Lymphovascular Invasion Status Research Articles

Tumor compactness improves the preoperative volumetry-based prediction of the pathological complete response of rectal cancer after preoperative concurrent chemoradiotherapy.

In addition to clinical factors (tumor and node stage) and treatment factors (equivalent radiotherapy dose and chemotherapy regimen), we assessed whether different performances of various tumor volume measurements help predict the pathological complete response (pCR) of locally advanced rectal cancer (LARC) after preoperative concurrent chemoradiotherapy (CCRT). A total of 122 patients with LARC treated with a long course of CCRT, between December 2009 and March 2015, were enrolled in this bi-institutional study. Tumor delineation was based on standard T2-weighted magnetic resonance imaging or contrast-enhanced computed tomography before CCRT. Tumor compactness was defined as the ratio of the volume and the surface area. The tumor compactness-corrected TV (TCTV) was defined as the ratio of the real TV (RTV) and tumor compactness. Twenty-three (18.9%) patients had a pCR. Areas under the curve of the receiver operating characteristic for pCR prediction calculated using the RTV, cylindrical approximated TV (CATV), and TCTV were 0.724, 0.747, and 0.780, respectively. The prediction performance of TCTV was significantly more efficient than that of both RTV (P = 0.0057) and CATV (P = 0.0329). Multivariate logistic regression analysis revealed tumor compactness (P = 0.001), RTV (P = 0.042), and preoperative clinical nodal status (P = 0.044) as significant predictors of a pCR. In addition, poor tumor compactness was closely associated with lymphovascular space invasion (P = 0.008) and pathological nodal status (P = 0.003). For patients with LARC receiving preoperative CCRT, tumor compactness is a useful radiomic parameter for improving the volumetric based prediction model.

Estimating the OncotypeDX score: validation of an inexpensive estimation tool.

OncotypeDX, a multi-gene expression assay, has been incorporated into clinical practice as a prognostic and predictive tool. However, its use in resource-constrained international healthcare systems is limited. Here we develop and validate a simplified model using clinicopathologic criteria to predict OncotypeDX score. Patients with estrogen receptor (ER) and/or progesterone receptor (PR)-positive and HER2-negative invasive ductal carcinoma for whom the OncotypeDX test was successfully performed between 09/2008 and 12/2011 were retrospectively identified. Tumor size, nuclear and histologic grade, lymphovascular invasion, and ER and PR status were extracted from pathology reports. Data were split into a training dataset comprising women tested 09/2008-04/2011, and a validation dataset comprising women tested 04/2011-12/2011. Using the training dataset, linear regression analysis was used to identify factors associated with OncotypeDX score, and to create a simplified risk score and identify risk cutoffs. Estrogen and progesterone receptors, tumor size, nuclear and histologic grades, and lymphovascular involvement were independently associated with OncotypeDX. The full model explained 39% of the variation in the test data, and the simplified risk score and cutoffs assigned 57% of patients in the test data to the correct risk category (OncotypeDX score<18, 18-30, >30). 41% of patients were predicted to have OncotypeDX score<18, of these 83, 16, and 2% had true scores of<18, 18-30, and>30, respectively. Awaiting an inexpensive test that is prognostic and predictive, our simplified tool allows clinicians to identify a fairly large group of patients (41%) with very low chance of having high-risk disease (2%).

Multifocal Invasive Ductal Cancer: Distinguishing Independent Tumor Foci From Multiple Satellites.

