Biomedical subjects

Lars Egevad

Publications and source records attributed to Lars Egevad.

40 records · Page 3Linked to original sources

PubMed2002

Endoglin (CD105) is expressed on immature blood vessels and is a marker for survival in prostate cancer.

BACKGROUND: Endoglin, a receptor for some of the members of the transforming growth factor-beta (TGF-beta) family, is expressed on proliferating endothelial cells and has been suggested as a marker of ongoing angiogenesis. In this study, endoglin was evaluated as a prognostic factor for prostate cancer progression. METHODS: Immunohistochemical staining of endoglin was examined in 72 cases of prostate cancer and compared with immunohistochemical staining of the pan-endothelial marker von Willebrand factor (vWf), clinicopathological factors, and cancer-specific survival. Micro-vessels were measured in the most vascularized fields. Double staining with antibodies against smooth muscle actin and endoglin or vWf, respectively, was performed in order to evaluate vessel maturation. RESULTS: Endoglin-stained tumor vessels were generally small and only 19% also stained with actin. Endoglin was a better prognostic marker than vWf. The median survival times were shorter for patients with tumor vascular count (vc) above median than for patients with vc below median (4 vs. 12 years, P = 0.0007, and 5 vs. 10 years, P = 0.018, for endoglin and vWf, respectively). Endoglin vc was associated with Gleason score (P = 0.001), local tumor stage (P = 0.0006), metastasis (P = 0.01), tumor cell immunoreactivity for TGF-beta1 (P = 0.0003), and tumor cell proliferation index (r(s) = 0.319, P = 0.02). Endoglin, in contrast to vWf, vc was prognostic for survival in the subgroup of patients with Gleason score 5, 6, and 7 tumors. CONCLUSIONS: Endoglin marks principally small, probably newly formed tumor vessels in zthe prostate, and is a promising prognostic marker for prostate cancer patients.

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PubMed2002

Interobserver reproducibility of percent Gleason grade 4/5 in total prostatectomy specimens.

PURPOSE: Recently the percent Gleason grade 4/5 was proposed as a predictor of the outcome of prostate cancer and it has been shown that it adds prognostic information to that given by Gleason score. To our knowledge the interobserver variability of percent Gleason grade 4/5 has not yet been investigated. We assessed the percent Gleason grade 4/5, including the identification of high grade patterns and estimation of the percent tumor area, which is potentially more difficult than conventional Gleason grading. MATERIALS AND METHODS: A consecutive series of 69 total prostatectomy specimens was reviewed. A single slide per specimen was circulated among 4 genitourinary pathologists, who assessed Gleason score and the percent Gleason grade 4/5. Results were compared pairwise and a weighted kappa was calculated for Gleason score and the percent Gleason grade 4/5. RESULTS: The 4 observers had a mean weighted kappa for Gleason score and the percent Gleason grade 4/5 of 0.52 to 0.66 (overall mean 0.56) and 0.58 to 0.72 (overall mean 0.66), respectively. The best agreement for percent Gleason grade 4/5 was in 2 pathologists at the same department (weighted kappa 0.86). Transition zone tumors had a lower weighted kappa for Gleason score but a higher weighted kappa for percent Gleason grade 4/5 than peripheral zone tumors. In cases of the greatest disagreement in the percent Gleason grade 4/5 crush artifact, cribriform cancer and high grade PIN within the tumor were significantly more common. An intraobserver reproducibility of weighted kappa 0.91 was achieved for Gleason score and the percent Gleason grade 4/5. CONCLUSIONS: Interobserver reproducibility of the percent Gleason grade 4/5 is substantial and at least as good as that of the Gleason score. Hence, concern about interobserver variability should not deter pathologists from using the percent Gleason grade 4/5 as a prognostic marker for prostate cancer.

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PubMed2002

Molecular epidemiology of VHL gene mutations in renal cell carcinoma patients: relation to dietary and other factors.

Carcinogenic chemicals act through DNA damage and mitogenic effects. No established mechanism explains the cancer preventive effects, if any, of food items, such as vegetables and fruit. If such data were available, preferably on tumor-initiating genes, the evidence for the protective effects would become stronger. The von Hipple-Lindau (VHL) gene is the tumor suppressor gene predisposing to both sporadic renal cell carcinoma (RCC) and von Hippel-Lindau disease. We have earlier analyzed VHL mutations in RCCs from 102 Swedish patients identified in a case-control study and here examine associations between patient characteristics, including dietary habits and mutations, considering the type of mutation. The results are given as odds ratios (OR), separately for smokers and all patients. In univariate analysis, consumption of vegetables and citrus fruit decreased the frequency of VHL mutations among smokers and citrus fruit among all patients. In multivariate analysis of smokers' characteristics, welding fumes showed a risk of 5.63 for multiple VHL mutations. In smokers, citrus fruit decreased the OR of GC to AT mutations to 0.13 and that of multiple mutations to 0.17; vegetables decreased the OR for single mutations to 0.22. Among all subjects, welding fumes were a risk factor and citrus fruit a protective factor. Additionally, an intake of selenium protected against multiple mutations. The present results provide evidence that the intake of vegetables, selenium and particularly of citrus fruit protects the renal VHL gene from mutational insults that may be endogenous or common in a population. Even though most of the associations are biologically plausible, and vegetables and fruit were an a priori hypothesis, fortuitous results cannot be ruled out in this relatively small study.

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PubMed2002

Percent Gleason grade 4/5 as prognostic factor in prostate cancer diagnosed at transurethral resection.

PURPOSE: We investigated the value of percent Gleason grade 4/5 as a predictor of long-term outcome in men with prostate cancer diagnosed at transurethral resection who received deferred treatment. MATERIALS AND METHODS: A series of 305 men with prostate cancer diagnosed at transurethral resection from 1975 to 1990 who had subsequent expectancy was analyzed. Mean patient age at diagnosis was 74 years (range 52 to 95). Slides were reviewed, and the Gleason score, percent Gleason grade 4/5 and modified Gleason score (the sum of the dominant and worst grades) were assessed. RESULTS: At followup 271 men (89%) had died, including 110 (36%) of prostate cancer. Gleason score, percent Gleason grade 4/5 and modified Gleason score were significant predictors of disease specific survival (p <0.001). Of all men 34% had tumors without any grade 4/5 pattern, of whom only 8% died of prostate cancer compared with 52% with any grade 4/5 pattern (p <0.001). Gleason score 6 tumors with focal grade 4 (less than 5%) had a worse prognosis than pure Gleason score 3 + 3 = 6 tumors (p = 0.008). There was nonsignificantly shorter survival for Gleason score 4 + 3 = 7 than for Gleason score 3 + 4 = 7 disease (p = 0.19). In Cox models including all possible pairs of Gleason score, percent Gleason grade 4/5 and modified Gleason score the percent Gleason grade 4/5 and modified Gleason score were stronger than Gleason score, although all 3 were independently significant prognosticators. CONCLUSIONS: Percent Gleason grade 4/5, modified Gleason score and Gleason score are predictors of disease specific survival in patients with prostate cancer on deferred treatment. Our study indicates that any grade 4/5 pattern impairs the prognosis significantly.

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