Higher Number Of Positive Nodes Research Articles

P-OGC71 Five positive lymph nodes are a significant negative indicator of survival in Oesophago-Gastric Cancer surgery: an 8-year study

Abstract Background Number of positive lymph nodes involved is an important prognostic indicator in Oesophago-Gastric cancer survival post surgery. We present an 8 year study examining the number of lymph nodes involved and its impacts on long term cancer survival and in particular to determine whether there is a threshold after which survival is significantly worsened. Methods A prospectively maintained single-institution database containing data from all patients from Jan 2012 to Dec 2020 was analysed. Survival analyses were undertaken to determine the association between lymph node positivity and survival. Results A total of 430 patients underwent surgery for gastro-oesophageal cancer (oesophagectomy: n = 311, 72.3%; gastrectomy n = 119, 27.7%) of which 80.2% were male and the median age was 68 years old (IQR: 61-74). A median of 23 nodes were examined (IQR 18-33) and a median of one lymph node was positive for cancer (IQR 0-3 lymph nodes). The majority of patients (59.3%) had a T3 tumour, 24.0% had T2, and 12.1% had a T1 tumour. Over a median follow up of 30 months (IQR 13-61), 61.2% of the study population were alive. Kaplan Meier analyses demonstrated that patients who had five or more positive nodes had a survival of 36.3 months (IQR: 24.4-48.3 months) compared to those with four or fewer nodes (45.8 months, IQR: 27.6-64.1 months, p > 0.001). Survival did not worsen further with a higher number of positive nodes. Conclusions This study shows that having five or more positive lymph nodes significantly worsens Oesophago-gastric cancer survival. These results may suggest that from the threshold of 5 positive nodes, OG cancer behaves as a systemic disease and thus impact on adjuvant treatment strategies.

Extended Lymphadenectomy Improves Survival After Induction Chemoradiation for Esophageal Cancer: A Propensity-Matched Analysis of the National Cancer Database.

The aim of this study was to explore the potential value of extended nodal-dissection following neoadjuvant chemoradiation (CRT), by analyzing data from the National Cancer Database (NCDB). A CROSS-trial post-hoc analysis showed that the number of dissected lymph nodes was associated with improved survival in patients undergoing upfront surgery but not in those treated with neoadjuvant CRT. The NCDB was queried (2004-2014) for patients who underwent esophagectomy following induction CRT. Predictors of overall survival (OS) were assessed. The optimal number of dissected LNs associated with highest survival benefit was determined by multiple regression analyses and receiveroperating characteristic curve analysis. The whole cohort was divided into 2 groups based on the predefined cutoff number. The two groups were propensity-matched (PMs). Esophagectomy following induction-CRT was performed in 14,503 patients. The number of resected nodes was associated with improved OS in the multivariable analysis (hazard ratio for every 10 nodes: 0.95 (95% confidence interval: 0.93-0.98). The cutoff number of resected LNs that was associated with the highest survival benefit was 20 nodes. In the PM groups, patients in the "≥20 LNs" group had a 14% relative-increase in OS ( P = 0.002), despite having more advanced pathological stages (stage II-IV: 76% vs 72%, P < 0.001), and higher number of positive nodes (0-2 vs 0-1, P < 0.001). The total number of resected nodes is a significant determinant of improved survival following induction CRT in patients with either node negative or node positive disease. In the matched groups, patients with higher number of resected lymph nodes had higher OS rate, despite having more advanced pathological disease and higher number of resected positive lymph nodes.

Is extracapsular nodal extension in sentinel nodes a predictor for nonsentinel metastasis and is there an impact on survival parameters?-A retrospective single center cohort study with 324 patients

The Z0011 trial has fundamentally changed axillary management in breast cancer patients. However, some important questions remain, like the role of extracapsular nodal extension (ENE) in positive sentinel nodes and the need for further axillary treatment. In this retrospective cohort study, we reviewed and analyzed data from 342 clinically node negative (cN0) breast cancer patients with a positive sentinel node and subsequent axillary lymph node dissection (ALND) from the BRENDA data base. The 104 (30.4%) ENE positive patients had a significantly higher proportion of ≥3 positive axillary lymph nodes (65.0%) compared to ENE negative patients with a positive sentinel node (21.4%). Likewise, ENE positive patients had significantly more often lymph node metastasis size >2mm (96.2%) than ENE negative patients (72.7%). T1 status was observed significantly more often in ENE negative patients (53.2%) than in ENE positive patients (24.0%). While ENE was linked to worse overall survival in univariate analysis, this effect disappeared when adjusting for nodal status, age, and comorbidities in multivariate analysis. ENE of the sentinel node is an important predictor for nonsentinel lymph node involvement. We suggest that ENE influences survival only via a higher number of positive nodes - one of the most predictive parameters for survival outcome in breast cancer.