Patients with multifocal breast cancers (MBCs) have a poorer prognosis than patients with unifocal breast cancers. Studies have attributed this to tumor size underestimation in MBC. An alternative hypothesis is that some MBCs behave in a fashion analogous to the "satellite" and "in-transit metastasis" observed in melanoma and, thereby, are more clinically aggressive. We identified 79 cases of MBC, which we classified into 2 groups: study cases defined as ≥2 morphologically similar tumor foci with ≥1 focus without in situ carcinoma (n = 21); and a control group defined as ≥2 morphologically similar or dissimilar foci with associated in situ carcinoma in all foci (n = 58). The odds of being a study case is 1.86 (95% confidence interval [CI] 1.26-2.74) times greater per unit increase in number of tumor foci (median of 4 tumor foci; P = .002). Study cases were 73.33 (95% CI = 8.91-603.16) times more likely to have lymphovascular invasion (LVI) and 14.72 (95% CI = 4.37-49.61) times more likely to have nodal metastases. Grade I/II tumors were 0.20 (95% CI = 0.07-0.59) times less likely to be study cases. There was a significant positive interaction ( P < 0.001) indicated by the relationship of LVI status and nodal status with the study case and control group. We conclude that there is a subset of MBC that presents with more numerous tumor foci and a higher rate of nodal metastasis. The aggressive behavior of these cases may be attributed to their proclivity for LVI.

Minimum apparent diffusion coefficient for predicting lymphovascular invasion in invasive cervical cancer.

To investigate the diagnostic performance of minimum apparent diffusion coefficient (mini-ADC) for predicting lymphovascular invasion (LVI) in invasive cervical cancer. Ninety-six patients with pathologically confirmed invasive cervical cancer (CC) underwent conventional preoperative magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) on a 3.0T MRI system. Tumor ADC, mini-ADC and mini-ADC ratio (mini-ADC value / tumor ADC value) were obtained and compared between LVI-positive and LVI-negative invasive CC, and correlation between LVI status and Ki-67, p16, p63, and clinical prognostic factors were analyzed. ADC thresholds and diagnostic performance were determined by receiver operating characteristic (ROC) analysis. Tumor ADC showed no significant difference (P = 0.300) between LVI-positive invasive CC (n = 27) and LVI-negative invasive CC (n = 69); the mini-ADC and mini-ADC ratio were significantly lower in LVI-positive invasive CC than in LVI-negative invasive CC ([0.712 ± 0.078 × 10-3 mm2 /s] vs. [0.867 ± 0.099 × 10-3 mm2 /s], P < 0.001; and [0.772 ± 0.062] vs. [0.917 ± 0.052], P < 0.001, respectively). ROC curve analysis yielded a cutoff mini-ADC value of 0.837 in the differentiation of LVI-positive and LVI-negative invasive CC, with a sensitivity of 65%, specificity of 100%, and area under the curve (AUC) of 0.885; a cutoff mini-ADC ratio of 0.875 with a sensitivity of 78%, specificity of 100%, AUC of 0.970, positive predictive value of 100%, and negative predictive value of 64%. There was a positive correlation between LVI status and Ki-67 (r = 0.241, P = 0.014) and a negative correlation between mini-ADC and LVI status (r = -0.582, P < 0.001); mini-ADC and Ki-67 (r = -0.587, P < 0.001). Mini-ADC value appears to be a simple and effective tool for the prediction of LVI status in invasive CC, and the mini-ADC ratio may be the best parameter in discriminating between LVI-positive and LVI-negative invasive CC. 1 Technical Efficacy: Stage 4 J. MAGN. RESON. IMAGING 2017;45:1771-1779.

Predicting poor prognosis recurrence in women with endometrial cancer: a nomogram developed by the FRANCOGYN study group.

Background:The purpose of this study was to develop a nomogram to predict ‘poor prognosis recurrence' (PPR) in women treated for endometrial cancer (EC).Methods:The data of 861 women who received primary surgical treatment between January 2001 and December 2013 were abstracted from a prospective multicenter database. Data were randomly split into two sets: training and validation with a predefined 2/3 ratio. A Cox proportional hazards multivariate model of selected prognostic features was performed in the training cohort (n=574) to develop a nomogram predicting PPRs. The nomogram was validated in the validation cohort of 287 patients.Results:In the training cohort, 82 (14.3%) developed subsequent PPR. Age, histologic type and grade, lymphovascular space invasion status, FIGO stage, and nodal staging (SLN±pelvic and/or para-aortic lymphadenectomy) were independently associated with subsequent PPR. The nomogram showed an area under the receiver operating characteristic curve (AUC) of 0.82 (95% confidence interval (CI), 0.73–0.89) in the training set. The validation set showed a good discrimination with an AUC of 0.75 (95% CI, 0.65–0.83).Conclusions:We have developed a robust tool that is able to predict subsequent PPRs in women with FIGO I–III EC.

