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1.
Marielle Perry Sarah Bertoli Clément Rocher Sandrine Hayette Sophie Ducastelle Fiorenza Barraco Hélène Labussière-Wallet Gilles Salles Christian Recher Xavier Thomas Etienne Paubelle 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(12):e545-e550
Background
Outcome of patients with mutation of the FLT3 tyrosine kinase domain (FLT3-TKD) in acute myeloid leukemia (AML) remains controversial.Patients and Methods
Herein, we present a retrospective study of 126 newly diagnosed patients with AML performed in 2 French centers.Results
FLT3-TKD mutations represented 12.7% of patients, whereas FLT3-internal tandem duplication (ITD) mutation was observed in 20.6% of AML cases and 1.6% of patients harbored both anomalies. At diagnosis, FLT3-TKD and FLT3-ITD were associated with higher peripheral leukocytes count and a higher blast count in bone marrow (P < 10-4). Mutations of the NPM1 gene were frequently associated to FLT3-TKD (68.7%) and FLT3-ITD (61.5%) mutations compared with FLT3 wild type (WT) patients (P < 10-4). Patients with both FLT3-TKD and NPM1 mutations (n = 12; 9.5%) showed a favorable outcome. Interestingly, mutations in NPM1 gene lost their favorable prognostic when not associated with FLT3-TKD both in univariate and multivariate analyses.Conclusion
Our data suggest that FLT3-TKD mutations should be routinely determined at the time of diagnosis. In association with NPM1 mutations, patients should follow the therapeutic schedule of favorable-risk patients with AML. 相似文献2.
Daisuke Hidaka Masahiro Onozawa Junichi Hashiguchi Naohiro Miyashita Kohei Kasahara Shinichi Fujisawa Eiko Hayase Kohei Okada Souichi Shiratori Hideki Goto Junichi Sugita Masao Nakagawa Daigo Hashimoto Kaoru Kahata Tomoyuki Endo Satoshi Yamamoto Yutaka Tsutsumi Yoshihito Haseyama Takanori Teshima 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(11):e469-e479
Background
The prognostic effect of Wilms tumor 1 (WT1) expression at the diagnosis of acute myelogenous leukemia (AML) has been controversial. The aim of the present study was to determine the correlations of WT1 expression at the diagnosis of AML with established prognostic alterations.Patients and Methods
We analyzed diagnostic bone marrow samples from 252 patients. WT1 expression, single nucleotide polymorphism (SNP) in the WT1 gene (rs16754), and Fms-like tyrosine kinase receptor-3 internal tandem duplication (FLT3-ITD) mutation were analyzed for all patients. The nucleophosmin 1 (NPM1) mutation and CCAAT/enhancer-binding protein-α (CEBPA) double mutation were analyzed for cytogenetically normal (CN)-AML. The KIT mutation was analyzed for core-binding factor AML.Results
Within the cytogenetically favorable prognosis group, WT1 expression in AML with inv(16) or t(15;17) was significantly greater than that in AML with t(8;21). In cases with CN-AML, FLT3-ITD and NPM1 mutations both correlated with greater expression of WT1, and the CEBPA double mutation was related to lower WT1 expression. The existence of both FLT3-ITD and NPM1 mutations showed synergistically greater expression of WT1 in CN-AML. SNP in the WT1 gene (rs16754) was significantly associated with lower expression of WT1. The WT1 levels were not prognostic factors in the total cohort or any cytogenetic group or stratified by SNP status.Conclusion
Because WT1 expression has correlated with known prognostic factors, the prognostic effect of WT1 levels could be misunderstood depending on the distribution of the collaborative mutations in each cohort. We have concluded that the prognostic significance of WT1 at the diagnosis of AML is weak compared with the other established prognostic factors. 相似文献3.