PD51-10 SURVIVAL AFTER RADICAL PROSTATECTOMY IN PATIENTS WITH PSA PERSISTENCE: THE IMPACT OF COMPETING CAUSES OF MORTALITY

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy VI1 Apr 2017PD51-10 SURVIVAL AFTER RADICAL PROSTATECTOMY IN PATIENTS WITH PSA PERSISTENCE: THE IMPACT OF COMPETING CAUSES OF MORTALITY Giorgio Gandaglia, William Parker, Nicola Fossati, Paolo Dell'Oglio, Armando Stabile, Carlo Andrea Bravi, Luigi Nocera, Francesco Pellegrino, Emanuele Zaffuto, Nazareno Suardi, Francesco Montorsi, R. Jeffrey Karnes, Stephen Boorjian, and Alberto Briganti Giorgio GandagliaGiorgio Gandaglia More articles by this author , William ParkerWilliam Parker More articles by this author , Nicola FossatiNicola Fossati More articles by this author , Paolo Dell'OglioPaolo Dell'Oglio More articles by this author , Armando StabileArmando Stabile More articles by this author , Carlo Andrea BraviCarlo Andrea Bravi More articles by this author , Luigi NoceraLuigi Nocera More articles by this author , Francesco PellegrinoFrancesco Pellegrino More articles by this author , Emanuele ZaffutoEmanuele Zaffuto More articles by this author , Nazareno SuardiNazareno Suardi More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , R. Jeffrey KarnesR. Jeffrey Karnes More articles by this author , Stephen BoorjianStephen Boorjian More articles by this author , and Alberto BrigantiAlberto Briganti More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2210AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We aimed to assess the risk of cancer-specific mortality (CSM) in patients with PSA persistence after radical prostatectomy (RP) after accounting for other-cause mortality (OCM). We hypothesized that a non-negligible proportion of patients is at risk of dying from other causes and would not benefit from additional cancer therapies. METHODS We included 829 patients with localized PCa undergoing RP at two referral centers between 1994 and 2014. All patients had PSA persistence after RP defined as a PSA ≥0.1 ng/ml at 8 weeks after surgery. A graphical illustration of the 10-year CSM and OCM rates was generated using competing-risks Poisson regression analyses. Patients were stratified according to age (<65 vs. ≥65 years) and according to their probability of dying from PCa at 10-years (stratified as <10% vs. 10-30% vs. >30%), which was developed from a Cox regression model based on pathologic characteristics and first PSA after surgery. For each strata, survival estimates were calculated. Competing-risks regression models were used to test the effect of age and disease characteristics on CSM after accounting for OCM. RESULTS Overall, 223 (26.9%), 331 (39.9%), and 275 (33.2%) patients had pathologic Gleason score ≤6, 7, and ≥8, and 400 (48.3%), 215 (25.9%), 214 (25.8%), and 172 (20.7%) patients had pT2, pT3a, pT3b/4, and pN1 disease. The median first PSA after surgery was 0.33 ng/ml. Median follow-up was 107 months, during which time 90 and 136 patients died from PCa and from OCM. The 10-year CSM and OCM rates were 12.6% and 11.9%. When considering men with a risk of dying from PCa <10%, the 10-year rate of OCM was higher as compared to the CSM rate (8 vs. 1.6%), regardless of age. The proportion of patients who died from OCM at 10-year was 4.2% in men <65 years with a probability of dying from PCa >30% vs. 18.2% in patients ≥65 years with a probability of CSM between 10 and 30%. In men with a calculated risk of dying from PCa >30% the 10-year CSM rates were 43.7 vs. 34.1% for those aged <65 vs. ≥65 years old. At multivariable regression analyses, the number of positive nodes, first PSA after surgery, and pathologic Gleason score 8-10 (all p<0.001) were associated with the risk of CSM after accounting for the risk of dying from other causes. CONCLUSIONS Up to 20% of men with PSA persistence after RP will ultimately die from other causes. Conversely, patients with Gleason score 8-10, higher PSA after surgery, and a higher number of positive nodes are at increased risk of CSM. These patients might benefit from additional cancer therapies, while men less likely to die from PCa may be spared such treatments. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e987-e988 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Giorgio Gandaglia More articles by this author William Parker More articles by this author Nicola Fossati More articles by this author Paolo Dell'Oglio More articles by this author Armando Stabile More articles by this author Carlo Andrea Bravi More articles by this author Luigi Nocera More articles by this author Francesco Pellegrino More articles by this author Emanuele Zaffuto More articles by this author Nazareno Suardi More articles by this author Francesco Montorsi More articles by this author R. Jeffrey Karnes More articles by this author Stephen Boorjian More articles by this author Alberto Briganti More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP57-20 PATTERNS OF CLINICAL RECURRENCE AND PREDICTORS OF SYSTEMIC PROGRESSION OF PROSTATE CANCER PATIENTS WITH PSA PERSISTENCE AFTER RADICAL PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy III1 Apr 2016MP57-20 PATTERNS OF CLINICAL RECURRENCE AND PREDICTORS OF SYSTEMIC PROGRESSION OF PROSTATE CANCER PATIENTS WITH PSA PERSISTENCE AFTER RADICAL PROSTATECTOMY Giorgio Gandaglia, Nicola Fossati, Paolo Dell'Oglio, Rocco Damiano, Marco Bianchi, Marta Picozzi, Elena Farina, Vito Cucchiara, Roberto Bertini, Federico Dehò, Francesco Montorsi, and Alberto Briganti Giorgio GandagliaGiorgio Gandaglia More articles by this author , Nicola FossatiNicola Fossati More articles by this author , Paolo Dell'OglioPaolo Dell'Oglio More articles by this author , Rocco DamianoRocco Damiano More articles by this author , Marco BianchiMarco Bianchi More articles by this author , Marta PicozziMarta Picozzi More articles by this author , Elena FarinaElena Farina More articles by this author , Vito CucchiaraVito Cucchiara More articles by this author , Roberto BertiniRoberto Bertini More articles by this author , Federico DehòFederico Dehò More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , and Alberto BrigantiAlberto Briganti More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.674AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Previous studies demonstrated that Prostate Cancer (PCa) patients who experience PSA persistence after radical prostatectomy (RP) are at increased risk of clinical progression and death. We hypothesized that the outcomes of patients with PSA persistence after RP are heterogeneous and that not all patients would ultimately experience adverse outcomes METHODS A total of 170 patients with clinically localized PCa undergoing radical prostatectomy (RP) at a single referral tertiary center between 1994 and 2014 were identified. All patients included in the study had a PSA≥0.1 ng/ml 6 weeks after surgery. Biochemical recurrence (BCR) was defined as two consecutive PSA raises≥0.2ng/ml. Clinical recurrence (CR) was defined as positive imaging during follow-up after the onset of BCR. Patients were stratified according to the site of CR in those with local (prostate bed and/or pelvic lymph nodes relapse) and systemic recurrence (retroperitoneal lymph nodes and/or skeletal and/or visceral relapse). Kaplan-Meier analyses assessed time to BCR and CR. Multivariable Cox regression analyses assessed the predictors of systemic recurrence RESULTS Median age at surgery was 64.8 years. Overall, 22 (12.9%), 64 (37.6%), and 84 (49.4%) patients had pathologic Gleason score ≤6, 7, and ≥8, respectively. Overall, 88 (51.8%) patients had positive surgical margins and 48 (28.2%), 39 (22.9%), 83 (48.8%), and 96 (56.5%) patients had pT2, pT3a, pT3b/4, and pN1 disease, respectively. The median number of positive nodes was 3. Median follow-up was 63 months. Overall, 110 and 41 patients experienced BCR and CR, respectively. Among patients experiencing CR, 13 (31.7%) vs. 28 (68.3%) had local vs. systemic recurrence. Overall, the 5-year BCR- and CR-free survival rates were 30.3% and 60.2%. At multivariable analyses, lymph node invasion (Hazard Ratio [HR]: 17.6; 95% Confidence Interval [CI]: 1.88-50.6; P=0.01) and the number of positive nodes (HR: 1.04; 95% CI: 1.00-1.05; P=0.03) represented the only independent predictors of experiencing systemic recurrence CONCLUSIONS The oncologic outcomes of patients with PSA persistence after surgery are not invariably poor. At 5-year follow-up, more than 60% of them are free from clinical recurrence. Patients with node-positive disease and with a higher number of positive nodes are at increased risk of experiencing systemic recurrence. These men should receive additional cancer therapies in a timely fashion © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e760-e761 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Giorgio Gandaglia More articles by this author Nicola Fossati More articles by this author Paolo Dell'Oglio More articles by this author Rocco Damiano More articles by this author Marco Bianchi More articles by this author Marta Picozzi More articles by this author Elena Farina More articles by this author Vito Cucchiara More articles by this author Roberto Bertini More articles by this author Federico Dehò More articles by this author Francesco Montorsi More articles by this author Alberto Briganti More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Clinical and Pathological Characteristics of Mucinous Colorectal Adenocarcinoma: A Comparative Study