Diagnostic Performance of Fused Diffusion-Weighted Imaging Using T1-Weighted Imaging for Axillary Nodal Staging in Patients With Early Breast Cancer

PurposeTo evaluate the diagnostic performance of fused diffusion-weighted imaging (DWI) using T1-weighted imaging (T1WI) for axillary nodal staging in patients with early breast cancer (stage I or II). Materials and MethodsWe enrolled 149 axillae in 147 consecutive patients who performed preoperative breast magnetic resonance imaging (MRI) and definitive surgery. All patients underwent T2-weighted imaging (T2WI), fused DWI using T1WI, and non–fat-suppressed (non-FS) T1WI. Two radiologists scored each axillary nodal status by using a 5-point scale and independently measured the apparent diffusion coefficient (ADC) values of the most suspicious lymph node and an index tumor. Diagnostic performance was calculated on a patient-by-patient basis. ResultsMacrometastasis was present in 26.2%, micrometastasis in 7.4%, and benign lymph nodes in 66.4%. Area under the receiver operating characteristic curves (AUCs) of both readers for predicting axillary lymph node metastasis were 0.676 and 0.603 for non-FS T1WI, 0.749 and 0.727 for T2WI, 0.838 and 0.790 for fused DWI, and 0.868 and 0.837 for the combined reading using ADC. AUCs of tumor ADC were 0.709 and 0.737, whereas those of lymph node ADC were 0.818 and 0.781 for both readers. With stepwise addition of tumor ADC, lymph node ADC, and lymphovascular invasion status to the fused DWI, the AUCs gradually increased from 0.838, 0.892, and 0.908 to 0.924 for reader 1 and from 0.790, 0.863, and 0.901 to 0.908 for reader 2. ConclusionFused DWI using T1WI showed better diagnostic performance than conventional T2WI and non-FS T1WI for the prediction of lymph node metastasis.

Postoperative radiation therapy is associated with a reduced risk of local recurrence among low risk Merkel cell carcinomas of the head and neck

PurposeMerkel cell carcinoma (MCC) is a rare and often aggressive skin cancer. Typically, surgery is the primary treatment. Postoperative radiation therapy (PORT) is often recommended to improve local control. It is unclear whether PORT is indicated in patients with favorable Stage IA head and neck (HN) MCC. Methods and materialsWe conducted a retrospective analysis of 46 low-risk HN MCC cases treated between 2006 and 2015. Inclusion criteria were defined as a primary tumor size of ≤ 2 cm, negative pathological margins, negative sentinel lymph node biopsy, and no immunosuppression. Local recurrence (LR) was defined as tumor recurrence within 2 cm of the primary surgical bed and estimated with the Kaplan-Meier method. ResultsOmission of PORT was offered to all 46 patients, of which 23 patients received PORT and 23 did not. No patient received adjuvant chemotherapy. There were no significant differences in surgical margins, tumor size, depth, lympho-vascular invasion status, or demographics between the two patient groups. Median follow-up for all patients was 3.7 years. Six of the 23 patients who did not receive PORT developed an LR. Compared to the group that received PORT, there was a significantly higher risk of LR in the group treated without PORT (26% vs. 0%, P = .02). Median time to LR was 11 months. All local failures were effectively salvaged. There was no difference in MCC-specific and overall survival between the 2 groups. ConclusionsFor patients with HN MCC, omission of PORT was associated with a significantly higher risk of local recurrence even among those patients with the lowest-risk tumors (i.e., Stage IA without immune suppression). Thus, it is important to weigh the benefits of PORT against the side effect profile on a case-specific basis for each patient.

