Predictors Of Lymph Node Involvement Research Articles

Abstract A09: A next generation sequencing based microsatellite instability assay suitable for routine risk stratification in colorectal cancer

Abstract 3-5% of CRCs show microsatellite instability (MSI) caused by germline defects in mismatch repair genes (MMR) predisposing to Lynch syndrome. In addition, 12% of sporadic CRCs show MSI. Currently, MSI is tested using a fragment analysis based assay not suitable for high throughput testing with suboptimal sensitivity and specificity. Knowledge of microsatellite instability affects prognosis (MSI is a positive prognostic factor in stage II CRC), risk stratification (for the affected and at risk relatives in Lynch syndrome), prediction of lymph node involvement (lymph node metastasis is unlikely in stage I MSI positive CRC) and treatment of CRCs (MMR deficient tumours showed observable benefit from PD-1 blocking agent pembrolizumab). For all these important benefits, MSI testing is now recommended for all newly diagnosed CRCs. As a result, development of a high throughput approach is desirable. We have developed and validated a high throughput sequence based MSI assay. In this study, we tested 17 short (7-12bp) mononucleotide markers (previously identified by our team via an in silico analyses of whole genome sequencing data). These 17 markers were able to discriminate between MSI-high (MSI-H) and microsatellite stable (MSS) cases. To define the optimal parameters to discriminate between MSI-H and MSS samples, we tested these 17 markers across a panel of 141 CRC samples. This allowed us to define a scoring scheme for the 17 markers using allelic imbalance based on a linked SNP (called weighted scoring scheme), which achieved 96% sensitivity and 100% specificity. This scoring scheme was then validated using an independent cohort of 70 CRCs without knowing their MSI status. The assay achieved a 100% sensitivity and specificity. We provide here a high throughput tool to detect microsatellite instability that is less costly, uses short mononucleotide markers (eliminating the need to test matched normal tissue) and is validated on formalin fixed paraffin embedded (FFPE) samples (similar to routine samples). The ability to test the microsatellite instability status in all the newly diagnosed CRC cases would have a great clinical impact on prognosis, risk stratification and treatment of CRCs. Citation Format: Ghanim Alhilal, Lisa Redford, Angel Alonso, Sira Moreno, Mark Arends, Anca Oniscu, Ottilia O'Brien, Stephanie Needham, John Burn, Michael Jackson, Mauro Santibanez-Koref. A next generation sequencing based microsatellite instability assay suitable for routine risk stratification in colorectal cancer. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr A09.

471 Predictors of Lymph Node Involvement in Early Stage Gastric Adenocarcinoma in the United States

471 Predictors of Lymph Node Involvement in Early Stage Gastric Adenocarcinoma in the United States

Predictors for lymph nodes involvement in low risk endometrial cancer

Neutrophil–lymphocyte ratio (NLR) and BMI were examined as pre-operative predictors for lymph node metastases in patients with low-risk endometrial cancer. The study was a retrospective analysis of 534 endometrial cancer patients that underwent hysterectomy and lymph node dissection. Included subjects had a preoperative diagnosis of a grade 1 or 2 endometrioid carcinoma and no macroscopic extrauterine disease. We compared node-negative to node-positive patients to identify correlates of node-positive disease. The node-positive group presented with lower BMI than the node-negative group, 31.5 and 34.4, respectively (p = .03). The mean NLR was higher in the node-positive group 3.4 vs 2.9 (p = .08), showing a trend towards significance on univariate analysis. On multivariate analysis, lower BMI was found to be an independent predictor for nodal metastasis. Our data suggest that lower BMI is a risk factor for lymph nodes involvement in low-risk endometrial cancer.Impact statementMost endometrial cancer patients have low-risk disease with low risk for lymph nodes metastasis. In order to reduce the number of patients that will undergo unnecessary lymph node dissection, different types of preoperative predictors for lymph node involvement were studied. CA 125 and different imaging modalities were found as useful predictors for more advanced disease. Less studied predictors are the systemic inflammatory response markers and patient’s BMI. This study suggests that lower BMI is a risk factor for lymph node involvement in low-risk endometrial cancer. The neutrophil to lymphocyte ratio was close to significance as a predictor for lymph node involvement. In practice, physicians might favour comprehensive lymph node dissection when there is a doubt regarding the procedure but the patient is lean. The study’s conclusion can be utilised for triaging patients to general gynaecologist vs gynaecologic oncologist. Further research should focus on combining predictors such as age, BMI, NLR, CA 125 and imaging to better predict lymph nodes involvement in low-risk endometrial cancer.

