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1.
Ailbhe M. McDermott Nicola Miller Deirdre Wall Lorcan M. Martyn Graham Ball Karl J. Sweeney Michael J. Kerin 《PloS one》2014,9(1)
Introduction
Breast cancer is a common disease with distinct tumor subtypes phenotypically characterized by ER and HER2/neu receptor status. MiRNAs play regulatory roles in tumor initiation and progression, and altered miRNA expression has been demonstrated in a variety of cancer states presenting the potential for exploitation as cancer biomarkers. Blood provides an excellent medium for biomarker discovery. This study investigated systemic miRNAs differentially expressed in Luminal A-like (ER+PR+HER2/neu-) breast cancer and their effectiveness as oncologic biomarkers in the clinical setting.Methods
Blood samples were prospectively collected from patients with Luminal A-like breast cancer (n = 54) and controls (n = 56). RNA was extracted, reverse transcribed and subjected to microarray analysis (n = 10 Luminal A-like; n = 10 Control). Differentially expressed miRNAs were identified by artificial neural network (ANN) data-mining algorithms. Expression of specific miRNAs was validated by RQ-PCR (n = 44 Luminal A; n = 46 Control) and potential relationships between circulating miRNA levels and clinicopathological features of breast cancer were investigated.Results
Microarray analysis identified 76 differentially expressed miRNAs. ANN revealed 10 miRNAs for further analysis (miR-19b, miR-29a, miR-93, miR-181a, miR-182, miR-223, miR-301a, miR-423-5p, miR-486-5 and miR-652). The biomarker potential of 4 miRNAs (miR-29a, miR-181a, miR-223 and miR-652) was confirmed by RQ-PCR, with significantly reduced expression in blood of women with Luminal A-like breast tumors compared to healthy controls (p = 0.001, 0.004, 0.009 and 0.004 respectively). Binary logistic regression confirmed that combination of 3 of these miRNAs (miR-29a, miR-181a and miR-652) could reliably differentiate between cancers and controls with an AUC of 0.80.Conclusion
This study provides insight into the underlying molecular portrait of Luminal A-like breast cancer subtype. From an initial 76 miRNAs, 4 were validated with altered expression in the blood of women with Luminal A-like breast cancer. The expression profiles of these 3 miRNAs, in combination with mammography, has potential to facilitate accurate subtype-specific breast tumor detection. 相似文献2.
Long-Term Prognostic Performance of Ki67 Rate in Early Stage,pT1-pT2, pN0, Invasive Breast Carcinoma
Fabien Reyal David Hajage Alexia Savignoni Jean-Guillaume Feron Marc Andrew Bollet Youlia Kirova Alain Fourquet Jean-Yves Pierga Paul Cottu Veronique Dieras Virginie Fourchotte Fatima Laki Severine Alran Bernard Asselain Anne Vincent-Salomon Brigitte Sigal-Zafrani Xavier Sastre-Garau 《PloS one》2013,8(3)
Background
Molecular signatures may become of use in clinical practice to assess the prognosis of breast cancers. However, although international consensus conferences sustain the use of these new markers in the near future, concerns remain about their degree of discordance and cost-effectiveness in different international settings. The present study aims to validate Ki67 as prognostic factor in a large cohort of early-stage (pT1–pT2, pN0) breast cancer patients.Methods
456 patients treated in 1995–1996 were identified in the Institut Curie database. Ki67 (MIB1) was retrospectively assessed by immunohistochemistry for all cases. The prognostic value of this index was compared to that of histological grade (HG), Estrogen receptor (ER) and HER2 status. Distant disease free interval, loco-regional recurrence, time-lapse from first metastatic diagnosis to death were analyzed.Results
All 456 patients were treated by lumpectomy plus axillary dissection and radiotherapy. 27 patients (5.9%) received systemic treatment. Tumors were classified as HG1 in 35%, HG2 in 42% and HG3 in 23% of cases. ER was expressed in 86% of the tumors, HER2 in 5% and 14% were triple negative. The median follow-up was 151 [5–191] months. Distant and loco-regional disease recurrences were observed in 16% and 18%, respectively. High (>20%) Ki67 rate [HR = 3 (1.8–4.8), p<10e−06] and HG3 [HR = 4.4 (2.2–8.6), p = 0.00002] were associated with an increased rate of distant relapse. In multivariate analysis, the Ki67 remained the only significant prognostic factor in the subgroups of ER positive HER2 negative [HR = 2.6 (1.5–4.6), p = 0.0006] and ER positive HER2 negative HG2 tumors [HR = 2.2 (1.01–4.8), p = 0.04].Conclusions
We validate the prognosis value of the Ki67 rate in small size node negative breast cancer. We conclude that Ki67 is a potential cost-effective decision marker for adjuvant therapy in early-stage HG2, pT1–pT2, pN0, breast cancers. 相似文献3.
