Biomedical subjects

J Overgaard

Publications and source records attributed to J Overgaard.

At least 19 recordsLinked to original sources

PubMed2006

Genetic analysis of the estrogen-related receptor alpha and studies of association with obesity and type 2 diabetes.

BACKGROUND: The estrogen-related receptor alpha (ERRalpha or NR3B1) is a transcription factor from the nuclear receptor super-family, group III. The gene encoding ERRalpha (ESRRA) is located on chromosome 11q13, a region showing genetic linkage to body mass index and fat percentage. Through interaction with the peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha), ERRalpha regulates key enzymes involved in the beta-oxidation of fatty acids. RESULTS: By screening 48 overweight or obese subjects for variants in the exons, exon-intron boundaries and 1000 base pairs (bp) of the promoter region of ESRRA using bi-directional nucleotide sequencing, we identified seven variants. Four rare variants had minor allele frequencies (MAF) below 1%: Pro369Pro, Gly406Asp, 3'UTR+418G>A, 3'UTR+505C>A. Two single-nucleotide polymorphisms, Pro116Pro and IVS6+65C>T (MAF 15%), were in complete linkage disequilibrium (LD) (r (2)=1). We also confirmed the presence of a reported 23 bp microsatellite repeat (ESRRA23). The Pro116Pro and ESRRA23 variants were not associated with obesity, type 2 diabetes or related phenotypes in a large population-based study of 6365 Danish whites. The two variants were examined for interactions with variants in the peroxisome proliferator-activated receptor-gamma coactivator-1alpha and -beta; however, no evidence of epistatic effects between the variants was demonstrated. CONCLUSION: The ESRRA23 and Pro116Pro variants of the gene encoding ERRalpha are not associated with obesity, type 2 diabetes or related quantitative traits in the examined Danish whites.

Aged↗

PubMed2006

Uveal and conjunctival malignant melanoma in denmark 1943-97: observed and relative survival of patients followed through 2002.

PURPOSE: To evaluate the observed and relative survival of patients diagnosed with a malignant melanoma in the ocular region in Denmark during the period 1943-97. METHODS: The study included 2,504 patients (1,292 men and 1,212 women) diagnosed with a melanoma in the ocular region, of which 2,434 cases could be topographically subclassified into 2,178 in the choroid/ciliary body, 141 in the iris, and 115 in the conjunctiva. The patients were followed through 2002 and the observed survival proportions and relative survival ratios were estimated. RESULTS: For the total ocular region and the choroid/ciliary body, the observed survival did not vary statistically significantly with the year of diagnosis. A statistically insignificant higher observed survival for women than men was found for tumors in the ocular region and the subgroups choroid/ciliary body, iris, and conjunctiva. During the 55-year study period, the 5- and 10-year relative survival remained stable for the ocular region for men at 67% and 57% and for women at 71% and 60%, respectively, and stable for the choroid/ciliary body for men at 66% and 55% and for women at 69% and 57%, respectively. The 5- and 10-year relative survival for the iris was for men 90% and 85% and for women 99% and 101%, respectively, and for the conjunctiva for men 83% and 70% and for women 93% and 82%, respectively. CONCLUSION: The observed and relative survival of patients diagnosed with a melanoma in the ocular region and choroid/ciliary body in Denmark during the period 1943-97 and followed through 2002 has remained stable. The highest observed and relative survival was found for iris melanomas, the lowest for choroid/ciliary body melanomas, and intermediate for conjunctival melanomas.

Adolescent↗

PubMed2006

Risk of radiation-induced subcutaneous fibrosis in relation to single nucleotide polymorphisms in TGFB1, SOD2, XRCC1, XRCC3, APEX and ATM--a study based on DNA from formalin fixed paraffin embedded tissue samples.