Prognostic risk factors for lymph node involvement in patients with endometrial cancer.

Objective:We aimed to analyze variables affecting lymph node (LN) involvement and to assess the need for systematic lymphadenectomy in patients with endometrial cancer (EC).Materials and Methods:A single centre retrospective analysis was conducted in a total of 128 consecutive patients with EC who underwent systematic pelvic or combined pelvic and paraaortic lymphadenectomy between 2009 and 2012. Mann-Whitney U, chi-square, and Fisher’s exact test were used for univariate analyses when appropriate. Variables with a p value <0.05 in the univariate analysis were included into a multivariate logistic regression analysis. The effects of variables on LN involvement are reported using adjusted odds ratios (ORs) and 95% confidence intervals (CI).Results:In univariate analysis, grade 2-3, tumor size ≥3 cm, deep (≥50%) myometrial invasion, presence of cervical, adnexal or omental involvement, positive peritoneal cytology, open surgical approach (laparotomy), combined pelvic and paraaortic lymphadenectomy and number of total LNs removed (>30) were found associated with LN involvement. However, the number of total LNs removed (>30) was the only independent variable that predict LN involvement in multivariate analysis [OR: 15.08; 95% CI: (1.28-177.59); p=0.03].Conclusion:This study demonstrates that the more LNs removed during staging of EC, the greater the probability of finding LN metastasis.

Lymphocyte-to-monocyte ratio and neutrophil-to-lymphocyte ratio as biomarkers for predicting lymph node metastasis and survival in patients treated with radical cystectomy.

To evaluate the role of lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR) as pre-operative markers for predicting extravesical disease and survival outcomes in patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). Data from 4335 patients undergoing RC for clinically non-metastatic UCB were analyzed. Multivariable logistic regression models were used to predict lymph node involvement and extravesical disease (defined as ≥pT3 and N0). Recurrence-free (RFS), cancer-specific (CSS), and overall survival (OS) were evaluated using multivariable Cox models. The accuracy of the models was assessed with receiver operating characteristics (ROC) curves and concordance-index. Median LMR was 3.5 and median NLR was 2.7. Addition of LMR and NLR to a standard preoperative model improved its discrimination for prediction of lymph node metastasis by 4.5%. On multivariable analysis LMR and NLR independently predicted RFS, CSS, and OS. The discrimination of this model increased by adding LMR and NLR but was not significant. LMR and NLR independently improved the preoperative prediction of lymph node metastasis and survival outcomes. As they are readily available, they could be integrated in a panel of preoperative markers helping selecting patients who have extravesical lymph node involvement and more aggressive disease.

P1.07-042 Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios Predict Prognosis in Early-Stage Resected Small-Cell Lung Cancer Patients

Surgical resection is rarely possible in small-cell lung cancer (SCLC), a highly aggressive malignancy with limited treatment options. However, although in the past decades, for selected early-stage cases, a curative intent surgery is often performed, there is no biomarker to help the selection of patients eligible for surgery. Because previous studies - predominantly from East Asia - showed that high neutrophil to lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) correlate with poor prognosis in several types of tumors including SCLC, the aim of our study was to investigate the prognostic value of NLR and PLR in Caucasian patients with resected SCLC. Consecutive patients with histologically confirmed and surgically resected SCLC evaluated between 2000 and 2013 at the National Koranyi Institute of Pulmonology were analyzed in this retrospective analysis. Patients were divided into “high” and “low” groups according to their NLR and PLR at diagnosis. The cut-off NLR and PLR values were 3 and 110, respectively. Next, we evaluated the associations of preoperative NLR or PLR with vascular involvement, tumor necrosis, peritumoral inflammation, tumor grade, clinicopathological characteristics (including age, gender, stage) and overall survival (OS) in univariate and multivariate analyses. There were a total of 65 patients (39 men and 26 women) with a median age of 57.7 years (range, 40-79). The pathological stages were 1, 2 and 3A in 23, 23 and 14 cases by AJCC 7th edition (in five patients no pTNM was available). PLR was high (HPLR) in 41 (63%) and low (LPNR) in 24 (37%) patients. NLR was high (HNLR) in 35 (66%) and low (LLNR) in 17 (33%) patients. PLR significantly correlated with pathologic lymph node status (p<0.001) and NLR (p=0.007). HPLR was associated with shorter OS (vs. LPLR, HR, 2.2; 95% CI, 1.13–4.29; p=0.02). There was a non-significant trend towards longer OS in patients with LNLR (vs. HNLR, p=0.078). There were no significant associations between NLR or PLR and age, gender, stage, vascular involvement, tumor necrosis, peritumoral inflammation and tumor grade. This is the first study in Caucasian patients with resected SCLC which shows that LPLR (<110) before surgical resection may be a favorable prognostic factor for longer OS. We also conclude that preoperative HPLR may predict lymph node involvement. PLR but not NLR may help in selecting patients for surgery in the future. Further prospective studies are needed to confirm these observations.