Fei Xu Rong Han Jian Zhang Zheng Li Jun Wang Xiao-Ling Chu Jing-Qiu Yu Chao Wang Tao Tao Hong-Jie Shen Su-Ning Chen De-Pei Wu Song-Bai Liu Qiao-Cheng Qiu Sheng-Li Xue 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(2):e107-e115
Background
FLT3 mutations have been well-studied in acute myeloid leukemia (AML), and the detection of the FLT3 gene has become a clinical routine. However, it has not been fully analyzed in other hematologic malignancies, such as myelodysplastic syndromes (MDS).Materials and Methods
Between 2010 and 2016, 304 adult patients with de novo MDS had the FLT3 sequence tested on their bone marrow sample. With 279 patients who had follow-up information, we also analyzed the impact of clinical and laboratory characteristics as well as FLT3 mutation status and treatment on prognosis.Results
We found that the transformation rate was 3 (42.9%) of 7 patients in the FLT3-ITD-positive group, compared with 31 (10.4%) of 297 among FLT3-ITD-negative patients (P = .033). The median progression-free survival of the FLT3-ITD mutated and wild-type groups were 43 days and 363.5 days, respectively (P < .0001). The median overall survival (OS) of the 2 groups were 218 days and 410.5 days, respectively (P < .0001). We also found that 5 factors had independent prognostic impact on OS: white blood cell counts, bone marrow blast percentage, cytogenetics, transplantation status, and FLT3-ITD mutation. Furthermore, compared with the transformation group, the non-progression group was younger (P = .034), with a lower platelet count (P = .022), a lower bone marrow blast percentage (P = .001), a lower FLT3-ITD incidence (P = .007), and a longer OS (P < .0001).Conclusions
When observed at the MDS stage, patients harboring FLT3-ITD mutations had higher AML transformation rate, quicker disease progression, and shorter survival than wild-type patients. Nevertheless, once the disease progressed to leukemia, the impact of FLT3-ITD mutations on prognosis was slight. In addition, the prognosis of secondary AML was very poor whether there was an FLT3-ITD mutation or not. 相似文献4.
Bolanle Gbadamosi Daniel Ezekwudo Sanjog Bastola Ishmael Jaiyesimi 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(7):e287-e294
Background
Acute myeloid leukemia (AML) is a heterogeneous malignancy with diverse genetic abnormalities, clinical presentations, and outcomes. Known predictive and prognostic factors in AML include age, performance status, comorbidities, cytogenetics, and molecular mutations. Identifying prognostic and predictive factors can inform the choice of induction therapy and outcomes prediction.Patients and Methods
A retrospective review was performed of 137 adult AML patients from 2010 to 2015. Predictors of complete remission (CR) and overall survival (OS) were determined for patients treated with 3+7 (3 days of anthracycline and 7 days of cytarabine) or hypomethylating agent. Variables associated with CR or OS were assessed using univariate Cox regression and a multivariate Cox model.Results
The average age was 65 years and 91 patients (66%), sample size is 137 patients had primary AML. Patients in the 3+7 induction group were younger, had a higher bone marrow blast percentage, and more de novo AML compared with those in the hypomethylating agent group (P < .001, P < .001, P = .005, respectively). Univariate logistic regression for CR showed a significant association between age (P < .001), choice of induction (P < .001), and monosomy (P = .015), although only induction with 3+7 (P < .001) and absence of monosomy (P = .042) remained significant in multivariate analysis. Univariate Cox regression indicated that age (P = .003), AML status (de novo or secondary; P = .0277), choice of induction (P = .030), and monosomy (P = .010) had a significant association with OS. Only younger age (P = .018) and absence of monosomy (P = .022) were predictive of OS in multivariate Cox analysis.Conclusion
Positive predictors of CR in adult AML include absence of monosomy and induction treatment with 3+7; whereas positive predictors of OS are younger age and absence of monosomy. 相似文献5.