PURPOSE: In two previously published studies, associations with risk of radiation-induced subcutaneous fibrosis were found for single nucleotide polymorphisms (SNP) in TGFB1 (transforming growth factor beta 1 gene), XRCC1 (X-ray repair cross-complementing 1 gene), XRCC3 (X-ray repair cross-complementing 3 gene), SOD2 (manganese superoxide dismutase gene) and ATM (gene of ataxia telangiectasia mutated). The present study was conducted to seek a confirmation of these findings. MATERIALS AND METHODS: Like the 41 patients previously investigated, the 120 subjects included in the present study were accrued from a historical cohort of 319 post-mastectomy radiotherapy patients. All patients received hypo-fractionated radiotherapy. The TGFB1 position--509, codons 10 and 25, XRCC1 codons 194, 280 and 399, XRCC3 codon 241, SOD2 codon 16, ATM codon 1853 and APEX (apurinic/apyrimidinic exonuclease gene) codon 148 polymorphisms were assessed based on archival histological material. Differences in fibrosis risk were quantified from dose-response assessments. RESULTS: For none of the investigated polymorphisms, significant associations with risk of subcutaneous fibrosis were observed. A detailed analysis did not reveal any obvious explanation for the discrepancy between the previous and the present study. CONCLUSION: The previously observed associations with risk of radiation-induced subcutaneous fibrosis could not be replicated in the present study. Further studies are needed to elucidate the influence of genetic variation upon normal tissue radiosensitivity.

Adult↗

PubMed2006

Seasonal acquisition of chill tolerance and restructuring of membrane glycerophospholipids in an overwintering insect: triggering by low temperature, desiccation and diapause progression.

Adults of the insect Pyrrhocoris apterus acquire chill tolerance through the process of autumnal acclimatization. Field and laboratory experiments were conducted to separate the triggering effects of low temperatures, desiccation and diapause progression on the physiological characteristics related to chill tolerance with emphasis on the restructuring of glycerophospholipid (GPL) composition. Changes in relative proportions of major molecular species of glycerophosphoethanolamines (GPEtns) and glycerophosphocholines (GPChols) in thoracic muscle and fat body tissues were followed using HPLC coupled to electrospray ionisation mass spectrometry. The increase in relative proportion of 1-palmitoyl-2-linoleyl-sn-GPEtn at the expense of 1,2-dilinoleyl-sn-GPChol was the most prominent feature of the complex change observed in both tissues during autumnal acclimatization in the field. The relative proportion of total GPEtns increased, while the proportion of total GPChols decreased. The relative proportion of unsaturated fatty acyls slightly decreased. A similar restructuring response was seen during acclimatization in the field and cold acclimation in the laboratory. By contrast, the GPL changes related to desiccation and diapause progression were relatively small, differed qualitatively from the cold-acclimation response, and were accompanied with no increase of chill tolerance. Other features of autumnal acclimatization, i.e. depression of supercooling capacity and accumulation of polyhydric alcohols, were also triggered solely by low temperatures.

Acclimatization↗

PubMed2005

Studies of the association of the GNB3 825C>T polymorphism with components of the metabolic syndrome in white Danes.

AIMS/HYPOTHESIS: The 825C>T polymorphism in the gene encoding the G protein beta3 subunit (GNB3) causes enhanced G protein activation and increased in vitro cell proliferation. This polymorphism is also repeatedly associated with an increased risk of hypertension and has been studied in relation to obesity with divergent results. Only a few association studies have investigated whether this polymorphism is related to type 2 diabetes or the metabolic syndrome. We estimated the impact of the GNB3 825C>T polymorphism in relatively large-scale association studies of common phenotypes of the metabolic syndrome. MATERIALS AND METHODS: The GNB3 825C>T polymorphism was genotyped in 7,518 white Danish subjects using mass spectrometry analysis of PCR products. Case-control studies were undertaken for obesity, hypertension, type 2 diabetes and the metabolic syndrome, and a meta-analysis including data from the present study and previous studies of hypertension was performed. Quantitative trait studies of metabolic variables were carried out in 4,387 glucose-tolerant subjects. RESULTS: We observed minor differences in 825C>T genotype distributions for type 2 diabetes (CC/CT/TT 49/41/10% (control) vs 46/46/9% (cases), respectively, p=0.007); however, after correction for multiple testing, these were not statistically significant. No association was found with hypertension, obesity or the metabolic syndrome. Curiously, the T allele was associated with nominally lower systolic and diastolic blood pressure levels-a finding in contrast with most previous studies-but not with other metabolic variables. Meta-analysis demonstrated a high degree of heterogeneity between study populations of different ethnic origin. Although there was a tendency towards an increased risk of hypertension among 825T allele carriers, this was not statistically significant. CONCLUSIONS/INTERPRETATION: The present study suggests no major involvement of the GNB3 825C>T polymorphism in components of the metabolic syndrome.

