferative activity, and immunoreactivity for p53. The selected markers were detected immunohistochemically in 122 samples of TCC. We found a close relationship between CD44s and CD44v6 expression and tumour grade. The extension of positive staining for CD44s and CD44v6 towards the luminal surface was a predominant feature of differentiated carcinomas (grades 1 and 2), suggesting deranged maturation of cancer cells related to their neoplastic transformation. Heterogeneous expression of CD44s and CD44v6 predominated in poorly differentiated tumours (G3,4). However, areas of squamous differentiation within the high-grade tumours displayed strong immunoreactivity for both CD44s and CD44v6. The proliferative activity and p53 overexpression increased with the dedifferentiation of the tumour. The results of this study are discussed in relation to the significance of CD44 expression in TCC and to the explanation for controversial results reported in previous studies on the relationship between CD44 expression and the biological behaviour of urothelial cells. [source]

Survival of patients with nonmetastatic pT3 renal tumours: a matched comparison of laparoscopic vs open radical nephrectomy

BJU INTERNATIONAL, Issue 11 2009
Karim Bensalah
OBJECTIVES To compare the oncological outcome of patients with pT3 renal tumours treated either by laparoscopic radical nephrectomy (LRN) or open RN (ORN). PATIENTS AND METHODS In a retrospective review of a multi-institutional database, we identified 1003 patients with a T3N0M0 renal tumour and with no vena caval invasion. Sixty-five patients treated by LRN were matched with up to four patients treated by ORN. Exact matches were made for age, gender, tumour size, perirenal fat invasion, renal vein invasion, and histological subtype. Following the matching process there were 44 patients treated by LRN and 135 by ORN. Qualitative and continuous variables were compared using chi-square and independent-sample t -tests, respectively. Differences in survival were compared using the Kaplan-Meier method. A Cox regression model was used to test the effect of variables on survival. RESULTS The two groups were comparable for age (P = 0.4), gender, tumour size (P = 0.4), tumour grade (P = 0.25) and histological subtype (P = 0.45). The mean follow-up was longer in the ORN group (55 vs 28 months, P < 0.001). There was no difference in survival between the ORN and LRN groups in the whole T3 population (P = 0.7), in those with perirenal fat invasion (P = 0.9), or in the subset with renal vein invasion (P = 0.31). In univariate analysis, the only predictor for death from cancer was tumour grade (P = 0.05). In multivariate analysis, no variable was significantly associated with cancer survival. CONCLUSIONS LRN has no adverse effect on cancer survival compared to ORN in patients with microscopic T3 renal cancer. Additional prospective evaluation is warranted. [source]

Adjuvant chemotherapy for bladder cancer does not alter cancer-specific survival after cystectomy in a matched case-control study

BJU INTERNATIONAL, Issue 11 2008
Jochen Walz
OBJECTIVE To assess the effect of adjuvant chemotherapy (ACHT; methotrexate, vinblastine, adriamycin and cisplatin, MVAC, or gemcitabine/cisplatin, GC) on the rate of cancer-specific survival and overall survival, as the benefit of ACHT after radical cystectomy (RC) for bladder cancer is controversial. PATIENTS AND METHODS Within a study group of 958 patients treated with RC between 1984 and 2003, we identified 274 (29.0%) with a high risk of progression due to pT3 or pT4 and/or pN1-3 stages. Of these, 129 (46.6%) received ACHT (MVAC in 103, GC in 26). These patients were then matched with the remaining patients who were unexposed to ACHT. Exact matches were made for pT stage, tumour grade, pN stage and lymphovascular invasion. Age (±5 years) and year of surgery (±5 years) were calliper-matched. Matching resulted in 62 patients treated with RC/ACHT and 65 treated with RC alone. Kaplan-Meier, life-table and Cox regression analyses were used to assess cancer-specific and overall survival. RESULTS There was no statistically significant difference in cancer-specific survival probabilities at 5 years after RC between the two groups (relative risk 1.2; P = 0.5). There was also no difference in overall survival at 5 years (1.1; P = 0.7). In multivariable analyses the delivery of adjuvant chemotherapy was not an independent predictor for survival endpoints (P = 0.3 for cancer-specific and 0.3 for overall survival). CONCLUSIONS This matched case-control analysis showed that either MVAC or GC chemotherapy had no effect on cancer-specific or overall survival after RC in high-risk patients. Further randomized long-term studies are necessary to confirm these results. [source]