Histopathologic Features of Prognostic Significance in High-Grade Osteosarcoma.

Context .- In osteosarcoma treated with neoadjuvant chemotherapy the extent of tumor necrosis on resection is considered an indicator of treatment response, and this has been shown to correlate with survival in most but not all studies. Objective .- To identify additional histologic variables of prognostic significance in high-grade osteosarcoma. Design .- Slides of pretreatment biopsy and primary postneoadjuvant chemotherapy resections from 165 patients with high-grade osteosarcoma were reviewed. Univariate (Kaplan-Meier) and multivariate (Cox regression) analyses were performed to identify clinical and histomorphologic attributes associated with overall survival. Results .- Univariate analyses confirmed the prognostic significance of metastatic status on presentation, primary tumor size, anatomic site, and histologic subtype. Additionally, the identification of lymphovascular invasion, 10% or more residual viable tumor, and 10 or more mitoses per 10 high-powered fields assessed in posttreatment resections were associated with poor survival, retaining significance in multivariate analyses. Based on results from multivariate analysis, we developed a prognostic index incorporating primary tumor size and site, and significant histologic features assessed on resection (ie, lymphovascular invasion status, mitotic rate, and extent of viable tumor). This scoring system segregates patients into 3 risk categories with significant differences in overall survival and retained significance in an independent validation set of 42 cases. Conclusions .- The integration of clinical and microscopic features improves prognostication of patients with osteosarcoma.

The recurrence with isolated intra-abdominal lymph node in patients with colorectal cancer: A study of the Turkish Descriptive Oncological Researches Group (intra-abdominal lymph node and colon cancer)

Abstract Background This study aimed to identify the risk factors related in recurrence with isolated intra-abdominal lymph node metastasis in patients with colorectal cancer. Methods This is a retrospective, cross-sectional study of 21 colorectal cancer patients with isolated intra-abdominal lymph node metastases. Preoperative demographic and laboratory/postoperative histological features of these patients were been analyzed. Results Lymphovascular and perineural invasion and mutant-type K-ras status were more common in the study patients. In addition, a significant correlation was been detected between lymphovascular and perineural invasion, preoperative serum CEA level, preoperative thrombocyte count, mutant-type K-ras status, and pathological N3 disease. Mutant-type K-ras status and the presence of lymphovascular invasion were independent prognostic risk factors for isolated intra-abdominal lymph node metastasis. Conclusions The presence of lymphovascular invasion and mutant-type K-ras status may be poor prognostic risk factors for isolated intra-abdominal lymph node metastasis in patients with colorectal cancer. However, studies involving larger patient series, molecular indicators, and cohorts with metastasis in other areas are been needed to verify this study.

The prognostic role of lymphovascular invasion in urothelial carcinoma of the bladder.

Outcome prediction in patients with bladder cancer has improved through the development of nomograms and predictive models. However, integration of further characteristics such as lymphovascular invasion (LVI) might increase the accuracy and clinical utility of these instruments. Assessment and reporting of LVI in specimens from transurethral resection of the bladder tumour (TURBT) or biopsy in patients with non-muscle-invasive bladder cancer (NMIBC) or muscle-invasive bladder cancer (MIBC) might enable improved staging, prognostication and clinical decision-making. In NMIBC, presence of LVI in TURBT and biopsy samples seems to be associated with understaging and increased risks of disease recurrence and progression. In MIBC, presence of LVI is associated with features of aggressive disease and predicts recurrence and survival. Integration of LVI status into predictive models might aid clinical decision-making regarding intravesical instillation schedules and regimens, early radical cystectomy in patients with high-grade T1 disease and perioperative chemotherapy. However, LVI assessment is hampered by insufficient reproducibility and reliability, lack of routine evaluation and limited concordance between findings in TURBT and radical cystectomy specimens. Standardization of the pathological criteria defining LVI is warranted to improve its reporting in routine clinical practice and its utility as a care-changing prognostic marker.