Improving the Prediction of Lymph Node Involvement in Patients With Prostate Adenocarcinoma by Incorporating Percent Positive Cores

Improving the Prediction of Lymph Node Involvement in Patients With Prostate Adenocarcinoma by Incorporating Percent Positive Cores

Association of the preoperative neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios with lymph node metastasis and recurrence in patients with medullary thyroid carcinoma.

The preoperative neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are known to be prognostic factors in several cancers. However, no previous investigation has been performed to evaluate the significance of the NLR and PLR in medullary thyroid carcinoma (MTC).The aim of this study was to identify the ability of the preoperative NLR or PLR to predict lymph node metastasis and recurrence in patients with MTC. Data from all patients with MTC who had undergone surgery at our institution from May 2009 to May 2016 were retrospectively evaluated. Receiver operating characteristic (ROC) analysis was performed to identify optimal NLR and PLR cutoff points, and we assessed independent predictors of lymph node metastasis and recurrence using univariate and multivariate analyses.Based on the inclusion and exclusion criteria, a total of 70 patients were enrolled in this study. The ideal cutoff points for predicting lymph node involvement were 2.7 for the NLR and 105.3 for the PLR. The optimal cutoff points of the NLR and PLR for predicting recurrence were 2.8 and 129.8, respectively. Using the cutoff values, we found that PLR>105.3 (odds ratio [OR] 4.782, 95% confidence interval [CI] 1.4–16.7) was an independent predictor of lymph node metastasis and that PLR>129.8 (OR 3.838, 95% CI 1.1–13.5) was an independent predictor of recurrence.Our study suggests that the preoperative PLR, but not NLR, was significantly associated with lymph node metastasis and recurrence in patients with MTC.

Treatment allocation in patients with early-stage esophageal adenocarcinoma: Prevalence and predictors of lymph node involvement.

In considering treatment allocation for patients with early esophageal adenocarcinoma, the incidence of lymph node metastasis is a critical determinant; however, this has not been well defined or stratified by the relevant clinical predictors of lymph node spread. Data from the Surveillance, Epidemiology, and End Results database of the National Cancer Institute were abstracted from 2004 to 2010 for patients with early-stage esophageal adenocarcinoma. The incidence of lymph node involvement for patients with Tis, T1a, and T1b tumors was examined and was stratified by predictors of spread. A total of 13,996 patients with esophageal adenocarcinoma were evaluated. Excluding those with advanced, metastatic, and/or invasive (T2-T4) disease, 715 patients with Tis, T1a, and T1b tumors were included. On multivariate analysis, tumor grade (odds ratio [OR], 2.76; 95% confidence interval [95% CI], 1.58-4.82 [P<.001]), T classification (OR, 0.47; 95% CI, 0.24-0.91 [P =.025]), and tumor size (OR, 2.68; 95% CI, 1.48-4.85 [P = .001]) were found to be independently associated with lymph node metastases. There was no lymph node spread noted with Tis tumors. For patients with low-grade (well or moderately differentiated) tumors measuring <2 cm in size, the risk of lymph node metastasis was 1.7% for T1a (P<.001) and 8.6% for T1b (P = .001) tumors. For patients with low-grade Tis or T1 tumors measuring ≤2 cm in size, the incidence of lymph node metastasis appears to be comparable to the mortality rate associated with esophagectomy. For highly selected patients with early esophageal adenocarcinomas, the results of the current study support the recommendation that local endoscopic resection can be considered as an alternative to surgical management when followed by rigorous endoscopic and radiographic surveillance. Cancer 2016;122:2150-7. © 2016 American Cancer Society.