Anna Kemp David B. Preen Christobel Saunders Frances Boyle Max Bulsara C. D’Arcy J. Holman Eva Malacova Elizabeth E. Roughead 《PloS one》2014,9(1)
Background
Australian clinical guidelines recommend endocrine therapy for all women with hormone-dependent early breast cancer. Guidelines specify tamoxifen as first-line therapy for pre-menopausal women, and tamoxifen or an aromatase inhibitor (AI) for post-menopausal women depending on the risk of recurrence based on tumour characteristics including size. Therapies have different side effect profiles; therefore comorbidity may also influence choice. We examined comorbidity, and the clinical and demographic characteristics of women commencing different therapies.Patients and Methods
We identified the first dispensing of tamoxifen, anastrozole or letrozole for women diagnosed with invasive breast cancer in the 45 and Up Study from 2004–2009 (N = 1266). Unit-level pharmacy and medical service claims, hospital, Cancer Registry, and self-reported data were linked to determine menopause status at diagnosis, tumour size, age, comorbidities, and change in subsidy restrictions. Chi-square tests and generalised regression models were used to compare the characteristics of women commencing different therapies.Results
Most pre-menopausal women commenced therapy with tamoxifen (91%). Anastrozole was the predominant therapy for post-menopausal women (57%), followed by tamoxifen (28%). Women with osteoporosis were less likely to commence anastrozole compared with tamoxifen (anastrozole RR = 0.7, 95% CI = 0.5–0.9). Women with arthritis were 1.6-times more likely to commence letrozole than anastrozole (95% CI = 1.1–2.1). Tamoxifen was more often initiated in women with tumours >1 cm, who were also ≥75 years. Subsidy restriction changes were associated with substantial increases in the proportion of women commencing AIs (anastrozole RR = 4.3, letrozole RR = 8.3).Conclusions
The findings indicate interplay of comorbidity and therapy choice for women with invasive breast cancer. Most post-menopausal women commenced therapy with anastrozole; however, letrozole and tamoxifen were more often initiated for women with comorbid arthritis and osteoporosis, respectively. Tamoxifen was also more common for women with tumours >1 cm and aged ≥75 years. Subsidy restrictions appear to have strongly influenced therapy choice. 相似文献4.
Iva Subhanova Lucie Muchova Martin Lenicek Hendrik J. Vreman Ondrej Luksan Kristyna Kubickova Miluse Kreidlova Tomas Zima Libor Vitek Petr Urbanek 《PloS one》2013,8(3)
Background and Aims
Hepatitis C virus (HCV) infection is associated with systemic oxidative stress. Since the heme catabolic pathway plays an important role in antioxidant protection, we attempted to assess the gene expression of key enzymes of heme catabolism, heme oxygenase 1 (HMOX1), heme oxygenase 2 (HMOX2), and biliverdin reductase A (BLVRA) in the liver and peripheral blood leukocytes (PBL) of patients chronically infected with HCV.Methods
Gene expressions (HMOX1, HMOX2, BLVRA) and HCV RNA were analyzed in PBL of HCV treatment naïve patients (n = 58) and controls (n = 55), with a subset of HCV patients having data on hepatic gene expression (n = 35). Based upon the therapeutic outcome, HCV patients were classified as either responders (n = 38) or treatment-failure patients (n = 20). Blood samples in HCV patients were collected at day 0, and week 12, 24, 36, and 48 after the initiation of standard antiviral therapy.Results
Compared to the controls, substantially increased BLVRA expression was detected in PBL (p<0.001) of therapeutically naïve HCV patients. mRNA levels of BLVRA in PBL closely correlated with those in liver tissue (r2 = 0.347,p = 0.03). A marked difference in BLVRA expression in PBL between the sustained responders and patients with treatment failure was detected at week 0 and during the follow-up (p<0.001). Multivariate analysis revealed that BLVRA basal expression in PBL was an independent predictor for sustained virological response (OR 15; 95% CI 1.05–214.2; P = 0.046). HMOX1/2 expression did not have any effect on the treatment outcome.Conclusion
Our results suggest that patients with chronic HCV infection significantly upregulate BLVRA expression in PBL. The lack of BLVRA overexpression is associated with non-responsiveness to standard antiviral therapy; whereas, HMOX1/2 does not seem to have any predictive potential. 相似文献5.
