Prognostic Factor For Disease-specific Survival Research Articles

Intrahepatic Cholangiocarcinoma: Clinicopathological Differences Between Peripheral Type and Hilar Type

BackgroundIntrahepatic cholangiocarcinoma (ICC) is categorized as peripheral ICC (PICC) or hilar ICC (HICC). The aims of this study are to clarify clinicopathological differences between PICC and HICC and to determine useful prognostic factors for patients with ICC following aggressive surgical resection. MethodsMedical records of 44 patients with ICC who underwent surgical resection were retrospectively reviewed. Clinicopathological factors were compared between patients with PICC and HICC. Univariate and multivariate models were used to analyze the effect of clinicopathological factors on disease-specific survival. ResultsDisease-specific survival rates for the 44 patients were 76% at 1 year, 60% at 3 years, and 47% at 5 years. Clinicopathological factors did not differ between patients with PICC and HICC except preoperative jaundice (P < 0.001), preoperative biliary drainage (P = 0.001), postoperative complication (P = 0.046), and macroscopic type (P < 0.001). Multivariate analysis revealed that only lymph node status was an independent prognostic factor of disease-specific survival. The 5-year disease-specific survival rates of patients with or without nodal involvement were 23% and 66%, respectively (P = 0.004). ConclusionsClinicopathological characteristics are almost similar between patients with PICC and HICC. Nodal involvement is a potent prognostic factor for patients with ICC.

Prostate cancer in the senior men from rural areas in east district of China: Contemporary management and 5-year outcomes at multi-institutional collaboration

Objective Prostate cancer is an underreported and emerging problem in China. Here we summarize the data for Chinese patients with prostate cancer (PCa), describe available treatment options, and report 5-year outcomes at multiple tertiary care institutions. Patients and methods A series of 1611 patients (mean age 76.51 years) diagnosed with PCa were enrolled. Survival rates for patients were analyzed using the Kaplan–Meier method. Prognostic factors for disease-specific survival were analyzed using the log-rank test and Cox proportional hazards model. Results Seven hundreds and thirty-two patients with a prostate tumor clinical stage of III or IV and 879 with a tumor clinical stage of I or II were diagnosed. The disease-specific survival rates at 1, 3 and 5 years were 94.6%, 81.3% and 72.6%, respectively. Five-year disease-specific survival rates were 99.2% for patients with low clinical stage PCa who underwent radical prostatectomy, 76.5% for those who underwent transurethral resection of the prostate plus hormone therapy, 38% for those who received hormone therapy plus radiation therapy and 29% for those that received hormone therapy alone. Conclusions In keeping with a lack of prostate-specific antigen (PSA)-based screening, Chinese men present later in life and course of their disease, with over 27% men dying of PCa at five years. Debulking of tumors by surgery and radiation therapy for high grade tumor may provide some survival benefit in the senior men but further study is required to validate these findings. It is important of the annual use of PSA test for men over 50 years old to detect the PCa in the early stage in this nation.

Identification of PRDX4 and P4HA2 as Metastasis-Associated Proteins in Oral Cavity Squamous Cell Carcinoma by Comparative Tissue Proteomics of Microdissected Specimens Using iTRAQ Technology

Cervical lymph node metastasis represents the major prognosticator for oral cavity squamous cell carcinoma (OSCC). Here, we used an iTRAQ-based quantitative proteomic approach to identify proteins that are differentially expressed between microdissected primary and metastatic OSCC tumors. The selected candidates were examined in tissue sections via immunohistochemistry, and their roles in OSCC cell function investigated using RNA interference. Seventy-four differentially expressed proteins in nodal metastases, including PRDX4 and P4HA2, were identified. Immunohistochemical analysis revealed significantly higher levels of PRDX4 and P4HA2 in tumor cells than adjacent non-tumor epithelia (P < 0.0001 and P < 0.0001, respectively), and even higher expression in the 31 metastatic tumors of lymph nodes, compared to the corresponding primary tumors (P = 0.060 and P = 0.002, respectively). Overexpression of PRDX4 and P4HA2 was significantly associated with positive pN status (P = 0.048 and P = 0.021, respectively). PRDX4 overexpression was a significant prognostic factor for disease-specific survival in both univariate and multivariate analyses (P = 0.034 and P = 0.032, respectively). Additionally, cell migration and invasiveness were attenuated in OEC-M1 cells upon in vitro knockdown of PRDX4 and P4HA2 with specific interfering RNA. Novel metastasis-related prognostic markers for OSCC could be identified by our approach.

