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Cancer-specific Death (cancer-specific + death)
Selected AbstractsMorphological features of TMPRSS2,ERG gene fusion prostate cancer,THE JOURNAL OF PATHOLOGY, Issue 1 2007J-M Mosquera Abstract The TMPRSS2,ETS fusion prostate cancers comprise 50,70% of the prostate-specific antigen (PSA)-screened hospital-based prostate cancers examined to date, making it perhaps the most common genetic rearrangement in human cancer. The most common variant involves androgen-regulated TMPRSS2 and ERG, both located on chromosome 21. Emerging data from our group and others suggests that TMPRSS2,ERG fusion prostate cancer is associated with higher tumour stage and prostate cancer-specific death. The goal of this study was to determine if this common somatic alteration is associated with a morphological phenotype. We assessed 253 prostate cancer cases for TMPRSS2,ERG fusion status using an ERG break-apart FISH assay. Blinded to gene fusion status, two reviewers assessed each tumour for presence or absence of eight morphological features. Statistical analysis was performed to look for significant associations between morphological features and TMPRSS2,ERG fusion status. Five morphological features were associated with TMPRSS2,ERG fusion prostate cancer: blue-tinged mucin, cribriform growth pattern, macronucleoli, intraductal tumour spread, and signet-ring cell features, all with p -values < 0.05. Only 24% (n = 30/125) of tumours without any of these features displayed the TMPRSS2,ERG fusion. By comparison, 55% (n = 38/69) of cases with one feature (RR = 3.88), 86% (n = 38/44) of cases with two features (RR = 20.06), and 93% (n = 14/15) of cases with three or more features (RR = 44.33) were fusion positive (p < 0.001). To our knowledge, this is the first study that demonstrates a significant link between a molecular alteration in prostate cancer and distinct phenotypic features. The strength of these findings is similar to microsatellite unstable colon cancer and breast cancer involving BRCA1 and BRCA2 mutations. The biological effect of TMPRSS2,ERG overexpression may drive pathways that favour these common morphological features that pathologists observe daily. These features may also be helpful in diagnosing TMPRSS2,ERG fusion prostate cancer, which may have both prognostic and therapeutic implications. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Low expression of HER2 protein in breast cancer is biologically significantTHE JOURNAL OF PATHOLOGY, Issue 3 2006SM Tovey Abstract HER2 status is routinely tested using immunohistochemistry or FISH following the licensing of a therapeutic agent targeting HER2. However, neither of these methods provides quantitative information relating to the 70,80% of patients with levels of expression lower than the assay detection thresholds. In this study, radioimmunohistochemistry was used to detect quantitative HER2 protein expression in 178 breast cancers. Survival analysis was performed, as were correlations with known prognostic variables and with overexpression of other HER family members. It is demonstrated that the populations expressing very high and very low levels of HER2 are each associated with increased risk of cancer-specific death on survival analysis (p = 0.0043). The group with low levels of HER2 was more likely to be of higher grade, EGFR-positive and ER/HER3/HER4-negative. HER2-positive cases were frequently ER-negative/HER3-positive, whilst cases with normal HER2 expression were often ER-positive/HER4-positive. The aggressive nature of the tumour group with low HER2 expression may be explained by actions of other HER family members, particularly EGFR, but whether these or other factors have a negative regulatory effect on HER2 expression remains to be determined. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Genetic and plasma variation of insulin-like growth factor binding proteins in relation to prostate cancer incidence and survivalTHE PROSTATE, Issue 12 2009Mattias Johansson Abstract BACKGROUND Binding proteins regulate bioavailability of insulin-like growth factor-I (IGF-I) in the circulation and affect apoptosis of tumor cells in the prostate. We analyzed genetic variation within genes coding for IGF binding proteins in relation to prostate cancer incidence and survival. We also investigated if circulating IGFBP3 affects prostate cancer-specific survival. MATERIALS AND METHODS Eleven haplotype tagging SNPs and two single SNPs in the IGFBP1, IGFBP3, and IGFALS genes were genotyped within the CAncer Prostate in Sweden (CAPS) study including 2,774 cases and 1,736 controls. Plasma samples for analyses of total- and intact IGFBP3 levels were available for 1,521 cases and 909 controls. Complete follow-up of vital status was achieved by linkage to the Swedish Cause of Death Register. RESULTS We found no clear association between the genetic variants and prostate cancer incidence or survival. The rare allele of the IGFBP3 SNP rs2854744 was associated with elevated plasma levels of total IGFBP3 (Ptrend,=,9,×,10,8), but not intact IGFBP3 (Ptrend,=,0.16). Elevated levels of total- (Ptrend,=,0.03) and intact IGFBP3 (Ptrend,=,6,×,10,14) were associated with increased risk of prostate cancer specific death. Treatment and tumor characteristics accounted for the association with total IGFBP3, whereas the association