Background and Aims
Mutations reducing the function of Nav1.7 sodium channels entail diminished pain perception and olfactory acuity, suggesting a link between nociception and olfaction at ion channel level. We hypothesized that if such link exists, it should work in both directions and gain-of-function Nav1.7 mutations known to be associated with increased pain perception should also increase olfactory acuity.Methods
SCN9A variants were assessed known to enhance pain perception and found more frequently in the average population. Specifically, carriers of SCN9A variants rs41268673C>A (P610T; n = 14) or rs6746030C>T (R1150W; n = 21) were compared with non-carriers (n = 40). Olfactory function was quantified by assessing odor threshold, odor discrimination and odor identification using an established olfactory test. Nociception was assessed by measuring pain thresholds to experimental nociceptive stimuli (punctate and blunt mechanical pressure, heat and electrical stimuli).Results
The number of carried alleles of the non-mutated SCN9A haplotype rs41268673C/rs6746030C was significantly associated with the comparatively highest olfactory threshold (0 alleles: threshold at phenylethylethanol dilution step 12 of 16 (n = 1), 1 allele: 10.6±2.6 (n = 34), 2 alleles: 9.5±2.1 (n = 40)). The same SCN9A haplotype determined the pain threshold to blunt pressure stimuli (0 alleles: 21.1 N/m2, 1 allele: 29.8±10.4 N/m2, 2 alleles: 33.5±10.2 N/m2).Conclusions
The findings established a working link between nociception and olfaction via Nav1.7 in the gain-of-function direction. Hence, together with the known reduced olfaction and pain in loss-of-function mutations, a bidirectional genetic functional association between nociception and olfaction exists at Nav1.7 level. 相似文献6.
Purpose
To evaluate the usefulness of 2-[18F] fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) in the early detection of breast cancer tumor recurrences and its role in post-therapy surveillance.Methods
FDG-PET/CT was performed on patients with increased serum CA 15-3 levels and/or clinical/radiologic suspicion of recurrence. A group of asymptomatic patients who underwent FDG-PET/CT in the post-therapy surveillance of breast cancer served as the controls. The results were analyzed based on the patients'' histological data, other imaging modalities and/or clinical follow-up. Recurrence was defined as evidence of recurrent lesions within 12 months of the FDG-PET/CT scan.Results
Based on elevated serum CA15-3 levels (n = 31) and clinical/radiologic suspicion (n = 40), 71 scans were performed due to suspected recurrence, whereas 69 scans were performed for asymptomatic follow-up. The sensitivity and specificity of FDG-PET/CT were 87.5% and 87.1% in the patients with suspected recurrence and 77.8% and 91.7% in the asymptomatic patients. The positive predictive value in the patients with suspected recurrence (mainly due to elevated serum CA 15-3 levels) was higher than that in asymptomatic patients (P = 0.013). Recurrences were proven in 56.3% (40/71) of the patients with suspected recurrence and in 13% (9/69) of the asymptomatic patients (P<0.001). FDG-PET/CT resulted in changes in the planned management in 49.3% (35/71) of the patients with suspected recurrence and 10.1% (7/69) of the asymptomatic patients (P<0.001). After follow-up, 77.5% (55/71) of the patients with suspicious recurrences and 97.1% (67/69) of the asymptomatic patients were surviving at the end of the study (P<0.001).Conclusions
FDG-PET/CT was able to detect recurrence, and the results altered the intended patient management in the post-therapy surveillance of breast cancer. FDG-PET/CT should be used as a priority in patients with increased serum CA 15-3 levels, or with clinical/radiologic suspicion of recurrence, and might be useful for asymptomatic patients. 相似文献7.
Vassiliki Kotoula Mattheos Bobos Zoi Alexopoulou Christos Papadimitriou Kyriaki Papadopoulou Elpida Charalambous Eleftheria Tsolaki Grigorios Xepapadakis Irene Nicolaou Irene Papaspirou Gerasimos Aravantinos Christos Christodoulou Ioannis Efstratiou Helen Gogas George Fountzilas 《PloS one》2014,9(8)
Background
HER2 and TOP2A gene status are assessed for diagnostic and research purposes in breast cancer with fluorescence in situ hybridization (FISH). However, FISH probes do not target only the annotated gene, while chromosome 17 (chr17) is among the most unstable chromosomes in breast cancer. Here we asked whether the status of specifically targeted genes on chr17 might help in refining prognosis of early high-risk breast cancer patients.Methods
Copy numbers (CN) for 14 genes on chr17, 4 of which were within and 10 outside the core HER2 amplicon (HER2- and non-HER2-genes, respectively) were assessed with qPCR in 485 paraffin-embedded tumor tissue samples from breast cancer patients treated with adjuvant chemotherapy in the frame of two randomized phase III trials.Principal Findings
HER2-genes CN strongly correlated to each other (Spearman’s rho >0.6) and were concordant with FISH HER2 status (Kappa 0.6697 for ERBB2 CN). TOP2A CN were not concordant with TOP2A FISH status (Kappa 0.1154). CN hierarchical clustering revealed distinct patterns of gains, losses and complex alterations in HER2- and non-HER2-genes associated with IHC4 breast cancer subtypes. Upon multivariate analysis, non-HER2-gene gains independently predicted for shorter disease-free survival (DFS) and overall survival (OS) in patients with triple-negative cancer, as compared to luminal and HER2-positive tumors (interaction p = 0.007 for DFS and p = 0.011 for OS). Similarly, non-HER2-gene gains were associated with worse prognosis in patients who had undergone breast-conserving surgery as compared to modified radical mastectomy (p = 0.004 for both DFS and OS). Non-HER2-gene losses were unfavorable prognosticators in patients with 1–3 metastatic nodes, as compared to those with 4 or more nodes (p = 0.017 for DFS and p = 0.001 for OS).Conclusions
TOP2A FISH and qPCR may not identify the same pathology on chr17q. Non-HER2 chr17 CN patterns may further predict outcome in breast cancer patients with known favorable and unfavorable prognosis. 相似文献8.