Predicting outcome in minimally invasive (T1a and T1b) urothelial bladder carcinoma using a panel of biomarkers: a high throughput tissue microarray analysis

BJU INTERNATIONAL, Issue 5 2007
Paulette Mhawech-Fauceglia
OBJECTIVE To evaluate the protein expression of fibroblast growth factor receptor-3 (FGFR3), hamartin, 14-3-3,, Aurora-A, and E-cadherin using immunohistochemistry (IHC) in a series of human bladder carcinomas and to evaluate their value in distinguishing T1a from T1b tumours and in predicting their behaviour, as T1 urothelial bladder tumours present great diagnostic and therapeutic challenges to pathologists and clinicians. PATIENTS, MATERIALS AND METHODS Tissue microarrays were constructed from 94 patients (Ta 20, T1a 31, T1b 14, and T2 29 patients) using tissue obtained at first disease presentation. RESULTS FGFR3 and 14-3-3, were the only markers that were significantly associated with tumour grade and 14-3-3, was significantly associated with tumour stage. Furthermore, none of these markers could help in distinguishing T1a from T1b tumours. After adjusting for the E-cadherin expression, FGFR3 expression was a significant factor in predicting the time to recurrence in T1a/T1b. Furthermore, among all the clinical variables, grade and depth of invasion were the only ones that had a significant value in predicting T1a/T1b tumour progression. CONCLUSIONS Even though the staging of T1 to T1a/T1b is not a common practice and it is not included in the Tumour-Node-Metastasis classification, our data clearly confirmed the importance of a proper sub-staging of T1 tumours whenever feasible. [source]

A comparison of the pathology of transitional cell carcinoma of the bladder and upper urinary tract

BJU INTERNATIONAL, Issue 6 2005
Grant D. Stewart
OBJECTIVE To clarify the histopathological patterns of upper and lower urinary tract transitional cell carcinomas (TCCs), as previous reports suggest that upper urinary tract TCCs have a greater tendency towards high-grade disease than bladder TCCs, of which most are low-grade and low-stage tumours. PATIENTS AND METHODS All patients presenting with TCC of bladder or upper urinary tract between February 1991 and December 2001 at one institution were identified. Further patient information was obtained from the hospital database and case-note review. RESULTS In all, 164 patients with upper urinary tract TCC and 2197 with bladder TCC were identified. There was a correlation between grade and stage of both upper urinary tract and bladder TCCs. 35% of the upper tract TCCs were classified as grade 2 and 44% as grade 3, while for bladder TCCs, 31% of lesions were classified as grade 2 and 35% as grade 3 (P = 0.003). Of the upper urinary tract lesions 33% were stage pT2,T4, compared with only 20% of bladder TCCs (P = 0.001). CONCLUSIONS Upper urinary tract TCC is a higher grade and stage disease than bladder cancer, a finding that emphasizes the need for aggressive treatment of upper urinary tract TCC. If endourological management of upper urinary tract TCC is considered, histopathological determination of tumour grade before treatment is essential. [source]

A clinicopathological study of the expression of extracellular matrix components in urothelial carcinoma