Association of P53 Protein Overexpression with Clinicopathological Features of Oral Squamous Cell Carcinoma Patients in Bali

Background: Oral cancer was a major health problem with a high incidence rate worldwide. Oral Squamous Cell Carcinoma (OSCC) in Bali, ranked as the second most common cancer after cervix carcinoma. Our understanding of OSCC hasn’t yielded a satisfactory clinical outcome; therefore, further studies about the role of biomolecular markers in OSCC are still needed. One of the biomolecular markers for prognosis and predictor for OSCC that has been a topic of research to date is p53. Method: This is a cross-sectional analytical study of 36 samples to determine the correlation between p53 overexpression with age group, tumor location, tumor stage, and tumor grade in OSCC patients. Data was processed descriptive and analytical using Chi-Square/Fisher 's Exact Test methods with a significance value of p <0.05 was considered significant. Results: From the 36 samples collected, the mean age was 55,19±14,712 years, 19 samples (52.8%) were women, 21 samples (58,3%) were ?60 years, 24 samples (66,7%) had OSCC on the postero inferior region, 19 samples (52,8%) were in high stage group, 22 samples (61,1%) had high grade OSCC, and 22 samples (61,1%) showed high p53 overexpression. There were significant differences in proportion between OSCC grade with p53 expression (Chi-square test p=0,013; r=0,416; OR=6,12 CI=95%) and between OSCC N stage with p53 expression (Fisher's Exact Test p=0,024; r=0,396; OR=6,33 CI=95%). Conclusion: There were significant differences in the proportion between OSCC grade and N stage with p53 expression. Therefore, p53 overexpression can be used as a prognostic indicator and predictor of lymph node involvement in OSCC.

MP90-20 IMPLICATIONS OF SOX2 STAINING IN HIGH GRADE PROSTATE CANCER AND PELVIC LYMPH NODE METASTASES REMOVED AT RADICAL PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology IV1 Apr 2016MP90-20 IMPLICATIONS OF SOX2 STAINING IN HIGH GRADE PROSTATE CANCER AND PELVIC LYMPH NODE METASTASES REMOVED AT RADICAL PROSTATECTOMY Blake Anderson, Charles Nottingham, Steven Kregel, Gregory Zagaja, Gladell Paner, and Donald Vander Griend Blake AndersonBlake Anderson More articles by this author , Charles NottinghamCharles Nottingham More articles by this author , Steven KregelSteven Kregel More articles by this author , Gregory ZagajaGregory Zagaja More articles by this author , Gladell PanerGladell Paner More articles by this author , and Donald Vander GriendDonald Vander Griend More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2564AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The transcription factor Sox2 has been shown to promote castrate-resistant prostate cancer (PCa) and has been associated with higher stage disease in radical prostatectomy (RP) specimens. Our goal was to determine if Sox2 could predict lymph node involvement or worse outcomes for patients with PCa who underwent RP. METHODS Using an institutional database, 22 patients were identified with node positive disease (N1) identified at RP, and 22 node negative controls (N0) were identified for comparison. Four patients in N1 were excluded due to unavailable specimens. Baseline characteristics were collected. The primary outcome was Sox2 positivity in prostate tumor specimens (staining in ≥1-10% of PCa cells). Within N1, 14 available lymph node specimens were stained for Sox2, and oncologic outcomes were compared between those with and without Sox2 staining. Percent staining of Sox2 was determined independently by a genitourinary pathologist blinded to clinical information. Statistical tests performed were Fisher′s exact and two sample t-tests. RESULTS Forty patients who underwent RP between 2004 and 2012 were analyzed, with 18 (45%) in N1 and 22 (55%) in N0. No differences were seen between N1 and N0 in mean age at RP (59.4 ± 7.2 vs. 62.4 ± 6.5, p=0.2), race (p=0.6), preoperative PSA (12.5 ± 7.5 vs. 12.0 ± 11.1, p=0.9), Gleason score (≈1.0), pathologic stage (5% T2, 39% T3a, 56% T3b vs. 5% T2, 45% T3a, 50% T3b, p=0.9) or positive margin rate (50% vs. 65%, p=0.52). BMI was higher for N1 compared to N0 (31.6 ± 7.4 vs. 27.5 ± 4.5, p=0.04). Overall, Sox2 positivity was not significantly increased for N1 compared to N0 (67% vs. 55%, p=0.5), but moderate (11-50% staining) was significantly higher for N1 compared to N0 (28% vs. 4.6%, p=0.04). On multivariable analysis, specimens with positive margins were twice as likely to stain positive for Sox2 (OR: 1.96, 95% CI: 0.003-3.280), but patients with higher BMI or nodal disease were not associated with Sox2 positivity (OR: 1.14, 95% CI: -0.06-0.23, OR: 0.49, 95% CI: -1.22-2.04). For the 14/18 (78%) patients in N1 whose lymph nodes were stained, 4/14 (29%) were Sox2 positive, and all 4 came from Sox2 positive tumors (p=0.001). One patient (25%) with positive nodes staining for Sox2 developed castrate-resistance and ultimately died of PCa 50 months after RP. CONCLUSIONS While N1 disease at RP was not associated with Sox2 positivity, both N1 and N0 disease Sox2 staining conferred a significant correlation with positive margins. Future studies are needed to demonstrate the impact of Sox2 positive nodes on prognosis after RP. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1152 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Blake Anderson More articles by this author Charles Nottingham More articles by this author Steven Kregel More articles by this author Gregory Zagaja More articles by this author Gladell Paner More articles by this author Donald Vander Griend More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Estrogen receptor-alpha as a predictive biomarker in endometrioid endometrial cancer