Overexpression of matrix metalloproteinase-7 and -9 in NSCLC tumor and stromal cells: Correlation with a favorable clinical outcome

Background Matrix metalloproteinases (MMPs) are considered important players in angiogenesis and cancer progression. Several drugs developed for targeting MMPs have until now been without clinical efficacy. As both malignant cells and cells of the surrounding stroma contribute to tumor growth, we have explored the impact of MMP-2, -7 and -9 expression in both the tumor and stromal compartment of non-small-cell lung cancers (NSCLC). Patients and methods From 335 unselected stage I to IIIA NSCLC carcinomas, duplicate tumor and tumor-associated stromal cores were collected in tissue microarrays (TMAs). Immunohistochemistry was used to detect the expression of MMP-2, -7 and -9 in tumor and stromal cells. Results In univariate analyses, high tumor cell MMP-7 expression ( P = 0.029) and high stromal MMP-9 expression ( P = 0.001) were positive prognostic factors. In the multivariate analysis, high tumor cell MMP-7 expression (HR 1.58, CI 1.08–2.32, P = 0.020) and high stromal MMP-9 expression (HR 1.92, CI 1.25–2.96, P = 0.003) were independent positive prognostic factors for disease-specific survival. Conclusion High levels of MMP-7 in tumor cells and high levels of MMP-9 in tumor associated stroma were independent positive prognostic factors in NSCLC patients.

Impact of intratumoral thymidylate synthase expression on prognosis after surgical resection for ampullary carcinoma

This study evaluated possible prognostic value of expression level of intratumoral thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and orotate phosphoribosyltransferase (OPRT) in patients with resected ampullary carcinoma. Immunohistochemical staining evaluated intratumoral TS, DPD, and OPRT expression in 52 surgical specimens of patients with ampullary carcinoma. Relationships between clinicopathological factors including intratumoral TS, DPD, or OPRT expressions and survival was evaluated by univariate and multivariate analysis. High intratumoral DPD, OPRT, and TS expressions were found in 19 (37%), 30 (58%), and 23 (44%) of cases, respectively. Patients with high TS expression had more advanced-stage disease than those with low TS expression. Univariate analysis revealed that gender, perineural invasion, lymph node status, UICC pT factor, UICC stage, OPRT expression, and TS expression correlated significantly (P < 0.05) with disease-specific survival. Only perineural invasion (P = 0.043) and TS expression (P = 0.019) were independent prognostic factors of disease-specific survival by multivariate survival analysis. Five-year disease-specific survival rates of patients with high and low intratumoral TS expression were 47% and 91%, respectively. Intratumoral TS expression level may be a potent predictor of prognosis after surgical resection for ampullary carcinoma.

Defining Cure for Esophageal Cancer: Analysis of Actual 5-Year Survivors Following Esophagectomy

Esophagectomy is the mainstay of curative treatment for localized esophageal cancer. However, what constitutes cure is not well defined. This study was undertaken to characterize actual 5-year survivors following esophagectomy and to determine prognostic factors for disease-specific survival (DSS) from 60months. Between 1987 and 2004, 398 consecutive patients underwent esophagectomy and had potential for 5years follow-up. Clinicopathological factors associated with DSS from 5years onward were analyzed. Median DSS was 25months. Neoadjuvant therapy was administered to 159 of 398 (40%). There were 114 of 398 (29%) actual 5-year survivors. On multivariate analysis, 5-year survivors were significantly more likely to have lower T classification, N classification, and R0 resections compared with patients who died less than 5years after surgery. There were 66 of 398 patients (17%) with positive margins, and 6 of these were 5-year survivors. Of the 114 5-year survivors, 17 (15%) subsequently died of esophageal cancer. Prognostic factors for DSS after surviving 5years were age and T classification for patients treated with neoadjuvant therapy and surgery alone, respectively. Powerful prognostic factors from time of treatment, including nodal status, were no longer prognostic factors after surviving to 5years. No single clinicopathological variable negated survival to 5years. Prognostication once surviving 5years is difficult. The majority of 5-year survivors can be considered cured of esophageal cancer.