Adult↗

PubMed2005

Uveal and conjunctival malignant melanoma in Denmark, 1943-97: incidence and validation study.

PURPOSE: To study the incidence of malignant melanoma in the ocular region in Denmark during the period 1943-97. METHODS: The patients were mainly identified through the Danish Cancer Registry. Age-period-cohort modelling of the incidence rates was done based on age at diagnosis, calendar period and birth cohort in 5-year groups and for each gender. RESULTS: The age-standardized incidence of malignant melanoma in the ocular region was 0.78 for men (N = 1327) and 0.65 for women (N = 1242) per 100,000 person-years. Calendar period and birth cohort had no effect on the incidence in the ocular region or in the topography subgroups choroid/ciliary body and conjunctiva. However, the incidence increased with birth cohort for iris melanomas. CONCLUSIONS: The incidence of malignant melanoma in the ocular region was stable in contrast to a major increase in cutaneous melanoma in Denmark during the period 1943-97. The incidence of iris melanomas increased substantially, whereas the rate was stable for choroid/ciliary body and conjunctival melanomas.

Adolescent↗

PubMed2004

Optimisation and validation of methods to assess single nucleotide polymorphisms (SNPs) in archival histological material.

BACKGROUND AND PURPOSE: An increasing amount of evidence indicates that single nucleotide polymorphisms (SNPs) may affect a variety of oncology related phenotypes. Occasionally, it is convenient to base studies addressing genotype-phenotype relationships on historical patient cohorts, from which only archival specimens are available. This study was conducted to validate protocols optimised for assessment of SNPs based on paraffin embedded, formalin fixed tissue samples. PATIENTS AND METHODS: In 137 breast cancer patients, three TGFB1 SNPs were assessed based on archival histological specimens. In 37 of these patients, the SNPs were also assessed using cultured fibroblasts and the assays were validated by direct comparison of the results. From the remaining 100 patients, only archival material was available. In these patients, the existence of a genetic linkage pattern between the assessed TGFB1 SNPs was used to provide an indirect validation of the genotyping results. Furthermore, two different methods for DNA extraction were compared (semi-automatic DNA extraction using the ABI Prism 6100 Nucleic Acid PrepStation versus Proteinase K digestion for 5 days followed by boiling and DNA precipitation). RESULTS: Assessment of SNPs based on archival histological material is encumbered by a number of obstacles and pitfalls. However, these can be widely overcome by careful optimisation of the methods used for sample selection, DNA extraction and PCR. Within 130 samples that fulfil the criteria for analysis a highly reliable SNP assessment was observed. The study demonstrated that different 'down-stream applications' ('single nucleotide primer extension' or 'TaqMan-based' real-time PCR) could be used as genotyping procedure. CONCLUSIONS: Reliable assessment of SNPs in formalin-fixed paraffin-embedded specimens is possible but a number of precautions should be carefully taken.

Biological Specimen Banks↗

PubMed2004

Quantitative PCR--new diagnostic tool for quantifying specific mRNA and DNA molecules: HER2/neu DNA quantification with LightCycler real-time PCR in comparison with immunohistochemistry and fluorescence in situ hybridization.