Girdin (GIV) Expression as a Prognostic Marker of Recurrence in Mismatch Repair-Proficient Stage II Colon Cancer.

Prognostic markers that identify patients with stage II colon cancers who are at the risk of recurrence are essential to personalize therapy. We evaluated the potential of GIV/Girdin as a predictor of recurrence risk in such patients. Expression of full-length GIV was evaluated by IHC using a newly developed mAb together with a mismatch repair (MMR)-specific antibody panel in three stage II colon cancer patient cohorts, that is, a training (n = 192), test (n = 317), and validation (n = 181) cohort, with clinical follow-up data. Recurrence risk stratification models were established in the training cohort of T3, proficient MMR (pMMR) patients without chemotherapy and subsequently validated. For T3 pMMR tumors, GIV expression and the presence of lymphovascular invasion (LVI) were the only factors predicting recurrence in both training (GIV: HR, 2.78, P = 0.013; LVI: HR, 2.54, P = 0.025) and combined test and validation (pooled) cohorts (GIV: HR, 1.85, P = 0.019; LVI: HR, 2.52, P = 0.0004). A risk model based on GIV expression and LVI status classified patients into high- or low-risk groups; 3-year recurrence-free survival was significantly lower in the high-risk versus low-risk group across all cohorts [Training: 52.3% vs. 84.8%; HR, 3.74, 95% confidence interval (CI), 1.50-9.32; Test: 85.9% vs. 97.9%, HR, 7.83, 95% CI, 1.03-59.54; validation: 59.4% vs. 84.4%, HR, 3.71, 95% CI, 1.24-11.12]. GIV expression status predicts recurrence risk in patients with T3 pMMR stage II colon cancer. A risk model combining GIV expression and LVI status information further enhances prediction of recurrence. Further validation studies are warranted before GIV status can be routinely included in patient management algorithms. Clin Cancer Res; 22(14); 3488-98. ©2016 AACR.

Can lymphovascular invasion replace the prognostic value of lymph node involvement in patients with upper tract urothelial carcinoma after radical nephroureterectomy?

This study aimed to evaluate whether lymphovascular invasion (LVI) can replace lymph node (LN) involvement as a prognostic marker in patients who do not undergo lymph node dissection (LND) during surgery in patients with upper tract urothelial carcinoma (UTUC). A total of 505 patients who underwent radical nephroureterectomy (RNU) were recruited from four academic centres and divided into four groups: node negative (N0, Group 1); node positive (N+, Group 2); no LND without LVI (NxLVI-, Group 3); and no LND with LVI (NxLVI+, Group 4). Patients in Group 2 had larger tumours, a higher incidence of left-sided involvement, more aggressive T stage and grade, and a higher positive surgical margin rate than patients in other groups. Pathological features (T stage and grade) were poorer in Group 4 than in Groups 1 and 3. Compared to other groups, Group 2 had the worst prognostic outcomes regarding locoregional/distant metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS). LVI and LN status in Group 4 was not associated with MFS in multivariate analysis. Among Nx diseases, LVI was not an independent predictor of MFS or CCS. The small number of cases in Groups 2 and 4 is a major limitation of this study. Clinical outcomes according to LVI did not correlate with those outcomes predicted by LN involvement in patients with UTUC. Therefore, LVI may not be used as a substitute for nodal status in patients who do not undergo LND at the time of surgery.

Patterns of Recurrence in Upper Tract Transitional Cell Carcinoma: Imaging Surveillance.