BackgroundWe sought to validate the prognostic significance of estrogen receptor alpha (ERα) expression and to investigate the relationship between ESR1 mutation status and outcomes in a large cohort of patients with endometrial cancer. We also investigated the predictive value of ERα for lymph node involvement in a large surgically staged cohort. MethodsA tumor microarray (TMA) was constructed including only pure endometrioid adenocarcinomas, stained with ER50 monoclonal antibody, and assessed using digital image analysis. For mutation analysis, somatic DNA was extracted and sequenced for ESR1 gene hotspot regions. Differences in patient and tumor characteristics, recurrence and survival between ERα positive and negative, mutated and wild-type tumors were evaluated. ResultsSixty (18.6%) tumors were negative for ERα. Absence of ERα was significantly associated with stage and grade, but not with disease-free or overall survival. ERα was a strong predictor of lymph node involvement (RR: 2.37, 95% CI: 1.12–5.02). Nineteen of 1034 tumors (1.8%) had an ESR1 hotspot mutation; twelve in hotspot 537Y, four in 538D and three in 536L. Patients with an ESR1 mutation had a significantly lower BMI, but were comparable in age, stage and grade, and progression-free survival. ConclusionPatients with ERα negative endometrioid endometrial cancer are more often diagnosed with higher grade and advanced stage disease. Lymph node involvement is more common with lack of ERα expression, and may be able to help triage which patients should undergo lymphadenectomy. Mutations in ESR1 might explain why some low risk women with low BMI develop endometrial cancer.

Is there still a role for computed tomography and bone scintigraphy in prostate cancer staging? An analysis from the EUREKA-1 database.

According to the current guidelines, computed tomography (CT) and bone scintigraphy (BS) are optional in intermediate-risk and recommended in high-risk prostate cancer (PCa). We wonder whether it is time for these examinations to be dismissed, evaluating their staging accuracy in a large cohort of radical prostatectomy (RP) patients. To evaluate the ability of CT to predict lymph node involvement (LNI), we included 1091 patients treated with RP and pelvic lymph node dissection, previously staged with abdomino-pelvic CT. As for bone metastases, we included 1145 PCa patients deemed fit for surgery, previously staged with Tc-99m methylene diphosphonate planar BS. CT scan showed a sensitivity and specificity in predicting LNI of 8.8 and 98 %; subgroup analysis disclosed a significant association only for the high-risk subgroup of 334 patients (P 0.009) with a sensitivity of 11.8 % and positive predictive value (PPV) of 44.4 %. However, logistic multivariate regression analysis including preoperative risk factors excluded any additional predictive ability of CT even in the high-risk group (P 0.40). These data are confirmed by ROC curve analysis, showing a low AUC of 54 % for CT, compared with 69 % for Partin tables and 80 % for Briganti nomogram. BS showed some positivity in 74 cases, only four of whom progressed, while 49 patients with negative BS progressed during their follow-up, six of them immediately after surgery. According to our opinion, the role of CT and BS should be restricted to selected high-risk patients, while clinical predictive nomograms should be adopted for the surgical planning.