Akihiko Adachi Yoshinori Higuchi Atsushi Fujikawa Toshio Machida Shigeo Sueyoshi Kenichi Harigaya Junichi Ono Naokatsu Saeki 《PloS one》2014,9(8)
Background
Chronic subdural hematoma (CSDH) is known to have a substantial recurrence rate. Artificial cerebrospinal fluid (ACF) is an effective irrigation solution in general open craniotomy and endoneurosurgery, but no evidence of its use in burr-hole surgery exists.Objective
To identify the potential of ACF irrigation to prevent CSDH recurrence. More specifically, to investigate the perioperative and intraoperative prognostic factors, and to identify controllable ones.Methods
To examine various prognostic factors, 120 consecutive patients with unilateral CSDH treated with burr-hole drainage between September 2007 and March 2013 were analyzed. Intraoperative irrigation was performed with one of two irrigation solutions: normal saline (NS; n = 60) or ACF (n = 60). All patients were followed-up for at least 6 months postoperatively. We also examined the morphological alternations of the hematoma outer membranes after incubation with different solutions.Results
Eleven patients (9.2%) had recurrence. Nine patients (15%) required additional surgery in the NS group, whereas only 2 patients (3.3%) in the ACF group required additional surgery. Among preoperative and intraoperative data, age (<80 years old, P = .044), thrombocyte (>22.0, P = .037), laterality (right, P = .03), and irrigation solution (ACF, P = .027) were related to smaller recurrence rates by log-rank tests. Only the type of irrigation solution used significantly correlated with recurrence in favor of ACF in both Cox proportional hazards (relative hazard: 0.20, 95% confidence interval (CI): 0.04–0.99; P = .049) and logistic regression models (odds ratio, 0.17, 95% CI: 0.03–0.92; P = .04) using these factors. Histological examinations of the hematoma membranes showed that the membranes incubated with NS were loose and infiltrated by inflammatory cells compared with those incubated with ACF.Conclusion
Irrigation with ACF decreased the rate of CSDH recurrence. 相似文献9.
Gilad Horowitz Moran Amit Oded Ben-Ari Ziv Gil Abraham Abergel Nevo Margalit Oren Cavel Oshri Wasserzug Dan M. Fliss 《PloS one》2013,8(12)
Objective
To compare frontal sinus cranialization to obliteration for future prevention of secondary mucocele formation following open surgery for benign lesions of the frontal sinus.Study Design
Retrospective case series.Setting
Tertiary academic medical center.Patients
Sixty-nine patients operated for benign frontal sinus pathology between 1994 and 2011.Interventions
Open excision of benign frontal sinus pathology followed by either frontal obliteration (n = 41, 59%) or frontal cranialization (n = 28, 41%).Main Outcome Measures
The prevalence of post-surgical complications and secondary mucocele formation were compiled.Results
Pathologies included osteoma (n = 34, 49%), mucocele (n = 27, 39%), fibrous dysplasia (n = 6, 9%), and encephalocele (n = 2, 3%). Complications included skin infections (n = 6), postoperative cutaneous fistula (n = 1), telecanthus (n = 4), diplopia (n = 3), nasal deformity (n = 2) and epiphora (n = 1). None of the patients suffered from postoperative CSF leak, meningitis or pneumocephalus. Six patients, all of whom had previously undergone frontal sinus obliteration, required revision surgery due to secondary mucocele formation. Statistical analysis using non-inferiority test reveal that cranialization of the frontal sinus is non-inferior to obliteration for preventing secondary mucocele formation (P<0.0001).Conclusion
Cranialization of the frontal sinus appears to be a good option for prevention of secondary mucocele development after open excision of benign frontal sinus lesions. 相似文献10.