Clinical Significance of Epidermal Growth Factor Receptors in Non-small Cell Lung Cancer and a Prognostic Role for HER2 Gene Copy Number in Female Patients

To compare the efficacy of silver in situ hybridization (SISH) and immunohistochemistry (IHC) in detecting HER2 alterations and to investigate the prevalence and prognostic significance of Erb family members in non-small cell lung cancer (NSCLC). Stage I to IIIA tumors from 335 patients with NSCLC were immunohistochemically tested for protein expression of all Erb family members. Membranous HER2 expression was compared with its gene copy number by SISH in paraffin-embedded, formalin-fixed material. Correlations were made with clinicopathological variables. Synchronous high immunohistochemical expression of all Erb family members was seen in 8% of tumor samples. There was a significant correlation between the HER2 gene copy number and HER2 protein expression (p = 0.003). High nuclear HER3 expression correlated significantly with high HER2 gene copy numbers (p = 0.015). In univariate analyses, high HER2 gene copy number was a highly significant negative prognostic indicator for disease-specific survival in women (p = 0.005), whereas it did not show prognostic influence in men (p = 0.9). Neither polysomy of chromosome 17 nor the IHC expression of Erb family member proteins as singles or pairs correlated significantly with survival. In the multivariate analysis, high HER2 gene copy number in tumor epithelial cells (p = 0.03) was an independent prognostic factor for disease-specific survival in female patients. IHC does not consistently identify patients likely to have a poor prognosis, whereas SISH provides superior prognostic information for female patients with NSCLC. High HER2 gene copy number in tumor epithelial cells is an independent predictor of inferior survival in female patients with primary NSCLC.

Disease-specific Survival in Patients with Renal Cell Carcinoma: An Audit of a Large Series from Korea

To evaluate the question of whether or not young age is an independent prognostic factor for disease-specific survival in Korean patients with renal cell carcinoma. A total of 785 patients with an age range of 22-84 years (median, 56) were included in the study. Patients were categorized according to age; 40 years or less (n = 93), 41-60 years (n = 416) and older than 60 years (n = 276). Patients 40 years or less at diagnosis differed significantly from older patients for the following parameters: smaller tumour diameter (P = 0.001), less advanced stage (P = 0.002), lower Fuhrman nuclear grade (P = 0.017) and fewer clear cell carcinomas (P < 0.001). Five-year disease-specific survival rate in patients 40 years or younger was also higher than that of older patients (92.7% versus 86.0% versus 69.2%; P < 0.001). When subgroup analysis was performed, only in patients with tumour diameter 4.1-7.0 cm (P = 0.018), pT1-pT2,N0,M0 (P = 0.001) or clear cell type carcinoma (P < 0.001), disease-specific survival probability for patients 40 years or younger was higher than that of older patients. When the Cox proportional hazards model was applied, age at diagnosis was not an independent prognostic predictor of disease-specific survival. Tumours found in young adults show more favourable histological features than those found in older adults. However, according to results from multivariate analysis, young patients do not have higher disease-specific survival rate after adjusting for clinical and pathological variables.