BJU INTERNATIONAL, Issue 4 2005
Elli Ioachim
OBJECTIVE To measure the immunohistochemical expression of the extracellular matrix (ECM) components tenascin, fibronectin, collagen type IV and laminin in urothelial carcinomas, and to correlate their expression with clinicopathological features to clarify the prognostic value of these molecules and their role in tumour progression. MATERIALS AND METHODS Tumour specimens obtained during transurethral resection of bladder tumour (TURBT) from 103 patients (82 men and 2 1 women, mean age 66.7 years, range 27,89) were studied retrospectively. The expression of tenascin, fibronectin, collagen type IV and laminin was correlated with clinicopathological features (tumour grade and stage, multiplicity, simultaneous in situ component, the proliferative activity as estimated by the two proliferation associated indices, Ki-67 and proliferating cell nuclear antigen, the recurrence rate, and the progression of invading tumour). Specimens investigated for tenascin expression from patients with superficial bladder cancers were categorized into 28 treated by TURBT only and 53 who had TURBT followed by intravesical instillations of interferon. RESULTS Cytoplasmic tenascin expression was detected in tumour cells in 20% of specimens. Tenascin was expressed in the tumour stroma in 76% of specimens, and was positively correlated with tumour grade and stage. Stromal tenascin expression was positively correlated with proliferative activity, and with the expression of fibronectin and collagen type IV. Fibronectin was expressed in the tumour stroma in 89% of specimens and was positively correlated with tumour stage, proliferative activity, and expression of collagen type IV and laminin. Collagen type IV was expressed in 93% of specimens, and was positively correlated with tumour grade and stage. Laminin was expressed in 78% of specimens and had no significant correlation with the clinicopathological features. Patients treated with TURBT alone and who had low levels of tenascin had a longer tumour-free interval than those with high levels of tenascin. CONCLUSION Levels of tenascin might be valuable for predicting the risk of early recurrence. The expression of tenascin, fibronectin and collagen type IV seems to be correlated with more aggressive tumour behaviour. Furthermore, their interrelationships could indicate that they are involved in the remodelling of bladder cancer tissue, probably influencing tumour progression. [source]

Socio-economic deprivation and survival in bladder cancer

BJU INTERNATIONAL, Issue 4 2004
Gulnaz Begum
OBJECTIVES To investigate the relationship between deprivation, delay and survival from bladder cancer in the West Midlands, as socio-economic deprivation is associated with worse survival in many malignancies, and it has been suggested that treatment differences and delay in seeking care are major contributing causes. PATIENTS AND METHODS Data were prospectively collected on 1537 newly diagnosed cases of urothelial cancer presenting in the West Midlands between January 1991 and June 1992. Survival was censored at 31 July 2000, when 785 (51%) patients had died. The influence of deprivation on survival was explored using cause-specific and all-cause mortality. RESULTS Patients in less affluent groups had significantly worse survival than patients in more affluent groups when considering deaths from all causes (P = 0.02), which held true when adjusting for independent prognostic factors (age, smoking history, and tumour grade, stage, type and size). Bladder cancer-specific mortality showed no significant difference between socio-economic groups (P = 0.30). CONCLUSION Socio-economic deprivation is a significant predictor of survival when death from all causes is considered. However, this does not hold true for bladder cancer-specific death. The perceived differences in treatment and delay between socio-economic groups do not seem to occur for bladder cancer in the West Midlands. [source]

Superficial papillary urothelial carcinomas in young and elderly patients: a comparative study

BJU INTERNATIONAL, Issue 3 2004
Mario Migaldi
OBJECTIVE To compare the clinicopathological and immunohistochemical findings of superficial papillary transitional cell carcinomas in ,young' and ,elderly' patients, as the natural history and prognosis of bladder tumours in young patients remains a matter of debate. PATIENTS AND METHODS Tumours from 50 patients with superficial urothelial tumours of the bladder diagnosed before 45 years old (,young' group, follow-up 25,119 months) were compared with 90 similar tumours developed in patients aged >55 years (,elderly', follow-up 24,102 months). All the patients had a transurethral resection with curative intent, and none had received any therapy before surgery. After surgery only patients diagnosed with pT1 tumours were treated by intravesical bacille Calmette-Guérin (BCG) instillations; all received intravesical BCG if there was a recurrence. The clinicopathological variables, recurrence and disease-free interval to recurrence were assessed. Proliferative activity (MIB-1) and expression of cell-cycle regulation proteins cyclin D1, p53 and p27kip1 were detected by immunohistochemistry in the tumours of both groups. RESULTS There were statistically significant differences in tumour grade, stage and occurrence between the ,young' and ,elderly' groups. The ,young' group had a longer disease-free interval to recurrence. Among the immunohistochemical markers analysed, only MIB-1 and cyclin D1 were associated with an increased risk of recurrence in the ,young' group (P < 0.04 and <0.01, respectively) in a univariate analysis. CONCLUSIONS Superficial papillary urothelial tumours of the bladder in ,young' patients had a better prognosis than those in the ,elderly' group, showing a lower grade and stage at diagnosis, and a lower recurrence rate. Proliferative activity and cyclin D1 expression levels were of prognostic significance for the risk of recurrence in these patients. [source]