Jianai Sun Jingjing Zhu De Zhou Lixia Zhu Xiudi Yang Mixue Xie Li Li Xianbo Huang Mingyu Zhu Yanlong Zheng Wanzhuo Xie Xiujin Ye 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(1):e63-e70
Purpose
To perform a retrospective analysis of the prognostic relevance of clinicopathologic parameters in a well-documented cohort of patients treated with all-trans-retinoic acid (ATRA)-based induction regimens in order to discover which indicators can predict a high risk of early death (ED) and patient survival.Patients and Methods
We analyzed data of 288 newly diagnosed adult acute promyelocytic leukemia patients in Hangzhou, China. The median follow-up time was 32 months (range, 6-78 months).Results
The 3-year disease-free and overall survival rates were 90.83% and 91.69%, respectively. In the multivariable analysis, older age (≥ 60 years) was the only independent risk factor for ED (hazard ratio [HR] = 15.057; P = .004). High white blood cell count was not a risk factor for ED (P = .055), but it was for relapse (HR = 2.7; P = .009). FLT3 mutation (HR = 3.9; 95% confidence interval, 1.4 to 10; P = .007) and older age (≥ 60 years) (HR = 5.3; 95% confidence interval, 2.4 to 11; P < .001) were prognostic factors for poorer disease-free and overall survival. Interestingly, CD15 negativity (HR = 0.23; P = .049) was a prognostic factor for relapse. The ED rate was 5.9% (17/288 patients).Conclusion
The perceived impact of the identification of these high-risk factors should be described in order to decide whether any modifications to treatment strategy should be entertained. 相似文献6.
Qingxiu Dang Hong Zhou Juan Qian Li Yang Jianfei Huang Yaping Zhang Wenyu Shi 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(11):749-754
Introduction
Lysosomal-associated membrane protein 1 (LAMP1) is a lysosomal and plasma membrane protein that contributes to tumor metastatic potential and differentiation.Patients and Methods
We performed immunohistochemical staining to investigate LAMP1 protein expression levels in 122 diffuse large B-cell lymphoma (DLBCL) tumor samples and 45 reactive hyperplasia tissues. Correlations between LAMP1 expression, various clinicopathologic features, and patient prognosis were evaluated by univariate and multivariate analyses.Results
LAMP1 expression was greater in the DLBCL tissues than in the reactive hyperplasia tissues. High LAMP1 expression was significantly associated with a high international prognostic index (score, 3-5; P = .023) and elevated lactate dehydrogenase level (P = .028). Moreover, high LAMP1 expression (P = .026), elevated serum lactate dehydrogenase level (P = .011), and high international prognostic index (P < .001) were independently associated with worse overall survival and progression-free survival.Conclusion
These data provide the first evidence that LAMP1 expression is associated with a poor prognosis in patients with DLBCL. 相似文献7.
Takayuki Nakayama Kazutaka Saito Jiro Kumagai Yutaka Nakajima Toshiki Kijima Soichiro Yoshida Kazunori Kihara Yasuhisa Fujii 《Clinical genitourinary cancer》2018,16(6):e1151-e1158
Introduction
C-reactive protein (CRP), a representative inflammatory marker, could serve as a biomarker in renal cell carcinoma because CRP is an important prognostic factor. However, its detailed mechanism remains unknown. This study showed that higher CRP levels correlated with the tumor immune microenvironment, which leads to a worse prognosis. These findings can help to clarify the underlying mechanisms between the presence of systemic inflammatory reaction and prognosis. The aim of this study is to investigate the association between tumor immune microenvironment and CRP in patients with renal cell carcinoma (RCC) to explore the underlying mechanisms between CRP level and prognosis.Patients and Methods
Immunohistochemical measurement of CD4, CD8, CD163 (M2 macrophages), and Foxp3 (Regulatory T [Treg] cells) was performed in patients with clear-cell RCC (n = 111) treated with radical or partial nephrectomy at our institution. The association between immunohistochemical status and preoperative serum CRP level and cancer-specific survival (CSS) was analyzed.Results
Thirty-three patients (30%) had a high CRP level (≥ 5.0 mg/L), and the CSS rate was significantly worse among these patients than among the remaining patients (P < .001). In patients with strong infiltration of CD8+, Foxp3+, or CD163+ cells, CRP levels were significantly higher (P = .041, P = .001, and P = .035, respectively), and CSS was significantly worse compared with patients with weak infiltration (P = .040, P = .026, and P < .001, respectively). In multivariate analysis, strong CD163+ cells infiltration (P = .001) as well as pathologic T3 (P = .036), lymph-node involvement (P = .007), distant metastasis (P < .001), and Fuhrman nuclear grade 4 (P = .003) were independent prognostic factors for CSS.Conclusions
Infiltration of the immunosuppressive cells known as Tregs and M2 macrophages in the tumor microenvironment is associated with higher CRP and poor prognosis in patients with clear-cell RCC. CRP could reflect an immunosuppressive microenvironment. 相似文献8.