Expression of parvin-β is a prognostic factor for patients with urothelial cell carcinoma of the upper urinary tract

Background:Parvin-β (ParvB), a potential tumour suppressor gene, is a focal adhesion protein. We evaluated the role of ParvB in the upper urinary tract urothelial cell carcinoma (UUT-UC).Methods:ParvB mRNA and proteins levels in UUT-UC tissue were investigated by quantitative real-time polymerase chain reaction and western blot analysis, respectively. In addition, the expression of ParvB in tissues from patients with UUT-UC at different stages was evaluated by immunohistochemistry. Furthermore, biological functions of ParvB in urothelial cancer cells were investigated using a doxycycline-inducible overexpression system and siRNA.Results:Western blot and mRNA analysis showed downregulation of ParvB expression in frozen UUT-UC tissue. Immunohistochemistry revealed high staining intensity of ParvB in normal urothelium, which decreased markedly at advanced stages of UUT-UC (P=0.0000). Moreover, ParvB was an independent prognostic indicator for disease-specific survival of patients with UUT-UC. Functional assays indicated that overexpression of ParvB in an urothelial cancer cell line resulted in decreased cell growth rate and ability to migrate. In contrast, knockdown of ParvB expression increased cell migration ability.Conclusions:Downregulation of ParvB expression significantly increased urothelial cancer cell growth and migration. Downexpression of ParvB level in UUT-UC correlated with tumour stage, and was an independent unfavourable prognostic factor for disease-specific survival of patients with UUT-UC.

The prognostic value of intraepithelial and stromal CD3‐, CD117‐ and CD138‐positive cells in non‐small cell lung carcinoma

The major value of prognostic markers in potentially curable non-small cell lung carcinoma (NSCLC) should be to guide therapy after surgical treatment. Although tumor-infiltrating T lymphocytes and plasma cells have been documented in NSCLC, a clear association with clinical outcome, especially for the stromal component, has not been well established. The aim of this study was to elucidate the prognostic significance of these cells/markers in the epithelial and stromal compartments of NSCLC. Tissue microarrays from 335 resected, stage I-IIIA, NSCLC were constructed by duplicate cores from viable neoplastic epithelial and stromal areas. Immunohistochemistry was used to evaluate the infiltration of CD3(+), CD117(+) as well as CD138(+) cells in epithelial and stromal areas. In univariate analyses, increasing numbers of stromal CD3(+) (p = 0.001) and epithelial CD3(+) cells (p = 0.004) correlated significantly with an improved disease-specific survival. No such relation was noted with CD3(+) or CD117(+) cells. In the multivariate analysis, stromal CD3(+) cells was an independent prognostic factor for disease-specific survival (HR 1.925, CI 1.21-3.04, p = 0.005). Increased presence of the pan T-cell marker, CD3, which is an independent factor, correlates with improved clinical outcome in NSCLC. This prognostic impact of T cells is clearer in the tumor stroma. Neither plasma cells nor mast cells were prognostic indicators in our cohort.