Background Mucinous adenocarcinoma accounts for approximately 5% - 15% of all colorectal cancers. Objectives The aim of this study was to investigate the clinicopathological characteristics of patients with mucinous colorectal adenocarcinoma. Patients and Methods This retrospective study was carried out by reviewing the medical records of 70 mucinous colorectal cancer (MCC) patients who were diagnosed and treated at a tertiary academic hospital between 2005 and 2010. For the comparative analysis, 491 patients with non-mucinous colorectal cancer (NMCC) were included. Results Of 561 patients with colorectal adenocarcinoma, 70 patients (12.5%) had the mucinous type. There were 42 (60%) men and 28 (40%) women, with a median age of 55 years old (range 24 - 81 years) included in the study. We did not find any differences regarding the patients’ mean age (P = 0.408) and male/female ratio (P = 0.700) between the MCC and NMCC; however, there was a predilection for the right colon and sigmoid colon in the MCC, when compared to the NMCC (P = 0.012). In addition, the MCC tended to have a larger tumor size (P = 0.004), higher histological grade (P < 0.001), higher node stage (P < 0.001), higher number of dissected nodes (P = 0.013), higher number of positive nodes (P < 0.001), and a higher rate of perineural invasion (P = 0.013) compared to the NMCC. Conclusions This study indicates that most clinicopathological characteristics of MCC are different from those of NMCC. In addition, there was an association between the mucinous subtype and adverse pathological features in the patients with colorectal cancer.

Determinants of long-term survival of patients with locally advanced prostate cancer: the role of extensive pelvic lymph node dissection.

The therapeutic effect of pelvic lymph node dissection (PLND) during radical prostatectomy (RP) due to prostate cancer (PCa) is still under debate. We aimed at assessing the impact of more extensive PLND on cancer-specific mortality (CSM) in patients treated with surgery for locally advanced PCa. We examined data of 1586 pT3-T4 PCa patients treated with RP and extended PLND between 1987 and 2012 at a tertiary referral care center. Univariable and multivariable Cox regression analyses tested the relationship between the number of nodes removed and CSM rate, after adjusting for potential confounders. Survival estimates were based on the multivariable models. The average number of nodes removed was 19 (median: 17; interquartile range: 11-23). Mean and median follow-up were 80 and 72 months, respectively. At multivariable analyses, Gleason score 8-10 (hazard ratio (HR): 2.5) and a higher number of positive nodes (HR: 1.06) were independently associated with higher CSM rate (all P<0.05). Conversely, higher number of removed LNs (HR: 0.94) and adjuvant radiotherapy (HR: 0.54) were independent predictors of lower CSM rates (all P⩽0.03). In pT3-T4 PCa patients, removal of a higher number of LNs during RP was associated with higher cancer-specific survival rates. This supports the role of more extensive PLNDs in this patient group. Further prospective studies are needed to validate our findings.

Predictors of recurrence free survival for patients with stage II and III colon cancer.