José Carlos Jaime-Pérez José Ramón Padilla-Medina Lucía Teresa Fernández José Luis Herrera-Garza César Homero Gutiérrez-Aguirre Luz Tarín-Arzaga David Gómez-Almaguer 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(4):286-292
Introduction
The outcomes for adolescents and young adults (AYAs) with acute myeloid leukemia (AML) have been poorly characterized in Hispanics in low- to middle-income countries. The results are influenced by biologic and socioeconomic factors. The clinical paths for AYA patients with AML are reported.Patients and Methods
A retrospective analysis of AYA and pediatric AML patients aged 1 to 39 years during 2003 to 2016 from a single reference center in Northeast Mexico treated with a 7+3 standard protocol was performed. The 5-year overall survival (OS) and event-free survival (EFS) were estimated using Kaplan-Meier analysis. The hazard ratios for relapse and death were estimated using a Cox regression model. The patients with promyelocytic leukemia were analyzed separately.Results
The study included 110 non-PML AML patients, 39 children and 71 AYAs. No difference in complete remission was found (P = .446), although the overall response rate was greater in the children (87.2% vs. 69% in AYAs; P = .034). The 5-year EFS rate was 33% for the children versus 9.3% in the AYAs at a median follow-up of 22 and 9 months, respectively (P = .008). The 5-year OS rate was 51% in the children and 22% in the AYAs (P = .001). Of the 44 AYAs with complete remission, 29 (65%) developed a relapse. Of the 39 children and 71 AYAs, 20 children (51.3%) and 21 AYAs (29.6%) underwent transplantation (P = .024). Patients with refractory disease had a 1-year OS rate of 14.4%. Older age (hazard ratio [HR], 2.55; P = .002) and white blood cell count > 50 × 109/L (HR, 1.79; P = .023) were significant for death, and transplantation was protective (HR, 0.57; P = .023).Conclusion
Low EFS and OS rates were found for AML patients in the AYA group. To improve survival rates, intensified chemotherapy regimens and early hematopoietic stem cell transplantation are needed. 相似文献9.
Fatemeh Ardeshir-Larijani Priyanka Bhateja Mary Beth Lipka Neelesh Sharma Pingfu Fu Afshin Dowlati 《Clinical lung cancer》2018,19(4):e489-e501
Background
Mixed-lineage leukemia protein 2 (MLL2 or KMT2D) is a histone methyltransferase whose mutation has been associated with a poor prognosis in cancer. We compared the characteristics and significance of KMT2D alterations in non–small-cell lung cancer (NSCLC) with those in small cell lung cancer (SCLC).Patients and Methods
Tumors from 194 NSCLC patients with locally advanced or advanced disease and 64 SCLC patients underwent targeted-exome sequencing. The association of KMT2D mutation with overall survival (OS) and progression-free survival (PFS) was measured using Kaplan-Meier methods and further evaluated using multivariable Cox proportional hazards regression model adjusting for known clinical prognostic features.Results
The KMT2D mutation rate was 17.5% (34 of 194) in NSCLC. Patients with mutant KMT2D had significantly lower median OS (9.97 vs. 30.2 months; P < .0001) and median PFS (8.46 vs. 24.1 months; P = .0004) compared with patients with wild-type KMT2D. The KMT2D mutation was significantly more common in females (P = .017). Using a multivariate Cox regression model, KMT2D mutation was one of the most significant prognostic factors in NSCLC: hazard ratio (HR) for OS, 2.79 (95% confidence interval [CI], 1.8-4.33; P < .0001) and HR for PFS, 1.99 (95% CI, 1.32-3.01; P = .001). In contrast, the KMT2D mutation rate in SCLC was 32.8% (21 of 64) and showed no sex bias (P = .874). No significant change was found in survival in association with the KMT2D mutation in SCLC (OS, P = .952; PFS, P = .744).Conclusion
The KMT2D mutation was associated with reduced survival in NSCLC but not in SCLC. 相似文献10.