419 THE IMPACT OF SERUM CYFRA 21-1 ON THE PROGNOSIS OF PATIENTS WITH UPPER URINARY TRACT UROTHELIAL CARCINOMA

You have accessJournal of UrologyUrothelial Cancer: Upper Tract Tumors1 Apr 2010419 THE IMPACT OF SERUM CYFRA 21-1 ON THE PROGNOSIS OF PATIENTS WITH UPPER URINARY TRACT UROTHELIAL CARCINOMA Taisuke Suyama, Shigeki Kanbe, Koichi Nakajima, Hiroshi Hara, Koichi Nagao, and Nobuhisa Ishii Taisuke SuyamaTaisuke Suyama Ota-ku, Tokyo, Japan More articles by this author , Shigeki KanbeShigeki Kanbe Ota-ku, Tokyo, Japan More articles by this author , Koichi NakajimaKoichi Nakajima Tokyo, Japan More articles by this author , Hiroshi HaraHiroshi Hara Tokyo, Japan More articles by this author , Koichi NagaoKoichi Nagao Tokyo, Japan More articles by this author , and Nobuhisa IshiiNobuhisa Ishii Tokyo, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.489AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Although upper urinary tract urothelial carcinoma accounts for only approximately 5% to 7% of urothelial malignancies, its incidence has been increasing in the last 2 decades in the USA. In general, the prognosis for upper urinary tract urothelial carcinoma is worse than that for bladder tumors. Thus, specific prognostic indicators are needed to enable selection of optimal therapies. Previous reports show that pathological T stage, pathological grade, tumor location, lymph node involvement (LNI), lymphovascular invasion (LVI) and surgical procedure are prognostic factors for upper urinary tract urothelial carcinoma. However, all of these are postoperative factors. And to our knowledge, previous report shows that preoperative serum C-reactive protein (CRP) is a biomarker that can predict prognosis in patients with upper urinary tract urothelial carcinoma treated surgically. In the present study we examined the prognostic significance of serum CYFRA 21-1 status in patients with upper urinary tract urothelial carcinoma. METHODS We retrospectively reviewed the clinical records of 61 patients with upper urinary tract urothelial carcinoma. A serum CYFRA 21-1 level less than 3.5 ng/mL is considered normal. Actuarial survival curves were calculated using the Kaplan–Meier method. Differences between survival curves were then evaluated using the log-rank test. Multivariate analysis was performed using a Cox proportional-hazards model. RESULTS During a median follow-up of 29 months (range, 2-234 months), 30 patients (49.1%) died of the disease. Serum CYFRA 21-1 level was not elevated in 33 of the 61 patients (54.1%). The disease-specific survival rate in patients with a high serum CYFRA 21-1 level was significantly lower than in those without a high serum CYFRA 21-1 level (p<0.001). Multivariate analysis revealed that clinical and/or pathological N stage▫@and serum CYFRA 21-1 level were significant prognostic factor for disease-specific survival. CONCLUSIONS This study indicated that an elevation of serum CYFRA 21-1 predicts a poor survival in patients with upper urinary tract urothelial carcinoma. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e165 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Taisuke Suyama Ota-ku, Tokyo, Japan More articles by this author Shigeki Kanbe Ota-ku, Tokyo, Japan More articles by this author Koichi Nakajima Tokyo, Japan More articles by this author Hiroshi Hara Tokyo, Japan More articles by this author Koichi Nagao Tokyo, Japan More articles by this author Nobuhisa Ishii Tokyo, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Diagnostic and prognostic utility of PD-1 in B cell lymphomas.

Aims: Programmed death-1 (PD-1) is expressed by germinal center-associated helper T-cells and acts as a negative regulator of the immune system. PD-1 is encountered on tumor cells of angioimmunoblastic T-cell lymphoma and is a postulated diagnostic marker in chronic lymphocytic leukemia (CLL/SLL). Recent data suggest prognostic importance of PD-1 in follicular lymphoma (FL). We assessed the diagnostic potential and the prognostic importance of PD-1 in B-cell lymphomas. Methods: Distribution of PD-1+ lymphocytes in B-cell lymphomas was studied on 403 cases. Correlation with known biologic and clinical key data was performed. Prognostic cut-off scores were determined by receiver operating curve analysis. Results: PD-1+ tumor-infiltrating lymphocytes were numerous in extranodal marginal zone lymphomas and FL. Their amount decreased from FL grade 1 to grade 3 and to FL with transformation to diffuse large B-cell lymphoma. An increased amount of PD-1 tumor-infiltrating lymphocytes above the prognostic cut-off score (> 2.8%) was a positive prognostic factor of disease-specific survival (DSS) in FL-patients. Five percent of the studied 66 CLL/SLL cases showed unequivocal PD-1 positivity of neoplastic cells. Conclusions: Increased number of PD-1+ tumor-infiltrating lymphocytes is associated with significantly improved DSS in FL and may be useful to predict its heterogeneous clinical behavior. PD-1 has probably limited diagnostic value for primary histopathological CLL/SLL diagnostics.