BackgroundThe aim of this study was to evaluate clinico-pathologic specific predictors of recurrence for stage II/III disease. Improving recurrence prediction for resected stage II/III colon cancer patients could alter surveillance strategies, providing opportunities for more informed use of chemotherapy for high risk individuals.Methods871 stage II and 265 stage III patients with colon cancers were included. Features studied included surgery date, age, gender, chemotherapy, tumor location, number of positive lymph nodes, tumor differentiation, and lymphovascular and perineural invasion. Time to recurrence was evaluated, using Cox’s proportional hazards models. The predictive ability of the multivariable models was evaluated using the concordance (c) index.ResultsFor stage II cancer patients, estimated recurrence-free survival rates at one, three, five, and seven years following surgery were 98%, 92%, 90%, and 89%. Only T stage was significantly associated with recurrence. Estimated recurrence-free survival rates for stage III patients at one, three, five, and seven years following surgery were 94%, 78%, 70%, and 66%. Higher recurrence rates were seen in patients who didn’t receive chemotherapy (p = 0.023), with a higher number of positive nodes (p < 0.001). The c-index for the stage II model was 0.55 and 0.68 for stage III.ConclusionsCurrent clinic-pathologic information is inadequate for prediction of colon cancer recurrence after resection for stage II and IIII patients. Identification and clinical use of molecular markers to identify the earlier stage II and III colon cancer patients at elevated risk of recurrence are needed to improve prognostication of early stage colon cancers.

Survival of patients with operable breast cancer (Stages I-III) at a Brazilian public hospital - a closer look into cause-specific mortality

BackgroundBreast cancer incidence is increasing. The survival rate varies and is longer in high-income countries. In Brazil, lower-income populations rely on the Unified Public Health System (Sistema Único de Saude, SUS) for breast cancer care. The goal of our study is to evaluate the survival of patients with operable breast cancer stages I-III at a Brazilian public hospital that treats mostly patients from the SUS.MethodsA cohort study of patients who underwent surgery for breast cancer treatment at the Clinical Hospital of the Federal University of Minas Gerais from 2001 to 2008 was performed, with a population of 897 cases. Information on tumor pathology and staging, as well as patients’ age and type of health coverage (SUS or private system) was collected. A probabilistic record linkage was performed with the database of the Mortality Information System to identify patients who died by December 31th, 2011. The basic cause of death was retrieved, and breast cancer-specific survival rates were estimated with the Kaplan-Meier method. The Cox proportional hazards model was used for univariate and multivariate analysis of factors related to survival.ResultsA total of 282 deaths occurred during the study’s period, 228 of them due to breast cancer. Five-year breast cancer-specific survival rates were 95.5% for stage I, 85.1% for stage II and 62.1% for stage III disease. Patients from the SUS had higher stages at diagnosis (42% was in stage III, and from the private system only 17.6% was in this stage), and in the univariate but not multivariate analysis, being treated by the SUS was associated with shorter survival (hazard ratio, HR = 2.22, 95% CI 1.24-3.98). In the multivariate analysis, larger tumor size, higher histologic grade, higher number of positive nodes and age older than 70 years were associated with a shorter breast cancer-specific survival.ConclusionsFive-year breast cancer survival was comparable to other Brazilian cohorts. Patients treated by the SUS, rather than by the private system, had shorter survival times, mostly due to higher initial stage of the disease.

Thymidine Phosphorylase Gene Expression in Stage III Colorectal Cancer

BackgroundThe thymidine phosphorylase (TP) enzyme has several tumor-promoting functions. The aim of this study was to explore TP gene expression in relation to clinical and histopathological data obtained from patients with stage III colorectal cancer.Methods and resultsTP gene expression was analyzed by real-time quantitative PCR in tumor and mucosa samples from 254 patients. TP gene expression in tumors correlated with lymph node staging, with higher expression relating to a higher number of positive nodes and a worse N-stage. Higher TP expression was also associated with a worse histological tumor grade. Patients with rectal cancer had significantly higher TP expression in mucosa and tumors compared with patients having colon cancer.ConclusionHigher intratumoral TP expression appears to be related to a worse N stage, and thus, with a worse prognosis. TP gene expression measured in a preoperative biopsy could be of interest in preoperative staging.