with intact IGFBP3 was attenuated, but still statistically significant in adjusted analysis (Ptrend-adjusted,=,0.0004). Elevated intact IGFBP3 was also significantly associated with increased risk of prostate cancer-specific death among patients who were chemically or surgically castrated (Ptrend-adjusted,=,0.0003), and among patients who had not been treated (Ptrend-adjusted,=,0.02). CONCLUSIONS Circulating levels of intact IGFBP3 measured after diagnosis is associated with increased risk of prostate cancer-specific death. Prostate 69:1281,1291, 2009. © 2009 Wiley-Liss, Inc. [source] Large-scale genomic instability in colon adenocarcinomas and correlation with patient outcomeAPMIS, Issue 10 2009JOHAN BONDI The purpose of this study was to evaluate the association between DNA content in colon adenocarcinomas using high-resolution image cytometry and patient outcome. Tumours from 219 patients operated for colon adenocarcinoma were analysed using high-resolution image cytometry. Proteins involved in cell cycle propulsion (cyclins A, D1, D3 and E) and cell proliferation (c-Myc and non-membranous ,-catenin) have previously been reported in the same cohort and were included in this study. The results were related to disease-free survival and to cancer-specific death. Patients with aneuploid tumours showed shorter relapse-free survival than patients with euploid tumours (univariate log-rank test, p = 0.004 and multivariate Cox regression model p = 0.009, HR 0.51, 95% CI 0.31,0.84). Also the risk of death from cancer was greater in patients with aneuploid tumours (log-rank test, p = 0.006 multivariate Cox regression model p = 0.014, HR 0.47, 95% CI 0.26,0.86). When analysing patients with Dukes stages A and B, nuclear expression of ,-catenin was highly significantly associated with both shorter relapse-free survival (p < 0.005, HR 5.0, 95% CI 1.6,15.5) and cancer-specific death (p = 0.036, HR 6.9, 95% CI 1.1,42.1). DNA content in colon adenocarcinomas measured by image cytometry is an independent predictor of prognosis in our patients operated for colon adenocarcinoma. [source] Socio-economic deprivation and survival in bladder cancerBJU INTERNATIONAL, Issue 4 2004Gulnaz 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] TREATMENT FOR DUCTAL CARCINOMA IN SITU IN AN ASIAN POPULATION: OUTCOME AND PROGNOSTIC FACTORSANZ JOURNAL OF SURGERY, Issue 1-2 2008Esther W. L. Chuwa Background: Breast cancer is the most common cancer among Singapore women and ductal carcinoma in situ (DCIS) is believed to be the precursor of most invasive breast cancers. The incidence of DCIS has increased dramatically with mammographic screening, but its treatment remains controversial. Further, results of treatment for DCIS in Asians, and in particular Singapore women, are lacking. We review our institution's results treating a predominantly Chinese population with DCIS of the breast before the introduction of mammographic screening and aim to determine treatment outcomes and identify prognostic factors for disease recurrence. Methods: Between January 1994 and December 2000, 170 consecutive patients with DCIS were treated at our institution. One hundred and three (60.5%) were managed with breast conservation (17 with local wide excision alone and 86 with adjuvant irradiation following wide excision) whereas 67 (39.4%) underwent mastectomy. Of those who underwent wide local excision, 56 (54.3%) underwent re-excision for margin clearance. Overall, the axilla was surgically staged in 47 (27.6%) and no nodal involvement was found in all cases. Pathological specimens were reviewed by one of the authors. Median follow up was 86 months (range 4,151 months). Results: Sixty-two patients (36%) were asymptomatic at presentation whereas most (64%) presented with clinical symptoms; out of these more than half (54%) presented with a palpable lump. The median size of tumours was 13 mm (range 1.5,90 mm). Patients who underwent breast conservation surgery had oncologically more favourable lesions , with a significantly higher incidence of smaller and non-palpable lesions and lesions of lower nuclear grade. However, there was also a significantly higher incidence of local recurrence in this group. At the end of follow up, there were 12 patients (7.1%) who developed local recurrence and 8 patients (4.7%) developed contralateral disease. The crude incidence of all breast events (including both local failure and contralateral events) at 5 years was 5.6%. Median time to the development of any breast event (local recurrence or contralateral disease) was 60 months (range 12,120 months). The cumulative 5-year recurrence-free survival for patients who underwent breast conservation surgery was 94%. Factors influencing local recurrence rate were close or involved margins (,1 mm) and lack of adjuvant radiotherapy. There were no cancer-specific deaths during the period of follow up. Conclusion: Our results indicate that rates of cancer-specific survival were similar after mastectomy and breast conserving surgery. However, a close or involved margin (,1mm) and lack of adjuvant radiotherapy were associated with local recurrence, with margin status being the independent predictor for local recurrence. Our results reinforce that optimizing local therapy is crucial to improve local control rates in women treated with DCIS in our population. [source] | ||||||||||