Previously, polymerase chain reaction (PCR) technology has been hampered by its inability to generate quantitative results, a drawback inherent to the high degree of amplification taking place in the reaction. Recently, PCR techniques have been described with the potential of quantifying the amount of mRNA or DNA in biological samples. In this study quantitative PCR was used to investigate the role of the EGF (epidermal growth factor) system in cancer both for measurements of mRNA concentrations and for measurements of the number of copies of specific genes. It is shown that the mRNA expression of a subset of ligands from the EGF system is increased in bladder cancer. Furthermore, measurement of the mRNA concentration gives important information such as the expression of these ligands correlated to the survival of the patients. In addition to the alterations at the mRNA level, changes also can occur at the DNA level in the EGF system. Thus, it has been demonstrated that the number of genes coding for the human epidermal growth factor receptor 2 (HER2) is increased in a number of breast tumors. It is now possible to treat breast cancer patients with a humanized antibody reacting with HER2, and the treatment is considered to be justified if the tumor displays an increased amount of HER2. For this reason there is a need for techniques suitable for HER2 measurements. A LightCycler real-time PCR method used for HER2/neu DNA quantification was evaluated and the results compared with those obtained by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Tumor biopsies were collected from 112 patients diagnosed with early breast cancer from January 1990 to March 1994. The samples were analyzed for HER2 DNA amplification by real-time PCR on LightCycler and by FISH and for HER2 protein expression by IHC. Inter-assay variation for HER2 measured by LightCycler was 10% (x =3.1; n=17). Amplification > or = 2 was observed in 19% of the patients. Concordance rates between real-time PCR and the other methods were 91% (IHC) and 92% (FISH). The correlation between real-time PCR and FISH was highly significant (p < 0.001). The "LightCycler-HER2/neu DNA quantification kit" produces results with a high level of reproducibility and its ease of use allows rapid screening for amplification of HER2. In this paper useful information is given on how real-time PCR compares with FISH and IHC. The data show that results obtained for amplification of HER2 by real-time PCR on the LightCycler instrument are comparable to results obtained by IHC and FISH.

Awards and Prizes↗

PubMed2004

Expression of integrins and E-cadherin in squamous cell carcinomas of the head and neck.

Integrins and cadherins are cell adhesion molecules suggested to play an important role in malignant progression and tumour differentiation. Our aim was to characterise the pattern of expression and the relations between integrin beta1, beta4, beta6 and E-cadherin and the different histopathological features important when judging tumour differentiation, using a well-defined scoring system. Formalin-fixed paraffin-embedded pre-irradiation biopsies from 85 patients with head and neck squamous cell carcinomas (HNSCC) were stained and evaluated for the expression of integrin beta1, beta4 and beta6 and E-cadherin. The integrins were upregulated in carcinomas compared to the adjacent mucosa and E-cadherin was downregulated. However, differences were found within the tumour: Expression of E-cadherin was lost and the three integrins were upregulated at the tumour borders, compared to central parts of the tumour biopsy. Expression of the integrins did not correlate with tumour or histopathological parameters, whereas expression of E-cadherin was correlated with high degree of keratinisation, high nuclear maturation and few mitoses - factors that characterise well-differentiated carcinomas -and E-cadherin can therefore be considered as a marker of differentiation. Furthermore, loss of adhesion expressed by low E-cadherin and integrin beta4 correlated with the presence of nodal metastases at the time of diagnosis.

Biomarkers, Tumor↗

PubMed2004

Alpha-adrenergic regulation of systemic peripheral resistance and blood flow distribution in the turtle Trachemys scripta during anoxic submergence at 5 degrees C and 21 degrees C.