Bojan Zaric Luka Brcic Anna Buder Anita Brandstetter Jorun O. Buresch Stefan Traint Tomi Kovacevic Vladimir Stojsic Branislav Perin Robert Pirker Martin Filipits 《Clinical lung cancer》2018,19(6):e957-e963
Background
We assessed the prognostic value of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in patients with completely resected lung adenocarcinoma.Patients and Methods
PD-1 and PD-L1 expression was determined using immunohistochemistry in formalin-fixed paraffin-embedded surgical specimens and correlated with the clinicopathologic features and survival of 161 patients with lung adenocarcinoma.Results
PD-1 expression on immune cells was observed in 71 of 159 evaluable tumor samples (45%) and was not significantly associated with the clinicopathologic features. Multivariate analyses identified PD-1 expression as an independent prognostic factor for recurrence (adjusted hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.36-0.95; P = .03) and death (adjusted HR, 0.48; 95% CI, 0.27-0.86; P = 0.01). PD-L1 expression on tumor cells was seen in 59 of 161 cases (37%) and correlated with KRAS mutation status (P = .02) and type of surgery (P = .01). PD-L1 expression was not associated with recurrence-free survival in the patients (adjusted HR, 0.90; 95% CI, 0.55-1.48; P = .68) but correlated with longer overall survival (adjusted HR, 0.54; 95% CI, 0.30-0.97; P = .04).Conclusion
PD-1 and PD-L1 expression was associated with favorable overall survival in patients with completely resected adenocarcinoma of the lung. 相似文献11.
Bo Qiu Ying Liang QiWen Li GuiHong Liu Fang Wang ZhaoLin Chen MengZhong Liu Ming Zhao Hui Liu 《Clinical lung cancer》2017,18(6):e369-e373
Introduction
The effect of local therapy (LT) for oligoprogressive epidermal growth factor receptor (EGFR)-mutated non–small-cell lung cancer (NSCLC) has not been well established. Forty-six patients with stage IIIB/IV EGFR-mutated NSCLC were treated by LT and continuing tyrosine kinase inhibitors (TKIs) for oligoprogression. The median overall survival (OS) and progression-free survival (PFS) after LT were 13.0 and 7.0 months, respectively. EGFR mutation type, sites of LT, and time from first progressive disease (PD) to LT were prognostic of OS after LT.Purpose
Patients with advanced stage EGFR-mutated NSCLC treated with EGFR TKIs could experience oligoprogression. This study investigated the benefits of LT and continuation of TKIs for oligoprogression retrospectively.Materials and Methods
Forty-six patients with stage IIIB/IV EGFR-mutated NSCLC on TKIs were treated by LT and continuation of TKIs for oligoprogressive disease. The impact of clinicopathologic variables on survival was explored using Cox regression.Results
With a median follow-up of 32 months, the 2-year OS was 65.2%, and the estimated OS was 35.0 months. The median OS after LT (LT-OS) was 13.0 months. The median PFS after LT (LT-PFS) was 7.0 months. Univariate analysis showed that stage at initial diagnosis, EGFR mutation type, site of LT, metastatic status at initial TKIs, and time from first PD to LT correlated with LT-OS significantly. Multivariate analysis suggested that EGFR mutation type (P = .001), sites of LT (P = .000), and time from first PD to LT (P = .034) were prognostic of LT-OS. Univariate analysis showed that metastatic status at initial TKIs and time from first PD to LT correlated with LT-PFS significantly. Multivariate analysis suggested that only time from first PD to LT (P = .000) was prognostic of LT-PFS.Conclusion
This study revealed that LTs are feasible and effective for EGFR-mutated NSCLC with oligoprogression. EGFR mutation type, sites of LT, and time from first PD to LT were prognostic factors for LT-OS. Time from first PD to LT was a prognostic factor for LT-PFS. 相似文献12.