The objective of our study was to evaluate recurrence patterns of upper tract transitional cell carcinomas (UT-TCCs) after radical nephroureterectomy (RNU). Sixty-eight patients (mean age, 78 years; 34 men and 34 women) with UT-TCC after having undergone RNU from 2001 to 2008 were included in this study. Radiologic examinations and clinical notes were reviewed to record tumor location, tumor morphology, histologic T stages and grades, lymphovascular invasion (LVI) status, and surgical procedures. Five-year imaging and clinical follow-up (2001-2013) findings were noted at 3, 6, 12, 18, 24, 36, 48, 60, and more than 60 months after RNU for recurrence pattern and tumor-free survival. Kaplan-Meier survival curves and Cox regression models were used to assess tumor-free survival and to perform a multivariate analysis. Forty-one postoperative recurrences were noted in 20 patients. The mean time to relapse was 16 months, and time to relapse ranged from 1 to 66 months. Tumor site (multifocal lesions involving both renal collecting system and ureter), tumor morphology (mass), T stage (muscle invasion [T2-T4]), histologic grade (grade 3), and the presence of LVI were identified as risk factors for postoperative recurrence in UT-TCC. T stage was the only independent risk factor. Urinary tract, lymph node, liver, bone, and lung recurrences were common in patients with UT-TCC and were detected most frequently at 3-24 months. Tumor site, tumor morphology, T stage, grade, and LVI status were associated with recurrence after RNU. T stage was the only independent predictor of tumor-free survival. Close surveillance for extra-urinary tract recurrences in high-risk groups and a shorter-interval follow-up of the urinary tract in low-risk patients with adjuvant chemotherapy are recommended. Identifying recurrence patterns in UT-TCC can aid in planning an effective tailored imaging surveillance strategy.

Prognostic Significance of Transverse Relaxation Rate (R2*) in Blood Oxygenation Level-Dependent Magnetic Resonance Imaging in Patients with Invasive Breast Cancer

ObjectiveTo examine the relationship between magnetic resonance transverse relaxation rate (R2*) and prognostic factors.Materials and MethodsA total of 159 women with invasive ductal carcinomas (IDCs) underwent breast magnetic resonance imaging (MRI) including blood oxygenation level-dependent (BOLD) sequence at 3 T. The distribution of the measured R2* values were analyzed, and the correlation between R2* and various prognostic factors (age, tumor size, histologic grade, lymphovascular invasion, and axillary lymph node status, as well as expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, p53, and Ki-67) were retrospectively assessed using patient medical records.ResultsThe baseline R2* values of the IDCs were very heterogeneous with wide range among the patients. The mean R2* value was (32.8 ± 14.0) Hz with a median of 29.3 Hz (range 13.5–109.4 Hz). In multivariate analysis, older age was associated with decreased R2* value (P = 0.011) and IDCs with p53-overexpression showed higher R2* values than those without p53-overexpression group (P = 0.031). Other prognostic factors were not significantly correlated with R2* value.ConclusionIn this study, R2* values were significantly correlated with age and expression of p53. Further studies are necessary to determine the prognostic value of BOLD-MRI.

Predictors of 5-year local, regional, and distant recurrent events in a population-based cohort of breast cancer patients

BackgroundThe study purpose was to identify tumor and surgeon predictors of local recurrence (LR), regional recurrence (RR), and distant metastasis (DM) after breast cancer (BC) surgery in a population-based cohort. MethodsConsecutive BC surgical cases from 12 hospitals in South Central Ontario between May 2006 and October 2006 were included. Data collected on chart review included patient and tumor factors, surgery type, adjuvant treatment, surgeon specialty, surgeon case volume, and practice type. Univariate and multivariable survival analyses were performed. ResultsMedian follow-up was 5.5 years for 402 patients (97% of sample). LR, RR, and DM occurred in 18 (4.5%), 10 (2.5%), and 47 (12%) patients, respectively. Significant predictors of BC recurrence (LR or RR or DM) were tumor size and grade, nodal status, and lymphovascular invasion on multivariable analysis. ConclusionTumor factors such as size, grade, lymphovascular invasion, and nodal status predicted BC recurrence, while practice type, surgeon specialty, and case volume did not.