Bacillus Calmette-Guérin therapy in stage Ta/T1 bladder cancer: prognostic factors for time to recurrence and progression

BJU INTERNATIONAL, Issue 7 2004
P. Andius
OBJECTIVE To report prognostic factors for time to recurrence and progression after bacillus Calmette-Guérin (BCG) prophylaxis in patients with stage Ta/T1 papillary bladder cancer. PATIENTS AND METHODS The clinical records were assessed retrospectively for 236 patients with papillary stage Ta/T1 bladder cancer treated with BCG between 1986 and 2000. Patients with known carcinoma in situ were excluded. The median (range) follow-up was 44 (4,155) months. The effect of 13 variables on the time to recurrence and progression was evaluated using multivariate Cox proportional hazard regression and Kaplan-Meier analyses. RESULTS The recurrence rate was markedly reduced for all grades and stages. Patients with a negative first cystoscopy and maintenance BCG had a significantly longer time to recurrence than those treated with an induction course alone (P < 0.001). Thirty-seven patients (16%) progressed in stage. The result of the first cystoscopy (P < 0.001), tumour grade (P = 0.003) and six or fewer initial instillations (P = 0.002) had prognostic importance for the time to progression. Twenty-eight patients (12%) had a history of an upper tract tumour, which was 3,10 times the expected rate. Age, number of tumours, number of positive cystoscopies, length of tumour history before BCG, BCG strain and treatment year had no influence on time to recurrence and progression. CONCLUSIONS Maintenance treatment does not seem to be necessary among patients with TaG1-G2 disease after a negative first cystoscopy, as the progression rate was very low. One new finding was that BCG seemed to be equally effective among patients with or with no history of an upper tract tumour. Another new and surprising finding was that patients treated with fewer than six induction instillations, because of very bothersome side-effects, had an increased risk of tumour progression and of local failure. [source]

A preoperative clinical prognostic model for non-metastatic renal cell carcinoma

BJU INTERNATIONAL, Issue 9 2003
L. Cindolo
Authors from Naples, Paris and Rennes describe their efforts to develop a model for the preoperative prediction of outcome for non-metastatic renal cancer. It is valuable to both urologist and patient to develop such a model, particularly so on preoperative criteria. The results of their study are interesting, leading to possibly helpful findings. In another article, authors from Iceland estimated the risk of developing prostate and other cancer among relatives of men from that country diagnosed with prostate cancer. They found that a family history is a risk factor for prostate cancer, with the risk potentially higher for relatives of patients who died from the disease. From the relative dearth of papers on quality of life after radical prostatectomy there are now several, and the authors from Bristol report on the effects of erectile dysfunction on quality of life after this type of treatment. They had a very high response rate (91%) to their questionnaire, and found that erectile dysfunction has a profound effect on quality of life. This finding is not a surprise, but do we need to examine our management of prostate cancer in the light of it? OBJECTIVE To develop a model to predict the outcome before surgery for non-metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS The records of 660 patients with non-metastatic RCC, operated at three European medical institutes, were reviewed. Univariate and multivariate analyses were used to assess the clinical and pathological variables affecting disease-free survival. RESULTS The median (range) follow-up was 42 (2,180) months; the disease recurred in 110 patients (16%). The 2- and 5-year overall survival was 87% and 54%, respectively. Five variables were significant in the univariate analysis, i.e. clinical presentation, clinical and pathological size, tumour grade and stage (P < 0.05). The preoperative variables, e.g. clinical presentation and clinical tumour size, were retained from the multivariate model. A recurrence risk formula (RRF) was constructed from this model, as (1.28 × presentation (asymptomatic = 0; symptomatic = 1) + (0.13 × clinical size)). Using this equation, the 2- and 5-year disease-free survival was 96% and 93% for an RRF of ,,1.2 and 83% and 68% for an RRF of >,1.2. CONCLUSION A formula was developed which, independent of stage, can be used to predict the rate of treatment failure in patients who undergo nephrectomy for non-metastatic RCC. The RRF might be useful for more accurate sub-grouping of good-prognosis patients, and for counselling patients before surgery, their personalized follow-up or adjuvant treatment once available. [source]