Hongtao Li Daliu Min Hui Zhao Zhiyu Wang Weixiang Qi Shuier Zheng Lina Tang Aina He Yuanjue Sun Yang Yao Zan Shen 《PloS one》2013,8(6)
Background
The significance of ezrin immunoexpression and prognosis for osteosarcoma is still controversial. The aim was to provide a meta-analysis for ezrin immunoexpression and prognostic features of osteosarcoma patients.Methods
A detailed search was made in MEDLINE, EMBASE and the Web of Knowledge for relevant original articles published in English; methodological quality of the included studies was also assessed. Two reviewers extracted data independently. Studies were pooled and summary hazard ratios (HRs) and odds ratio (ORs) with corresponding confidence intervals (CIs) were calculated.Results
Final analysis of 318 patients from 5 eligible studies was performed. Combined HR of ezrin immunohistochemical staining suggested that positive immunoexpression had an unfavorable impact on osteosarcoma patients'' overall survival (n = 223 in 4 studies; HR = 4.79; 95% CI: 1.50–15.30; P = 0.008) but not on event-free survival (n = 202 in 3 studies; HR = 1.59; 95% CI: 0.61–4.15; P = 0. 0.342). Combined OR of ezrin immunohistochemical staining indicated that positive immunoexpression was associated with recurrence (n = 134 in 2 studies; OR = 3.79; 95% CI: 1.49–9.64; P = 0.005) but not with serum ALP level (n = 160 in 2 studies; OR = 2.16; 95% CI: 0.09–52.50; P = 0.637) and histological response to neoadjuvant chemotherapy(n = 260 in 4 studies; OR = 0.87; 95% CI: 0.37–2.03; P = 0.740).Conclusions
The results of this meta-analysis suggest that ezrin positive immunoexpression confers a higher risk of recurrence and a worse survival in osteosarcoma patients. Large prospective studies are needed to provide solid data to investigate the precise prognostic significance of ezrin. 相似文献11.
Nageswara Rao Tipirisetti Suresh Govatati Priyanka Pullari Sravanthi Malempati Murali Krishna Thupurani Shyam Perugu Praveen Guruvaiah Lakshmi Rao K Raghunadha Rao Digumarti Varadacharyulu Nallanchakravarthula Manjula Bhanoori Vishnupriya Satti 《PloS one》2014,9(1)
Background
Mitochondrial displacement loop (D-loop) is the hot spot for mitochondrial DNA (mtDNA) alterations which influence the generation of cellular reactive oxygen species (ROS). Association of D-loop alterations with breast cancer has been reported in few ethnic groups; however none of the reports were documented from Indian subcontinent.Methodology
We screened the entire mitochondrial D-loop region (1124 bp) of breast cancer patients (n = 213) and controls (n = 207) of south Indian origin by PCR-sequencing analysis. Haplotype frequencies for significant loci, the standardized disequilibrium coefficient (D′) for pair-wise linkage disequilibrium (LD) were assessed by Haploview Software.Principal Findings
We identified 7 novel mutations and 170 reported polymorphisms in the D-loop region of patients and/or controls. Polymorphisms were predominantly located in hypervariable region I (60%) than in II (30%) of D-loop region. The frequencies of 310‘C’ insertion (P = 0.018), T16189C (P = 0.0019) variants and 310‘C’ins/16189C (P = 0.00019) haplotype were significantly higher in cases than in controls. Furthermore, strong LD was observed between nucleotide position 310 and 16189 in controls (D′ = 0.49) as compared to patients (D′ = 0.14).Conclusions
Mitochondrial D-loop alterations may constitute inherent risk factors for breast cancer development. The analysis of genetic alterations in the D-loop region might help to identify patients at high risk for bad progression, thereby helping to refine therapeutic decisions in breast cancer. 相似文献12.
Mogens K. Boisen Christian Dehlendorff Dorte Linnemann Boye S. Nielsen Jim S. Larsen Kell ?sterlind Svend E. Nielsen Line S. Tarpgaard Camilla Qvortrup Per Pfeiffer Niels H. Holl?nder Nina Keldsen Torben F. Hansen Brita B. Jensen Estrid V. S. H?gdall Benny V. Jensen Julia S. Johansen 《PloS one》2014,9(10)
Purpose
We tested the hypothesis that expression of microRNAs (miRNAs) in cancer tissue can predict effectiveness of bevacizumab added to capecitabine and oxaliplatin (CAPEOX) in patients with metastatic colorectal cancer (mCRC).Experimental Design
Patients with mCRC treated with first line CAPEOX and bevacizumab (CAPEOXBEV): screening (n = 212) and validation (n = 121) cohorts, or CAPEOX alone: control cohort (n = 127), were identified retrospectively and archival primary tumor samples were collected. Expression of 754 miRNAs was analyzed in the screening cohort using polymerase chain reaction (PCR) arrays and expression levels were related to time to disease progression (TTP) and overall survival (OS). Significant miRNAs from the screening study were analyzed in all three cohorts using custom PCR arrays. In situ hybridization (ISH) was done for selected miRNAs.Results
In the screening study, 26 miRNAs were significantly correlated with outcome in multivariate analyses. Twenty-two miRNAs were selected for further study. Higher miR-664-3p expression and lower miR-455-5p expression were predictive of improved outcome in the CAPEOXBEV cohorts and showed a significant interaction with bevacizumab effectiveness. The effects were strongest for OS. Both miRNAs showed high expression in stromal cells. Higher expression of miR-196b-5p and miR-592 predicted improved outcome regardless of bevacizumab treatment, with similar effect estimates in all three cohorts.Conclusions
We have identified potentially predictive miRNAs for bevacizumab effectiveness and additional miRNAs that could be related to chemotherapy effectiveness or prognosis in patients with mCRC. Our findings need further validation in large cohorts, preferably from completed randomized trials. 相似文献13.