Anoxic exposure in the anoxia-tolerant freshwater turtle is attended by substantial decreases in heart rate and blood flows, but systemic blood pressure (P(sys)) only decreases marginally due to an increase in systemic peripheral resistance (R(sys)). Here, we investigate the role of the alpha-adrenergic system in modulating R(sys) during anoxia at 5 degrees C and 21 degrees C in the turtle Trachemys scripta, and also describe how anoxia affects relative systemic blood flow distribution (%.Q(sys)) and absolute tissue blood flows. Turtles were instrumented with an arterial cannula for measurement of P(sys) and ultrasonic flow probes on major systemic blood vessels for determination of systemic cardiac output ((.Qsys)). Alpha-adrenergic tone was assessed from vascular injections of alpha-adrenergic agonists and antagonists (phenylephrine and phentolamine, respectively) during normoxia and following either 6 h (21 degrees C) or 12 days (5 degrees C) of anoxic submergence. Coloured microspheres, injected through a left atrial cannula during normoxia and anoxia, as well as after alpha-adrenergic stimulation and blockade during anoxia at both temperatures, were used to determine relative and absolute tissue blood flows. Anoxia was associated with an increased R(sys) and functional alpha-adrenergic vasoactivity at both acclimation temperatures. However, while anoxia at 21 degrees C was associated with a high systemic alpha-adrenergic tone, the progressive increase of R(sys) at 5 degrees C was not mediated by alpha-adrenergic control. A redistribution of blood flow away from ancillary vascular beds towards more vital circulations occurred with anoxia at both acclimation temperatures. %.Q(sys) and absolute blood flow were reduced to the digestive and urogenital tissues (approximately 2- to 15-fold), while %.Q(sys) and absolute blood flows to the heart and brain were maintained at normoxic levels. The importance of liver and muscle glycogen stores in fueling anaerobic metabolism were indicated by increases in %.Q(sys) to the muscle at 21 degrees C (1.3-fold) and liver at 5 degrees C (1.7-fold). As well, the crucial importance of the turtle shell as a buffer reserve during anoxic submergence was indicated by 40-50% of .Q(sys) being directed towards the shell during anoxia at both 5 degrees C and 21 degrees C. Alpha-adrenergic stimulation and blockade during anoxia caused few changes in %.Q(sys) and absolute tissue blood flow. However, there was evidence of alpha-adrenergic vasoactivity contributing to blood flow regulation to the liver and shell during anoxic submergence at 5 degrees C.

Adrenergic alpha-Agonists↗

PubMed2003

Independent prognostic value of angiogenesis and the level of plasminogen activator inhibitor type 1 in breast cancer patients.

Tumour angiogenesis and the levels of plasminogen activator inhibitor type 1 (PAI-1) are both informative prognostic markers in breast cancer. In cell cultures and in animal model systems, PAI-1 has a proangiogenic effect. To evaluate the interrelationship of angiogenesis and the PAI-1 level in breast cancer, we have evaluated the prognostic value of those factors in a total of 228 patients with primary, unilateral, invasive breast cancer, evaluated at a median follow-up time of 12 years. Microvessels were immunohistochemically stained by antibodies against CD34 and quantitated by the Chalkley counting technique. The levels of PAI-1 and its target proteinase uPA in tumour extracts were analysed by ELISA. The Chalkley count was not correlated with the levels of uPA or PAI-1. High values of uPA, PAI-1, and Chalkley count were all significantly correlated with a shorter recurrence-free survival and overall survival. In the multivariate analysis, the uPA level did not show independent prognostic impact for any of the analysed end points. In contrast, the risk of recurrence was independently and significantly predicted by both the PAI-1 level and the Chalkley count, with a hazard ratio (95% CI) of 1.6 (1.01-2.69) and 1.4 (1.02-1.81), respectively. For overall survival, the Chalkley count, but not PAI-1, was of significant independent prognostic value. The risk of death was 1.7 (1.30-2.15) for Chalkley counts in the upper tertile compared to the lower one. We conclude that the PAI-1 level and the Chalkley count are independent prognostic markers for recurrence-free survival in patients with primary breast cancer, suggesting that the prognostic impact of PAI-1 is not only based on its involvement in angiogenesis.

Adult↗

PubMed2003

Quantification of angiogenesis as a prognostic marker in human carcinomas: a critical evaluation of histopathological methods for estimation of vascular density.