Stromal Caveolin-1 Expression in Breast Carcinoma. Correlation with Early Tumor Recurrence and Clinical Outcome

Caveolin- (cav-1) has been linked to tumor progression and clinical outcome in breast cancer, but its role as a prognostic marker is still unclear. We evaluated stromal and tumor caveolin-1 expression in 91 breast carcinomas, and assessed the association between their expression and clinicopathologic variables as well as patient outcome and early tumor recurrence. Absence of stromal caveolin-1 expression was detected in 18.7% of cases, while 25.3% of cases revealed tumor epithelial caveolin-1 expression. Combined stromal and tumor caveolin-1 immunopositivity was seen in 24.2% of cases. Absence of stromal cav-1 associated with larger tumor size, higher grade, higher nodal stage, higher number of positive nodes, higher TNM stage, positive HER2 status, higher recurrence rate, and shorter mean progression free survival (PFS). Stromal cav-1 status was a significant predictor of PFS in ER+, PR +, and HER2 + tumors. In tamoxifen-treated patients, absence of stromal Cav-1 was a significant predictor of poor clinical outcome, suggestive of tamoxifen resistance. Conversely, tumor epithelial and combined caveolin-1 expression, didnot associate with patient outcome. In multivariate analysis, only TNM stage independently associated with survival. Loss of stromal caveolin-1 is a novel breast cancer biomarker that can predict early tumor recurrence, short PFS, and tamoxifen- resistance. Thus, its use as a predictive biomarker, especially in lower grade, lower stage, ER+, PR+, HER2+, and tamoxifen treated patients may allow for early interventions with more aggressive therapies. Thus, stromal marker expression and epithelial-stromal cross talk may be critical for tumor progression and metastasis.

The number of lymph nodes with metastatic disease portends for a poorer prognosis in women with stage IIIC-IV endometrioid uterine cancer

5039 Background: To determine the prognosis of women with IIIC-IV endometrioid uterine cancer based on the number lymph nodes with metastatic disease Methods: Demographic and clinico-pathologic information were obtained from the Surveillance, Epidemiology and End Results Program from 1988–2001 and analyzed using Kaplan-Meier methods and Cox proportional hazards regression. Results: Of the 1,222 women diagnosed with stage IIIC-IV endometrioid uterine cancer with nodal disease, the median age was 64 (range: 28–93). All patients underwent surgical staging including a lymph node assessment and were found to have nodal metastases. 639 (52.3%) had stage IIIC, 24 (2.0%) IVA, and 559 (45.7%) IVB disease. The study cohort was divided in three subgroups based on the number of positive nodal metastases: 1, 2–5, and &gt;5. The 5-year overall disease-specific survivals of women with 1, 2–5, and &gt;5 positive nodes were 68.1%, 55.1% and 46.4%, respectively (p &lt; 0.0001). The increasing number of positive nodes was associated with a worsening survival in stage IIIC (77.1%, 60.9%, 69.1%; p = 0.003) and stage IV (50.9%, 49.8%, 38.9%; p = 0.09) diseases. It appears that the extent of benign nodal resection attenuates the increase in the mortality associated with a higher number of positive nodes (see table ). Women with higher number of positive nodes received significantly less adjuvant radiotherapy at 76.8%, 59.5%, and 56.7% respectively. On multivariate analysis, age, stage, grade, number of positive lymph nodes and extent of lymph node resection were significant independent prognostic factors for survival. However, adjuvant radiation was not an important independent prognostic factor in multivariate analysis. Conclusion: Women with node positive endometrioid uterine cancers have a decreased survival associated with increasing number of positive nodes. Our data suggests that the extent of lymph node resection improves the survival of patients with node-positive uterine cancer. [Table: see text] No significant financial relationships to disclose.

Evaluation of the prognostic and predictive value of p53 and Bcl-2 in breast cancer patients participating in a randomized study with dose-dense sequential adjuvant chemotherapy