Purpose
Invasive micropapillary breast carcinoma (IMPC) is a rare pathological finding. Few studies have compared IMPC with invasive ductal breast carcinoma (IDC) according to matched nodal status and age. To better illustrate the difference between IMPC and IDC prognoses, we conducted this cohort study.Methods
51 mixed or pure IMPC patients and 102 pure IDC patients were matched for nodal status and age. Clinical and biological features as well as disease-free survival (DFS) were compared between groups.Results
More than one-half of IMPC consisted of mostly or exclusively IMPC component (meaning greater than 75%) and these tumors significantly correlated with a higher histologic grade (P = 0.016) and LVI positivity (P = 0.036) compared with mixed IMPC. IMPC displayed a significantly higher rate of estrogen receptor (ER) positivity and lymphovascular invasion (LVI) compared to matched IDC. Women diagnosed with IMPC had a slight, but not significant, reduced frequency for recurrence and metastasis compared to women with IDC (15.7% vs. 21.6%, P = 0.518). In the subgroup analysis, IMPC patients demonstrated significantly reduced survival (P = 0.018) compared to IDC patients in the T1N2–3 subpopulation, whereas IDC patients demonstrated significantly increased recurrence and metastasis (P = 0.024) compared to IMPC patients in the T2N2–3 subgroup. No difference was observed in patients with 3 or less positive lymph nodes (LNs).Conclusion
Although no difference in DFS was observed between IMPC and LN-matched IDC patients, IMPC patients demonstrated a significantly poorer outcome compared to IDC patients with smaller tumors and 4 or more positive LNs. The opposite results were observed in larger tumors and patients with 4 or more positive LNs. Therefore, we might advise more proactive treatment for IMPC patients with a smaller tumor size and extensive LN involvement. Furthermore, correlative IMPC studies should focus on this subset of patients to elucidate the genetic and/or biologic differences that contribute to metastatic potential. 相似文献14.
Jér?me Verine Jacqueline Lehmann-Che Hany Soliman Jean-Paul Feugeas Jean-Sébastien Vidal Pierre Mongiat-Artus Stéphanie Belhadj Josette Philippe Matthieu Lesage Evelyne Wittmer Stéphane Chanel Anne Couvelard Sophie Ferlicot Nathalie Rioux-Leclercq Jean-Michel Vignaud Anne Janin Stéphane Germain 《PloS one》2010,5(4)
Background
We have previously shown that angiopoietin-like 4 (angptl4) mRNA, a hypoxia-inducible gene, is highly expressed in clear cell renal-cell carcinoma (ccRCC), the most common subtype of RCC for which no specific marker is available. We here investigated whether angptl4 mRNA 1) could be a useful diagnostic and/or prognostic marker of ccRCC in a large and comprehensive retrospective series, 2) induction is dependent on the VHL status of tumors.Methodology/Principal Findings
Using in situ hybridization, we report that angptl4 mRNA is expressed in 100% of both sporadic (n = 102) and inherited (n = 6) primary ccRCCs, without any statistical association with nuclear grade (p = 0.39), tumor size (p = 0.09), stage grouping (p = 0.17), progression-free survival (p = 0.94), and overall survival (p = 0.80). Angptl4 mRNA was also expressed in 26 (87%) of 30 secondary ccRCCs but neither in any other secondary RCCs (n = 7). In contrast, angptl4 mRNA was neither expressed in 94% non-ccRCC renal tumors (papillary RCCs (n = 46), chromophobe RCCs (n = 28), and oncocytomas (n = 9)), nor in non-renal clear cell carcinomas (n = 39). Angptl4 expression was also examined in tumors associated (n = 23) or not associated (n = 66) with VHL disease. 40 (98%) hemangioblastomas expressed angptl4 whereas all pheochromocytomas (n = 23) and pancreatic tumors (n = 25) were angptl4-negative, whatever their VHL status.Conclusions/Significance
Angptl4 mRNA expression was highly associated with ccRCC (p = 1.5 10−49, Chi square test) allowing to define its expression as a diagnosis marker for primary ccRCC. Moreover, angptl4 mRNA allows to discriminate the renal origin of metastases of clear-cell carcinomas arising from various organs. Finally, inactivation of VHL gene is neither necessary nor sufficient for angptl4 mRNA induction. 相似文献15.