Chalkley counts have been suggested as the primary method for immunohistochemical evaluation of angiogenesis, however, most studies have used microvessel density (MVD). We present paired Chalkley and MVD estimates in carcinomas of the prostate, breast, bladder and lung. The clinical data has previously been reported. In prostate carcinomas, high MVD indicated poor prognosis, whereas high Chalkley counts in breast carcinoma were associated with a poor prognosis. In bladder carcinoma, high estimates using both methods showed good prognosis and were associated with a high degree of inflammation. Neither of the counts revealed prognostic value in lung carcinomas, where the vascular pattern indicated that this cancer was non-angiogenic. We highlight methodological problems with both counting methods. Since angiogenic processes in lung and bladder cancers may be different from those occuring in prostate cancer, we suggest that future analyses also focus on measuring angiogenic factors to obtain more information on the biology of angiogenesis.

Biomarkers, Tumor↗

PubMed2003

The role of pelvic lymph node dissection as a predictive and prognostic factor in bladder cancer.

The aim of this study was to evaluate the value of pelvic lymph node dissection (PLND) performed as a separate procedure in a consecutive Danish bladder cancer cohort and also to analyse if the number of lymph nodes excised had an impact on outcome. From 1992 to 1998, 339 cystectomy candidates were retrospectively reviewed. Based on a preoperative PLND, 248 patients (10% N+) underwent radical cystectomy and 91 (87% N+) underwent radio- or chemotherapy. The median follow-up was 6.3 years. PLND was able to separate N+ from N0 patients with a false-negative rate of 3% compared with the following cystectomy. Lymph node-positive patients treated with cystectomy (n=24) all died from their bladder cancer. Therefore, accurate pathological N classification before the treatment decision seems worthwhile. The median number of lymph nodes excised was six and the number of lymph nodes had an independent prognostic impact on survival. This underlines the need for guidelines for surgical lymphadenectomy and the pathological assessment of lymph nodes in bladder cancer.

Adult↗

PubMed2003

Time trends and regional differences in registration, stage distribution, surgical management and survival of breast cancer in Denmark.

The aim of this study was to analyse time trends, stage at diagnosis, survival and registration of population-based cohorts of breast cancer patients in selected Danish counties (in total 2504) in 1986 and 1996-1997. In 1986, no differences in the extent of disease were observed between the counties. Patients from one county (Funen) had centralised surgery, significantly more lymph nodes removed and a better survival in the multivariate analysis. In 1996-1997, mammographical screening had been implemented in Funen, leading to a significantly better stage distribution, whereas stage remained unchanged in the other counties. In Funen, survival was significantly better than in the other counties in univariate, but not in multivariate analysis. Survival increased significantly with time only in Funen. Inclusion in clinical trials increased over time and the coverage of the database in the Danish Breast Cancer Cooperative Group (DBCG) was high. However, patients not notified in DBCG had, beside older age, also worse stage of disease distribution and less extensive surgery. A difference in survival was observed between the counties. In 1986, this may be explained by a centralised surgical system in one county, whereas in 1996-1997 improvements could be due to an early diagnosis and other as yet unknown factors. The DBCG database cannot be considered as representative of the Danish population of breast cancer patients.

Adult↗

PubMed2003

The prognostic relevance of estimates of proliferative activity in early breast cancer.

AIMS: Immunohistochemical estimates of cell proliferation evaluated with MIB-1 antibody have been suggested as prognostic indicators in different types of carcinoma. This study investigates whether MIB-1 scores add additional prognostic impact when evaluated together with classical clinicopathological parameters at diagnosis in early breast cancer patients. MATERIALS AND METHODS: Tumour specimens from 365 consecutively treated breast cancer patients were immunostained for MIB-1 and evaluated under the microscope using systematic random sampling accomplished by the CAST-grid system. RESULTS: The systematic random sampling technique resulted in MIB-1 estimates with very high interobserver and intraobserver reproducibilities (P < 0.0001). Median MIB-1 was 16% (range 0-83%). Patients were stratified by MIB-1 in tertiles, and increasing MIB-1 was significantly associated with poor overall and disease-specific survival in node-positive patients, but not in node-negative patients. High MIB-1 was significantly related to large tumour size, and strongly associated with high grade, high mitotic score, negative oestrogen receptor status and young age. In multivariate analysis, both with and without malignancy grade and number of mitoses included in the analysis, MIB-1 estimates showed no independent prognostic impact. CONCLUSIONS: High MIB-1 estimates did not add independent prognostic information at diagnosis when evaluated together with classical prognostic markers of early breast cancer.