First Nomogram Predicting the Probability of Lymph Node Involvement in Prostate Cancer Patients Undergoing Radioisotope Guided Sentinel Lymph Node Dissection

Introduction: Existing nomograms predicting lymph node involvement (LNI) in prostate cancer (PCa) are based on conventional lymphadenectomy. The aim of the study was to develop the first nomogram for predicting LNI in PCa patients undergoing sentinel guided pelvic lymph node dissection (sPLND). Materials and Methods: Analysis was performed on 1,296 patients with PCa who underwent radioisotope guided sPLND and retropubic radical prostatectomy (2005-2010). Median prostate specific antigen (PSA): 7.4 ng/ml (IQR 5.3-11.5 ng/ml). Clinical T-categories: T1: 54.8%, T2: 42.4%, T3: 2.8%. Biopsy Gleason sums: ≤6: 55.1%, 7: 39.5%, ≥8: 5.4%. Multivariate logistic regression models tested the association between all of the above predictors and LNI. Regression-based coefficients were used to develop a nomogram for predicting LNI. Accuracy was quantified using the area under the curve (AUC). Results: The median number of LNs removed was 10 (IQR 7-13). Overall, 17.8% of patients (n = 231) had LNI. The nomogram had a high predictive accuracy (AUC of 82%). All the variables were statistically significant multivariate predictors of LNI (p = 0.001). Univariate predictive accuracy for PSA, Gleason sum and clinical stage was 69, 75 and 69%, respectively. Conclusions: The sentinel nomogram can predict LNI at a sPLND very accurately and, for the first time, aid clinicians and patients in making important decisions on the indication of a sPLND. The high rate of LN+ patients underscores the sensitivity of sPLND.

Retrospective preoperative assessment of the axillary lymph nodes in patients with breast cancer and literature review

To evaluate the accuracy of axillary ultrasound, compared with published literature, identify women at low risk for lymph node (LN) involvement, and to determine which clinical, pathological, and imaging findings best predict LN involvement. From June 2010 to April 2012, 288 women with breast lesions that were suspicious of malignancy (category 4) or malignant (category 5) underwent axillary ultrasound examination. A 3mm LN cortical thickness was used as the threshold to prompt fine-needle aspiration biopsy (FNAB) of the LN. Data were gathered regarding size, site, and grade of the index breast lesion and cortical thickness of the LN. Using a cut-off point of <3mm versus ≥3mm, abnormal cortical thickness had a sensitivity and specificity of 56.3% and 86.7%, respectively. Breast cancer size was significantly associated with the odds of LN metastasis (p<0.001). There were 69 patients with breast cancers of ≤10mm and 18% had positive axillary LNs. A much higher rate of malignancy was observed in breast cancers located in multiple sites and in a central location. The likelihood of axillary LN metastasis increases with cortical thickness ≥3mm and this concurs with the literature. A low-risk group of women was identified with screen-detected, low-grade small cancers with LNs with a cortical thickness of <3mm. Additional features other than cortical thickness >3mm (such as shape [rounding], echogenicity [markedly hypo-echoic cortex], and morphology [hilar compressional displacement, loss of echogenic outer capsule and angular margins]) should be used to indicate FNAB in patients with a palpable lump, multiple or central cancers, and cancers >20mm.

Prediction of lymph node involvement in breast cancer using RNA-sequencing and microRNA expression profile.

e12558 Background: Evidence that microRNAs (miRNAs) regulate the various steps of metastasis is increasing. Several studies have looked at the miRNA expression profile in primary breast tumors but ...

Aberrant loss of dickkopf-3 in gastric cancer: can it predict lymph node metastasis preoperatively?