Takayoshi Tachibana Taiki Andou Masatsugu Tanaka Satomi Ito Takuya Miyazaki Yoshimi Ishii Eriko Ogusa Hideyuki Koharazawa Hiroyuki Takahashi Kenji Motohashi Jun Aoki Yuki Nakajima Kenji Matsumoto Maki Hagihara Chizuko Hashimoto Jun Taguchi Katsumichi Fujimaki Hiroyuki Fujita Hideaki Nakajima 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(6):415-421
Purpose
A multicenter retrospective analysis was performed to evaluate the clinical significance of serum ferritin at diagnosis in patients with acute myeloid leukemia (AML).Methods
The study cohort included 305 patients who were newly diagnosed with AML from 2000 to 2015 and received standard induction chemotherapy. Transplantation was performed in 168 patients.Results
The median ferritin value was 512 ng/mL (range, 8-9475 ng/mL). Ferritin correlated with lactate dehydrogenase, C-reactive protein, white blood cell count, and blast count, and elevation of ferritin was associated with poor performance status. The median follow-up period was 58 months (range, 4-187 months) among survivors. The high ferritin group (≥ 400 ng/mL) demonstrated inferior event-free survival (EFS) at the 5-year interval (30% vs. 40%; P = .033) compared to the low ferritin group. Multivariate analysis in the high-risk karyotype revealed that high ferritin levels predicted worse EFS (hazard ratio = 2.07; 95% confidence interval, 1.28-3.33; P = .003).Conclusion
Elevated ferritin at diagnosis may indicate tumor burden in patients with AML and predict worse EFS in the high-risk group. 相似文献13.
Raja Pramanik Anudishi Tyagi Anita Chopra Akash Kumar Sreenivas Vishnubhatla Sameer Bakhshi 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(6):e249-e254
Background
The purpose of our study was to evaluate the clinical, cytogenetic, and molecular features, and survival outcomes in patients with acute myeloid leukemia (AML) with myeloid sarcoma (MS) and compare them with patients with AML without MS.Patients and Methods
This was a retrospective analysis of de novo pediatric AML patients with or without MS diagnosed at our cancer center between June 2003 and June 2016.Results
MS was present in 121 of 570 (21.2%), the most frequent site being the orbit. Patients with MS had a younger median age (6 years vs. 10 years) and presented with higher hemoglobin and platelet but lower white blood cell count compared with patients without MS. Further, t (8; 21) (P < .01), loss of Y chromosome (P < .01), and deletion 9q (P = .03) were significantly higher in patients with AML with MS. Event-free survival (EFS; P = .003) and overall survival (OS; P = .001) were better among patients with AML with MS (median EFS 21.0 months and median OS 37.1 months) compared with those with AML without MS (median EFS 11.2 months and median OS 16.2 months). The t (8; 21) was significantly associated with MS (odds ratio, 3.92). In a comparison of the 4 groups divided according to the presence or absence of MS and t (8; 21), the subgroup of patients having MS without concomitant t (8; 21) was the only group to have a significantly better OS (hazard ratio, 0.53; 95% confidence interval, 0.34-0.82; P = .005).Conclusion
Although t (8; 21) was more frequently associated with MS, it did not appear to be the reason for better outcome. 相似文献14.