Clinical and Pathological Factors Affecting the Sentinel Lymph Node Metastasis in Patients with Breast Cancer.

Sentinel lymph node biopsy has become the routine procedure in axilla-negative breast cancer patients at most medical centers for axillary staging and local control in the recent years. Sentinel lymph node is the only focus in axillary lymph metastasis in a large portion of patients. In our trial, we investigated the clinical and pathological factors that affect the positive status of sentinel lymph node. We included 89 patients, who underwent sentinel lymph node biopsy (SLNB) with methylene blue and/or technetium-99m Sulphur Colloid due to early-stage breast cancer. Five patients, in whom SLN was not detected and who underwent axillary dissection, were excluded from the trial. The patient age, location of the tumor, the type of the tumor, the T stage by the TNM staging system, the histological grade and type of the tumor, the status of multifocality, the lymphovascular invasion status of the tumor, and the ER, PR, and HER-neu2 status were recorded. The median age of the 89 patients was 52, 9 (±10) years. Fifty-seven (64%) and 32 (36%) of the 89 patients were detected to have positive and negative SLN, respectively. Assessing the SLNB positivity and the patient age, tumor size, tumor grade, multifocality, tumor localization, the T stage by the TNM staging, the ER/PR positivity/negativity, and the HER/neu2 and p53 status, the data revealed no statistically significant results with respect to SLN metastasis. The lymphovascular invasion status (LVI) was observed to statistically affect the SLN positivity (p < 0.016). We showed that LVI could be an important marker in predicting the SLN positivity in patients with axilla-negative early-stage breast cancer. In the future, upon introduction of new biomarkers and with relevant studies, it may be possible to predict the SLNB status of patients at an adequately high accuracy and a low risk.

Prognostic factors and predictive tools for upper tract urothelial carcinoma: a systematic review.

Upper tract urothelial carcinoma (UTUC) is a rare and heterogeneous disease. Several clinical and biological prognostic factors have been identified in multi-institutional collaborative works with the aim of helping decision-making in pursuit of tailored individual patient care. This review provides an overview of these existing prognostic factors and predictive tools for the management of patients with UTUC. A systematic literature search was performed using PubMed/MEDLINE, Web of Science and Scopus databases regarding articles published in English between January 2000 and November 2015 according to PRISMA guidelines. Thresholds of 100 and 300 patients were applied for studies on biomarkers and clinical studies, respectively. All the studies on predictive tools were included for analysis. Outcomes of interest were features associated with advanced-stage UTUC, disease recurrence and survival. A total of 116 studies were included in this review. These large and/or multi-institutional studies have confirmed the prognostic value of standard pathological factors (i.e., tumor stage, grade and lymph node metastasis) and identified novel features such as lymphovascular invasion, tumor architecture, multifocality, concomitant CIS, variant histology and biomarker status among others. Based on these variables, several predictive tools have been developed; however, they often lack of validation. The value of these features and tools needs prospective testing. Efforts provided by international collaboration groups have permitted to validate established features and identify new features of biologically and clinically aggressive UTUC. Further investigation on prognostic factors and biomarkers is still needed to assess the benefit of these features and tools on clinical decision-making.

Higher expression of EpCAM is associated with poor clinical and pathological responses in breast cancer patients undergoing neoadjuvant chemotherapy.