To assess the prognostic and predictive significance of p53 and Bcl-2 protein expression in high risk patients with breast cancer treated with dose-dense sequential chemotherapy. From June 1997 until November 2000, 595 patients were randomized to three cycles of epirubicin (E) 110 mg/m2 followed by three cycles of paclitaxel (P) 250 mg/m2 followed by three cycles of 'intensified' CMF (cyclophosphamide 840 mg/m2, methotrexate 47 mg/m2 and fluorouracil 840 mg/m2) or to four cycles of E, followed by four cycles of CMF. p53 and Bcl-2 expression was investigated by immunohistochemistry in 392 and 397 patients respectively. Positive expression of p53 was detected in 104 (26.5%) patients and was significantly associated with negative hormonal status, worse histologic grade, higher incidence of disease relapse and higher rate of death. p53 positive expression was a significant negative predictor of overall survival (OS) (P = 0.002) and disease-free survival (DFS) (P = 0.001). Negative expression of Bcl-2 was detected in 203 (51%) patients and was significantly associated with negative hormonal status. Multivariate analysis revealed that, positive p53 expression, higher number of positive nodes and worse tumor grade were related to significantly poorer OS and DFS. For both treatments, p53 positive expression was a significant negative prognostic factor for OS and DFS while Bcl-2 was not. No predictive ability of p53 status or Bcl-2 status for paclitaxel treatment was evident.

Variability in axillary lymph node dissection for breast cancer.

The axillary nodal status may influence the prognosis and the choice of adjuvant treatment of individual breast cancer patients. The variation in number of reported axillary lymph nodes and its effect on the axillary nodal stage were studied and the implications are discussed. Between 1994 and 1997, a total of 4,806 axillary dissections for invasive breast cancers in 4,715 patients were performed in hospitals in the North-Netherlands. The factors associated with the number of reported nodes and the relation of this number with the nodal status and the number of positive nodes were studied. The number of reported nodes varied significantly between pathology laboratories, the median number of nodes ranged from 9 to 15, respectively. The individual hospitals explained even more variability in the number of nodes than pathology laboratories (range in median number 8-15, P < 0.0001). The number of reported nodes increased gradually during the study period. A decreasing trend was observed with older patient age. A higher number of reported nodes was associated with a markedly increased chance of finding tumor positive nodes, especially more than three nodes. The frequency of node positivity increased from 28% if less than six nodes to 54% if >/=20 nodes were examined, the percentage of tumors with >/=4 positive nodes increased from 4 to 31%. Multivariate analysis confirmed these results. This population-based study showed a large variation in the number of reported lymph nodes between hospitals. A more extensive surgical dissection or histopathological examination of the specimen generally resulted in a higher number of positive nodes. Although the impact of misclassification on adjuvant treatment will have varied, the impact with regard to adjuvant regional radiotherapy may have been considerable.

P(21WAF1/CIP1) expression in breast cancers: associations with p53 and outcome.

p21(WAF1/CIP1) is transcriptionally activated by wt p53 and inhibits G1 associated cyclins, a major mechanism by which p53 inhibits cellular proliferation. Archival breast cancers (798) with a median follow-up of 16.3 years were used to explore the prognostic value of p21 immunohistochemical analyses. p21 immunostaining was detected in the majority (726/798: 91%) of breast cancers as well as adjacent in situ carcinomas (125/170: 74%), hyperplastic lesions (140/349: 40%) and normal breast epithelium adjacent to carcinoma (3/89: 3%). Complete immunonegativity was observed in only 9% of invasive cancers and was associated with p53 immunopositivity (p < 0.05). Univariate analysis of all patients showed that p21 negativity was associated with a longer disease specific survival (relative risk (RR) 1.5). Node positive p21- patients also showed a longer disease free and disease specific survival as compared to tumor p21+ patients. In node negative patients, p53 positivity but not p21 alone, was significantly associated with a shortened disease free survival (RR = 1.6). Node negative patients who were p53+ p21-, in particular had the shortest disease free survival compared to other p53, p21 subgroups (i.e., p21 negativity was associated with a worse outcome). Multivariate analysis of lymph node negative patients (n > 300) demonstrated that tumor size and tumor grade were independently predictive of outcome, whereas neither p53 nor p21 were significant. For node positive patients, p21 positivity (p = 0.05), p53 positivity (p = 0.03), a higher number of positive nodes, larger tumor size, steroid receptor negativity, high proliferation rate, and erbB-2 expression were each independently associated with poor outcome. In summary, p21 negativity was inversely correlated with p53 immunopositivity in the majority of cases. p21 negative tumor patients had an improved outcome if they were node positive, whereas p21 status was not significantly associated with survival in node negative patients. This observation may be due to the reported 'uncoupling of S phase and mitosis' associated with a loss of p21 expression which may result in enhanced sensitivity to chemotherapy.