Relationship between hormone receptor status and tumour size, grade and comedo necrosis in ductal carcinoma in situ,

Pathological determinants of survival in node-negative oesophageal cancer,

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 12 2004
O. A. Khan
Background: Many studies have analysed prognostic factors following oesophagectomy, but few have examined survival determinants in node-negative (N0) oesophageal cancer. The prognostic significance of a number of histological variables following surgical resection of N0 oesophageal cancer was studied. Methods: The case notes of 219 patients undergoing potentially curative oesophagectomy for N0 squamous cell carcinoma or adenocarcinoma of the oesophagus were reviewed. Details of the patient's sex, age at operation, histological type, longitudinal tumour length, tumour (T) stage, circumferential resection margin involvement, tumour grade, presence of vascular invasion, perineural invasion, Barrett's metaplasia, and survival were noted. Univariate and multivariate analyses were performed to identify prognostic factors. Results: Univariate analysis revealed three factors that correlated with poor prognosis: T stage (P = 0·024), adenocarcinoma (P = 0·033) and degree of differentiation (P = 0·001). Multivariate analysis revealed that all three were significant independent adverse prognostic indicators. Conclusion: Surgical resection of node-negative oesophageal cancer is associated with diverse long-term outcomes. This diversity of outcome is not reflected in the tumour node metastasis (TNM)-based staging system. The utility of the TNM system in predicting prognosis after surgical resection is open to question. Copyright © 2004 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source]

Elevated Ki-67 expression is correlated with TNF,- and IFN,-induced apoptosis in tumour cells

CELL PROLIFERATION, Issue 6 2002
Heinz Baisch
The expression of Ki-67 in tumour cells induced to apoptosis by tumour-necrosis-factor , (TNF,) and interferon , (IFN,) was studied. Ki-67 is known as a proliferation marker which is expressed in cycling cells, but not in resting quiescent or Go cells. In numerous studies, the proportion of tumours expressing Ki-67 was determined and related to tumour grade or prognosis. A high percentage of Ki-67 expressing cells and a low apoptotic index were regarded as an indication of a progressive tumour. This implied that Ki-67 expression and apoptosis were contrary traits. In this study, the level of Ki-67 expression in human tumour cells in culture was measured after induction of apoptosis. The Ki-67 level was determined by flow cytometry and apoptosis was measured by various methods including PARP degradation (western blot) in detached and floating cells. While the floating cells were all apoptotic, more than 80% of the attached cells showed no apoptotic signs. The Ki-67 level of apoptotic cells was elevated about 3-fold compared to viable attached control cells. However, the cytokine-treated attached cells also expressed Ki-67 at similar high levels to the apoptotic floating cells, depending on sensitivity. The plot of Ki-67 level vs. remaining cells after treatment revealed a strong correlation between the level of Ki-67 expression and the sensitivity to cytokine-induced apoptosis. This implies that proliferation pathways and apoptotic signal transduction are connected. [source]