Dickkopf-3 (DKK3) may act as a tumor suppressor as it is down-regulated in various types of cancer. This study assessed the DKK3 protein expression in gastric cancer and its potential value as a prognostic marker. DKK3 expression was evaluated by immunohistochemistry in 158 gastric cancer samples from patients who underwent gastrectomy from 2002 to 2008. Clinicopathological parameters and survival data were analyzed. Loss of DKK3 expression was found in 64 of 158 (40.5%) samples, and it was associated with advanced T stage (p < 0.001), lymph node metastasis (p < 0.001), UICC TNM stage (p < 0.001), tumor location (p = 0.029), lymphovascular invasion (p = 0.035), and perineural invasion (p = 0.032). Patients without DKK3 expression in tumor cells had a significantly worse disease-free and overall survival than those with DKK3 expression (p < 0.001, and p = 0.001, respectively). TNM stage (p = 0.028 and p < 0.001, respectively) and residual tumor (p < 0.001 and p = 0.003, respectively) were independent predictors of disease-free and overall survival. Based on the preoperative clinical stage assessed by computed tomography (CT), loss of DKK3 expression was predominantly associated with worse prognosis in patients with clinically node-negative advanced gastric cancer (AGC). The combination of DKK3 expression status and CT increased the accuracy of CT staging for predicting lymph node involvement from 71.5 to 80.0% in AGC patients. Loss of DKK3 protein expression was significantly associated with poor survival in patients with gastric cancer and was strongly correlated with the TNM stage. DKK3 might be a potential biomarker of lymph node involvement that can improve the predictive power of CT.

The association between metabolic syndrome and advanced prostate cancer in Chinese patients receiving radical prostatectomy.

The global incidence of metabolic syndrome (MetS) is dramatically increasing. Considerable interest has been devoted to the relationship between MetS and prostate cancer (PCa) risk. However, few studies have examined the association between MetS and PCa progression. This retrospective study consisted of 1016 patients with PCa who received radical prostatectomy. The association between MetS and pathological features was evaluated using logistic regression analysis. Compared with patients without MetS, those with MetS indicated an increased risk of prostatectomy Gleason score (GS) ≥8 (odds ratio [OR] =1.670, 95% confidence interval (CI) 1.096–2.545, P= 0.017), and a 1.5-fold increased risk of pT3–4 disease (OR = 1.583, 95% CI 1.106–2.266, P= 0.012). The presence of MetS was an independent predictor of lymph node involvement (OR = 1.751, 95% CI 1.038–2.955, P= 0.036). Furthermore, as the number of MetS components accumulated, the risk of a GS ≥ 8 increased. The present study indicates a significant association between MetS and advanced PCa. The results need to be evaluated in large-scale prospective cohorts.

Evaluation of Effect of Lymph Node Involvement on Prognosis of Clear Cell Renal Cell Cancer and Role of Tumor Size and Grade on Prediction of Lymph Node Involvement

Evaluation of Effect of Lymph Node Involvement on Prognosis of Clear Cell Renal Cell Cancer and Role of Tumor Size and Grade on Prediction of Lymph Node Involvement

Prognostic and diagnostic value of epithelial to mesenchymal transition markers in pulmonary neuroendocrine tumors.

BackgroundPulmonary neuroendocrine tumors (Pulmonary NETs) include a wide spectrum of tumors, from the low-grade typical carcinoid (TC) and the intermediate-grade atypical carcinoid (AC), to the high-grade large-cell neuroendocrine carcinoma (LCNEC) and the small-cell carcinoma (SCLC). Epithelial Mesenchymal Transition (EMT) is a process initially recognised during several critical stages of embryonic development, which has more recently been implicated in promoting carcinoma invasion and metastasis. The initial stage of the EMT process begins with the deregulation of adhesion molecules, such as E-cadherin, due to transcriptional repression carried out by factors such as Snail family members, Twist and Foxc2.MethodsImmunohistochemistry for EMT markers and E-cadherin/ β-catenin complex in 134 patients with pulmonary NETs between 1990 – 2009. Analysis of potential associations with clinicopathological variables and survival.ResultsPulmonary NETs of high malignant potential (LCNEC and SCLC) had reduced expression of the adhesion molecules and high level expression of transcriptional repressors (Snail1, Snail2, Twist and Foxc2). Snail high expression levels and the loss of E-cadherin/β-catenin complex integrity had the strongest negative effect on the five-year survival rates. E-cadherin/β-catenin complex integrity loss independently predicted lymph node involvement and helped in Atypical Carcinoid (AC) vs Typical Carcinoid (TC) differential diagnosis. Importantly, among the TC group, the loss of E-cadherin/β-catenin complex integrity identified patients with an adverse clinical course despite favourable clinicopathological features.ConclusionThe immunohistochemical determination of E-cadherin/β-catenin complex integrity loss and EMT markers in the clinical setting might be a potential useful diagnostic and prognostic tool especially among the TC patients.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-855) contains supplementary material, which is available to authorized users.