Adult↗

PubMed2002

Intense inflammation in bladder carcinoma is associated with angiogenesis and indicates good prognosis.

The aim of this study was to investigate the prognostic influence of microvessel density using the hot spot method in 107 patients diagnosed with transitional cell carcinoma of the bladder. In each case, inflammation was found in the invasive carcinoma, therefore we classified the degree of inflammation as minimal, moderate or intense. Microvessel density was then reevaluated in each tumour in areas corresponding to these three categories. Median microvessel density irrespective of degree of inflammation was 71. Areas of minimal, moderate and intense inflammation were found in 48, 92 and 32 tumours. Microvessel density increased significantly with increasing degree of inflammation. Disease-specific survival was improved if areas of intense inflammation were present in the carcinoma (P=0.004). High microvessel density, irrespective of the degree of inflammation, was associated with a significantly better disease-specific survival (P=0.01). Multivariate analysis using death of disease as endpoint demonstrated an independent prognostic value of N-classification (N0, hazard ratio (HR)=1 vs N1, HR=2.89 (range, 1.52-5.52) vs N2, HR=3.61 (range, 1.84-7.08)), and intense inflammation, HR=0.48 (range, 0.24-0.96). Malignancy grade, T classification and microvessel density were not independent significant markers of poor outcome. In conclusion, inflammation was significantly correlated to microvessel density, and areas of intense inflammation were an independent marker of good prognosis.

Carcinoma, Transitional Cell↗

PubMed2002

Comparison of two T-classification systems for sino-nasal carcinoma.

It is often difficult to determine the actual site of origin of tumours originating in the sino-nasal region, and a uniform classification system that covers all tumours in this area is warranted. A retrospective series of 165 consecutive patients with sino-nasal carcinoma, treated and followed at the Aarhus University Hospital between 1963 and 1991, was evaluated and T-staged according to the Lederman classification. The 80 maxillary antrum carcinomas were also staged according to the UICC 1997 system. In univariate analysis, the UICC T-classification was prognostic for locoregional tumour control and disease-specific survival. However, when adjusted for covariates (gender and nodal involvement) in a multivariate analysis, the UICC classification was not a significant independent prognostic parameter. In contrast, the Lederman T-classification was prognostic both in univariate and multivariate analysis. The Lederman T-classification was more prognostic for locoregional control and disease-specific survival than the UICC TNM classification. In addition, the Lederman classification is easy to use and has a broader applicability as it covers all sites in the sino-nasal area.

Adenocarcinoma↗

PubMed2002

Prognostic indicators for malignant tumours of the parotid gland.

The best treatment of malignant parotid tumours still remains to be defined, and a better knowledge about the tumour features that predict the treatment result is needed. The histological classification of parotid tumours may present difficulties on account of their great morphological diversity. In a series of 152 patients with a malignant tumour of the parotid gland, the prognostic factors and treatment results were investigated over a 25-year period. Treatment consisted of surgery, radiation therapy or a combination (49%, 13% and 38% respectively). Crude 5-year survival was 50% with significant differences related to stage (stage I, 65%; stage II, 50%; stage III, 21%; and stage IV, 9%). With respect to histopathology, the adenoid cystic carcinomas and the acinic cell carcinomas had the best prognosis (76% and 67% 5-year crude survival and 53% and 67% 10-year crude survival respectively). There was a significant difference in crude survival between well/intermediate and poorly differentiated tumours (P = 0.007). In a Cox hazard regression analysis including 136 patients and using death from cancer as the end-point, the following parameters were independent prognostic predictors: T-classification (P = 0.002), M-classification (P < 0.0001), N-classification (N+versus N0) (P = 0.005), local invasion (P = 0.003) and histological differentiation of the tumour (P = 0.03). The TNM system is a good predictor of treatment outcome for malignant parotid tumours. The use of a combination of clinical and histological factors will assist the design of treatment strategies for parotid gland tumours.

Adolescent↗