Mohammad Abufaraj Andrea Haitel Marco Moschini Kilian Gust Beat Foerster Mehmet ?zsoy David D&#x;Andrea Pierre I. Karakiewicz Morgan Rouprêt Alberto Briganti Shahrokh F. Shariat 《Clinical genitourinary cancer》2018,16(1):e73-e78
Background
We assessed the role of N-cadherin as a prognostic biomarker in patients with invasive bladder cancer (BCa) who had undergone radical cystectomy (RC).Patients and Methods
The present retrospective single-center study included 433 BCa patients who had undergone RC and bilateral lymph node dissection. Formalin-fixed paraffin tissue microarrays were stained with an anti–N-cadherin monoclonal mouse antibody. N-cadherin expression was considered positive if any immunoreactivity was detected. Multivariable Cox regression models were created to evaluate the prognostic effect of N-cadherin on survival.Results
N-cadherin expression was observed in 189 patients (43.7%). It was associated with advanced pathologic stage (P = .001) and lymph node metastasis (P < .001). During a median follow-up period of 10.6 years, N-cadherin expression was associated with worse recurrence-free survival, overall survival, and cancer-specific survival (P < .001, P = .001, and P < .001, respectively). On multivariable analysis adjusted for the effects of standard clinicopathologic features, N-cadherin expression retained its association with worse recurrence-free survival (hazard ratio, 1.41; 95% confidence interval, 1.02-1.92; P = .032) but not cancer-specific survival (P = .07) and overall survival (P = .3).Conclusion
N-cadherin was expressed in approximately 40% of patients with invasive BCa. Its expression was associated with features of biologically and pathologically adverse disease and worse recurrence-free survival. N-cadherin could be a part of a marker panel to help clinical decision-making and therapy for BCa. 相似文献15.
Takashi Mizuno Jordan M. Cloyd Diego Vicente Kiyohiko Omichi Yun Shin Chun Scott E. Kopetz Dipen Maru Claudius Conrad Ching-Wei D. Tzeng Steven H. Wei Thomas A. Aloia Jean-Nicolas Vauthey 《European journal of surgical oncology》2018,44(5):684-692
Introduction
Dorsophilia protein, mothers against decapentaplegic homolog 4 (SMAD4) is a key mediator in the transforming growth factor (TGF)-β signaling pathway and SMAD4 gene mutations are thought to play a critical role in colorectal cancer (CRC) progression. However, little is known about its influence on survival in patients undergoing resection for colorectal liver metastases (CLM).Methods
Between 2005 and 2015, all patients with known SMAD4 mutation status who underwent resection of CLM were identified. Patients with SMAD4 mutation were compared to those with SMAD4 wild type. Next, the prognostic value of SMAD4 mutation was validated in a separate cohort of patients with synchronous stage IV CRC who underwent systemic therapy alone.Results
Of 278 patients, 37 (13%) were SMAD4 mutant while 241 (87%) were wild type. Overall survival (OS) after hepatic resection was worse in SMAD4-mutant patients compared to SMAD4 wild type (OS rate at 3 years, 62% vs. 82%; P < 0.0001). Independent predictors for worse OS were poor differentiation (hazard ratio [HR] 2.586; P = 0.007), multiple tumors (HR 1.970; P = 0.01), diameter greater than 3 cm (HR 1.752; P = 0.017), R1 margin status (HR 2.452; P = 0.014), RAS mutation (HR 2.044; P = 0.002), and SMAD4 mutation (HR 2.773; P < 0.0001). Among 237 patients in the validation cohort, SMAD4-mutations were significantly associated with worse 3-year OS rate (22% vs. 38%; P = 0.012) and was an independent predictor for worse OS (HR, 1.647; P = 0.032).Conclusion
SMAD4 mutation is independently associated with worse outcomes among patients undergoing resection of CLM. 相似文献16.
17.
Judith Stift Alexandra Graf Christoph Schwarz Dietmar Tamandl Patrick Starlinger Merima Herac Andrea Beer Friedrich Wrba Martin Bodingbauer Klaus Kaczirek Stefan Stremitzer 《European journal of surgical oncology》2018,44(1):139-147
Background
The value of microscopic biliary and perineural invasion as prognostic biomarkers in patients with resectable colorectal liver metastases (CLM) who undergo neoadjuvant chemotherapy and liver resection is still unclear. This retrospective study was performed to elucidate this issue.Methods
Histologic slides of resected CLM of patients who underwent neoadjuvant bevacizumab-based chemotherapy and liver resection were investigated with respect to biliary and perineural invasion. Presence of invasion was correlated with radiologic and histologic response, recurrence-free survival (RFS) and overall survival (OS).Results
One hundred forty-one patients were enrolled. There was a significant association between biliary and perineural invasion, respectively (P = 0.001). Moreover, both biliary and perineural invasion were associated with bilobar metastatic spread and higher number of metastases, while perineural invasion was also associated with a higher Fong score. No significant association was found with response. In univariable analysis, biliary and perineural invasion were associated with shorter RFS (median 10.1 vs. 13.5 months, HR 2.09, P = 0.010 and 7.6 vs. 14.0, HR 2.23, P = 0.001, respectively). Biliary invasion was also associated with shorter OS (median 32.8 months vs. not reached, HR 2.78, P = 0.010), however these results did not remain significant in multivariable analysis.Conclusions
In patients with resectable colorectal liver metastases undergoing neoadjuvant bevacizumab-based chemotherapy and liver resection, biliary and perineural invasion are associated with higher tumor load but may not be prognostic biomarkers. 相似文献18.