Mariana Maschietto Richard D. Williams Tasnim Chagtai Sergey D. Popov Neil J. Sebire Gordan Vujanic Elizabeth Perlman James R. Anderson Paul Grundy Jeffrey S. Dome Kathy Pritchard-Jones 《PloS one》2014,9(10)
Purpose
The presence of diffuse anaplasia in Wilms tumours (DAWT) is associated with TP53 mutations and poor outcome. As patients receive intensified treatment, we sought to identify whether TP53 mutational status confers additional prognostic information.Patients and Methods
We studied 40 patients with DAWT with anaplasia in the tissue from which DNA was extracted and analysed for TP53 mutations and 17p loss. The majority of cases were profiled by copy number (n = 32) and gene expression (n = 36) arrays. TP53 mutational status was correlated with patient event-free and overall survival, genomic copy number instability and gene expression profiling.Results
From the 40 cases, 22 (55%) had TP53 mutations (2 detected only after deep-sequencing), 20 of which also had 17p loss (91%); 18 (45%) cases had no detectable mutation but three had 17p loss. Tumours with TP53 mutations and/or 17p loss (n = 25) had an increased risk of recurrence as a first event (p = 0.03, hazard ratio (HR), 3.89; 95% confidence interval (CI), 1.26–16.0) and death (p = 0.04, HR, 4.95; 95% CI, 1.36–31.7) compared to tumours lacking TP53 abnormalities. DAWT carrying TP53 mutations showed increased copy number alterations compared to those with wild-type, suggesting a more unstable genome (p = 0.03). These tumours showed deregulation of genes associated with cell cycle and DNA repair biological processes.Conclusion
This study provides evidence that TP53 mutational analysis improves risk stratification in DAWT. This requires validation in an independent cohort before clinical use as a biomarker. 相似文献16.
Kai-Jun Zhao Yi-Bin Fang Qing-Hai Huang Yi Xu Bo Hong Qiang Li Jian-Min Liu Wen-Yuan Zhao Ben-Qiang Deng 《PloS one》2013,8(6)
Introduction
Few studies focused on predictors of unfavorable outcomes (modified Rankin Scale, 2–6) after reconstructive treatment of the ruptured intracranial spontaneous vertebral artery dissection aneurysms (ris-VADAs), which was evaluated based on 57 reconstructed lesions in this study.Methods
Results of 57 consecutive patients (M:F = 29∶28; median age, 48 years; range, 27 to 69 years) harboring 57 ris-VADAs, which were treated with coils combined with single stent(n = 32), double overlapping stents (n = 16), and triple overlapping stents (n = 9) between October 2000 to March 2011, were retrospectively reviewed and analyzed.Results
The available (n = 54) mean durations of angiographic and clinical follow-ups were 27 months (range, 12 to 78) and 62 months (range, 12 to 132), respectively. The involvement of PICA (p = 0.004), size of lesions (p = 0.000), quantity of stent (p = 0.001), and coil type (p = 0.002) affected the immediate obliteration grade, which was only risk factor for angiographic recurrences (p = 0.031). Although the post-treatment outcomes did not differ between single stent and multiple stents (p = 0.434), 5 angiographic recurrences, 1 rebleeding and 1 suspected rebleeding, all occurred in partial obliteration after single-stent-assisted coiling. Progressive thrombosis and in-stent obliteration were not detected on follow-up angiograms. Older age (odds ratio [OR] = 1.090; 95% confidence interval [CI], 1.004–1.184; p = 0.040) and unfavorable Hunt-Hess scale (OR = 4.289; 95%CI, 1.232–14.933; p = 0.022) were independent predictors of unfavorable outcomes in the reconstructed ris-VADAs.Conclusions
Immediate obliteration grade was only risk factor for angiographic recurrence after reconstructive treatment. Unfavorable Hunt-Hess grade and older age were independent predictors of unfavorable outcomes in ris-VADAs. 相似文献17.
Jasper V. Been Sizzle F. Vanterpool Jasmijn D. E. de Rooij G. Ingrid J. G. Rours René F. Kornelisse Martien C. J. M. van Dongen Christel J. A. W. van Gool Ronald R. de Krijger Peter Andriessen Luc J. I. Zimmermann Boris W. Kramer 《PloS one》2012,7(10)
Background
Histological chorioamnionitis (HC) is an intrauterine inflammatory process highly associated with preterm birth and adverse neonatal outcome. HC is often clinically silent and diagnosed postnatally by placental histology. Earlier identification could facilitate treatment individualisation to improve outcome in preterm newborns.Aim
Develop a clinical prediction rule at birth for HC and HC with fetal involvement (HCF) in preterm newborns.Methods
Clinical data and placental pathology were obtained from singleton preterm newborns (gestational age ≤32.0 weeks) born at Erasmus UMC Rotterdam from 2001 to 2003 (derivation cohort; n = 216) or Máxima MC Veldhoven from 2009 to 2010 (validation cohort; n = 206). HC and HCF prediction rules were developed with preference for high sensitivity using clinical variables available at birth.Results
HC and HCF were present in 39% and 24% in the derivation cohort and in 44% and 22% in the validation cohort, respectively. HC was predicted with 87% accuracy, yielding an area under ROC curve of 0.95 (95%CI = 0.92–0.98), a positive predictive value of 80% (95%CI = 74–84%), and a negative predictive value of 93% (95%CI = 88–96%). Corresponding figures for HCF were: accuracy 83%, area under ROC curve 0.92 (95%CI = 0.88–0.96), positive predictive value 59% (95%CI = 52–62%), and negative predictive value 97% (95%CI = 93–99%). External validation expectedly resulted in some loss of test performance, preferentially affecting positive predictive rather than negative predictive values.Conclusion
Using a clinical prediction rule composed of clinical variables available at birth, HC and HCF could be predicted with good test characteristics in preterm newborns. Further studies should evaluate the clinical value of these rules to guide early treatment individualisation. 相似文献18.