Neoadjuvant chemotherapy (NAC) is a standard regimen in treatment of breast cancer patients, but some are resistant to NAC. We hypothesized that breast cancer cells overexpressing epithelial cell adhesion molecule (EpCAM) could be resistant to NAC, contributing to a poor prognosis. Seventy patients with breast cancer were treated with NAC. Core needle biopsy (CNB) specimens and resected tumors before and after NAC, respectively, were examined for expression of EpCAM. In resected tumors, high EpCAM expression correlated with lymphovascular invasion status and nuclear grade (P = 0.01 and 0.008, respectively), and was associated with poor pathological and clinical responses (P < 0.001). High tumoral EpCAM expression in resected tumor was independently related to a poor pathological response. Patients with high EpCAM expression before and after NAC (high-to-high group) showed worse pathological and clinical responses (P = 0.008 and <0.001, respectively) than the patients with high and low EpCAM expression before and after NAC, respectively (high-to-low group). The overall survival rate of the high-to-high group appeared shorter compared with the high-to low-group (P = 0.049). Our findings imply that higher levels of EpCAM in breast cancer may be associated with poor response to NAC via a potential chemoresistant effect.

Association between preoperative serum total cholesterol level and biochemical recurrence in prostate cancer patients who underwent radical prostatectomy.

The aim of this study was to investigate the association between serum total cholesterol (TC) level and biochemical recurrence (BCR) following radical prostatectomy (RP). The study included 562 patients with T1-3N0M0 prostate cancer, who underwent RP at our institution between 2002 and 2010. No patients received neoadjuvant and/or adjuvant therapy. The associations between preoperative TC level, clinicopathological factors and BCR were assessed using univariate and multivariate analyses. During follow-up (mean, 54.0 months), 168 patients (168/562, 29.9%) experienced BCR, with a 5-year BCR-free rate of 67.2%. Of the clinicopathological characteristics investigated, statin use and lymphovascular invasion (LVI) status were associated with lower TC level (P=0.003 and P=0.014, respectively). In the univariate analysis, a higher serum prostate-specific antigen (PSA) level at diagnosis, extracapsular extension, positive surgical margin, seminal vesicle invasion, LVI, perineural invasion, higher Gleason score (GS ≥8) based on the RP specimen, increased body mass index, and low preoperative TC level, were significantly associated with BCR. In the multivariate analysis, the TC level was an independent predictor of BCR (hazard ratio = 0.925 per 10 mg/dl; 95% confidence interval: 0.879-0.973; P=0.003), as was the serum PSA level, extracapsular extension, positive surgical margin and the GS. Low preoperative serum TC levels were associated with an increased risk of BCR among prostate cancer patients who underwent RP. Our findings suggest that the preoperative serum TC level may provide important clinical information that may prove to be useful in patient counseling.

Ezrin contributes to cervical cancer progression through induction of epithelial-mesenchymal transition.

Cervical cancer is the third most common cancer in females worldwide. The treatment options for advanced cervical cancer are limited, leading to high mortality. Ezrin is a membrane-cytoskeleton-binding protein recently reported to act as a tumor promoter, and we previously indicated that the aberrant localization and overexpression of Ezrin could be an independent effective biomarker for prognostic evaluation of cervical cancers. In this study, we identified Ezrin as a regulator of epithelial-mesenchymal transition (EMT) and metastasis in cervical cancer. Ezrin knock-down inhibited anchorage-independent growth, cell migration, and invasion of cervical cancer cell lines in vitro and in vivo. EMT was inhibited in Ezrin-depleted cells, with up-regulation of E-cadherin and Cytokeratin-18 (CK-18) and down-regulation of mesenchymal markers. Ezrin knock-down also induced Akt phosphorylation. These results implicate Ezrin as an EMT regulator and tumor promoter in cervical cancer, and down-regulation of Ezrin suppressed cervical cancer progression, possibly via the phosphoinositide 3-kinase/Akt pathway. Furthermore, the expression pattern of Ezrin protein was closely related with the lymphovascular invasion status of cervical cancer by immunohistochemistry, and the survival analysis revealed that the cervical cancer patients with the perinuclear Ezrin expression pattern had longer survival time than those with the cytoplasmic Ezrin expression pattern. Ezrin thus represents a promising target for the development of novel and effective strategies aimed at preventing the progression of cervical cancer.