Patrick J. McIntire Lina Irshaid Yifang Liu Zhengming Chen Faith Menken Eugene Nowak Sandra J. Shin Paula S. Ginter 《Clinical breast cancer》2018,18(6):451-458.e1
Background
CD8+ tumor-infiltrating lymphocytes (TILs) have emerged as a prognostic indicator in triple-negative breast cancer (TNBC). There is debate surrounding the prognostic value of hot spots for CD8+ TIL enumeration.Methods
We compared hot spot versus whole-tumor CD8+ TIL enumeration in prognosticating TNBC using immunohistochemistry on whole tissue sections and quantification by digital image analysis (Halo imaging analysis software; Indica Labs, Corrales, NM). A wide range of clinically relevant hot spot sizes was evaluated.Results
CD8+ TIL enumeration was independently statistically significant for all hot spot sizes and whole-tumor annotations for disease-free survival by multivariate analysis. A 10× objective (2.2 mm diameter) hot spot was found to correlate significantly with overall survival (P = .04), while the remaining hot spots and whole-tumor CD8+ TIL enumeration did not (P > .05). Statistical significance was not demonstrated when comparing between hot spots and whole-tumor annotations, as the groups had overlapping confidence intervals.Conclusion
CD8+ TIL hot spot enumeration is equivalent to whole-tumor enumeration for prognostication in TNBC and may serve as a good alternative methodology in future studies and clinical practice. 相似文献19.
Aleš Obr Vít Procházka Andrea Jirkuvová Helena Urbánková Eva Kriegova Petra Schneiderová Michaela Vatolíková Tomáš Papajík 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(11):762-768
Background
TP53 mutation (TP53mut) and a complex karyotype (CK) were shown to be predictors of poor outcome in mantle-cell lymphoma (MCL). In this study we examined the combined effect of both of these risk factors.Patients and Methods
Patients diagnosed with MCL between January 2000 and December 2014 (n = 74) were evaluated. Forty-eight of them had available material for TP53 and cytogenetic examination. We analyzed the prognostic effect of combined TP53mut and CK in the cohort of patients treated with rituximab-containing therapy.Results
Three-year (3-y) overall survival (OS) and 3-y progression-free survival (PFS) in CK patients were shorter compared with non-CK (P = .001 for OS; P = .02 for PFS). TP53mut was a predictor of shorter survival compared with TP53 wild type (OS and PFS; P < .001). The incidence of TP53mut was not significantly associated with CK (P = .240). CK and TP53mut were predictors of inferior PFS and OS independent of age and Mantle-Cell Lymphoma International Prognostic Index, with hazard ratios of 2.35 (P = .024), 4.50 (P < .001) for PFS and 4.31 (P < .001), 5.46 (P < .001) for OS analysis in the CK and TP53mut groups, respectively. The combination of TP53mut and CK status stratified the patients into 3 prognostic groups (P < .001) with the worst outcome in patients with CK and TP53mut.Conclusion
TP53 mutation and CK occurred independently and patients harboring both had a dismal prognosis. The study suggests the importance of molecular cytogenetics and examination of the TP53mut status to be performed simultaneously before treatment. 相似文献20.
C. Yang H. Cheng G. Luo Y. Lu M. Guo K. Jin Z. Wang X. Yu C. Liu 《European journal of surgical oncology》2017,43(11):2112-2118