Background
The relationship between passive smoking exposure (PSE) and breast cancer risk is of major interest.Objective
To evaluate the relationship between PSE from partners and breast cancer risk stratified by hormone-receptor (HR) status in Chinese urban women population.Design
Hospital-based matched case control study.Setting
Chinese urban breast cancer patients without current or previous active smoking history in China Medical University 1st Hospital, Liaoning Province, China between Jan 2009 and Nov 2009.Patients
Each breast cancer patient was matched 1∶1 with healthy controls by gender and age (±2 years) from the same hospital.Measurements
The authors used unconditional logistic regression analyses to estimate odds ratio for women with PSE from partners and breast cancer risk.Results
312 pairs were included in the study. Women who endured PSE had significantly increased risk of breast cancer (adjusted OR: 1.46; 95% CI: 1.05–2.03; P = 0.027), comparing with unexposed women. Women who exposed to >5 cigarettes/day also had significant increased risk (adjusted OR: 1.99; 95% CI: 1.28–3.10; P = 0.002), as were women exposed to passive smoke for 16–25 years (adjusted OR: 1.87 95% CI: 1.22–2.86; P = 0.004), and those exposed to > 4 pack-years (adjusted OR: 1.71 95% CI: 1.17–2.50; P = 0.004). Similar trends were significant for estrogen receptor (ER)/progesterone receptor (PR) double positive subgroup(adjusted OR: 1.71; 2.20; 1.99; 1.92, respectively), but not for ER+/PR−, ER−/PR+, or ER−/PR− subgroups.Limitations
limitations of the hospital-based retrospective study, lack of information on entire lifetime PSE and low statistical power.Conclusions
Our findings provide further evidence that PSE from partners contributes to increased risk of breast cancer, especially for ER/PR double positive breast cancer, in Chinese urban women. 相似文献19.
Jing Li Yuan Huang Bao-Ning Zhang Jin-Hu Fan Rong Huang Pin Zhang Shu-Lian Wang Shan Zheng Bin Zhang Hong-Jian Yang Xiao-Ming Xie Zhong-Hua Tang Hui Li Jian-Jun He Evelyn Hsieh You-Lin Qiao Jia-Yuan Li 《PloS one》2014,9(1)
Background
Few studies have investigated the association between body mass index (BMI) and breast cancer with consideration to estrogen/progesterone/human epidermal growth factor type 2 receptor status (ER/PR/HER2) in the breast tissue among Chinese pre- and post-menopausal women.Methods
Four thousand two hundred and eleven breast cancer patients were selected randomly from seven geographic regions of China from 1999 to 2008. Demographic data, risk factors, pathologic features, and biological receptor status of cases were collected from the medical charts. Chi-square test, fisher exact test, rank-correlation analysis, and multivariate logistic regression model were adopted to explore whether BMI differed according to biological receptor status in pre- and post-menopausal women.Results
Three thousand two hundred and eighty one eligible cases with BMI data were included. No statistically significant differences in demographic characteristics were found between the cases with BMI data and those without. In the rank-correlation analysis, the rates of PR+ and HER2+ were positively correlated with increasing BMI among post-menopausal women (rs BMI, PR+ = 0.867, P = 0.001; rs BMI, HER2+ = 0.636, P = 0.048), but the ER+ rates did not vary by increasing BMI. Controlling for confounding factors, multivariate logistic regression models with BMI<24 kg/m2 as the reference group were performed and found that BMI≥24 kg/m2 was only positively correlated with PR+ status among post-menopausal breast cancer cases (adjusted OR = 1.420, 95% CI: 1.116–1.808, Wald = 8.116, P = 0.004).Conclusions
Post-menopausal women with high BMI (≥24 kg/m2) have a higher proportion of PR+ breast cancer. In addition to effects mediated via the estrogen metabolism pathway, high BMI might increase the risk of breast cancer by other routes, which should be examined further in future etiological mechanism studies. 相似文献20.
Qingkun Song Rong Huang Jing Li Jinhu Fan Shan Zheng Bin Zhang Hongjian Yang Zhonghua Tang Jianjun He Xiaoming Xie Hui Li Jiayuan Li Youlin Qiao 《PloS one》2013,8(8)