Diagnostic and Prognostic Utility of PD-1 In B Cell Lymphomas

Aims: Programmed death-1 (PD-1) is expressed by germinal center-associated helper T-cells and acts as a negative regulator of the immune system. PD-1 is encountered on tumor cells of angioimmunoblastic T-cell lymphoma and is a postulated diagnostic marker in chronic lymphocytic leukemia (CLL/SLL). Recent data suggest prognostic importance of PD-1 in follicular lymphoma (FL). We assessed the diagnostic potential and the prognostic importance of PD-1 in B-cell lymphomas.Methods: Distribution of PD-1+ lymphocytes in B-cell lymphomas was studied on 403 cases. Correlation with known biologic and clinical key data was performed. Prognostic cut-off scores were determined by receiver operating curve analysis. Results: PD-1+ tumor-infiltrating lymphocytes were numerous in extranodal marginal zone lymphomas and FL. Their amount decreased from FL grade 1 to grade 3 and to FL with transformation to diffuse large B-cell lymphoma. An increased amount of PD-1 tumor-infiltrating lymphocytes above the prognostic cut-off score (&gt; 2.8%) was a positive prognostic factor of disease-specific survival (DSS) in FL-patients. Five percent of the studied 66 CLL/SLL cases showed unequivocal PD-1 positivity of neoplastic cells.Conclusions: Increased number of PD-1+ tumor-infiltrating lymphocytes is associated with significantly improved DSS in FL and may be useful to predict its heterogeneous clinical behavior. PD-1 has probably limited diagnostic value for primary histopathological CLL/SLL diagnostics.

Preoperative Erythrocyte Sedimentation Rate Is an Independent Prognostic Factor in Japanese Patients with Localized Clear Cell Renal Cell Carcinoma

Introduction: Few studies have examined the prognostic significance of common laboratory variables in Japanese patients with localized clear cell renal cell carcinoma (CCRCC). We evaluate the prognostic significance of preoperative laboratory variables in Japanese patients with localized CCRCC. Patients and Methods: The study included 110 Japanese patients who were pathologically confirmed as nonmetastatic CCRCC (pT1–3 N0M0) after radical nephrectomy at our institution. We assessed the clinical (including laboratory measurements) and pathological findings, with the survival rates after surgery. Results: Tumor stage and erythrocyte sedimentation rate (ESR) were identified as significant independent prognostic factors of progression-free survival in multivariate analysis. As for the prognostic factors for disease-specific survival, tumor stage and ESR had prognostic significance both in univariate and multivariate analyses. When the analysis was limited to pT1, multivariate analysis showed that only ESR was an independent prognostic factor for disease-specific survival. Conclusions: Preoperative ESR is an independent prognostic factor in Japanese patients with localized CCRCC, especially in patients with pT1.

The Lymph Node Ratio Is a Powerful Prognostic Factor of Node‐Positive Colon Cancers Undergoing Potentially Curative Surgery

The number of harvested (LNs) and metastatic nodes (LNs+) represents the most significant factor to define postoperative treatment and prognosis in colon cancer. However, its assessment may be inadequate causing an incorrect cancer staging. The lymph node ratio (LNR: the ratio between metastatic and resected nodes) has shown prognostic significance in many tumors; however, its role in colon cancer is not clearly elucidated. This study investigated LNR as a prognostic factor in node-positive colon cancers. A total of 145 consecutive patients with node-positive colon cancer who underwent curative surgery and adjuvant chemotherapy in a single oncologic unit entered this study. LNR ranged from 0.0416 to 0.9; it was clearly lower in pN1 than pN2 patients, and increased as tumor stage worsened. ROC analysis selected 0.1818 as the best LNR cutoff value. Low LNR patients did significantly better than high LNR patients; this difference was not dependent on the number of LNs and stronger than differences observed by grouping patients according to LNs or LNs+. When stratified by low and high LNR value, pN1 and pN2 patients, as well as stage III subgroups were shown to display substantially different outcomes. LNR was an independent prognostic factor for disease-specific survival, and the only covariate related to disease-free survival. LNR was a robust prognostic indicator for node-positive colon cancers undergoing curative surgery. Because this ratio-based staging was demonstrated to reduce stage migration and to aid in identifying high-risk patients, it should be proposed as a standard tool for colon cancer staging.

A nomogram predicting disease-specific survival after nephrectomy for papillary renal cell carcinoma

5091 Background: Whereas multiple nomograms have been developed to assess outcomes of patients with clear cell renal cell carcinoma, a model to assess prognosis of papillary renal cell carcinoma (PRCC) has not yet been developed. After data collection and slide review of a large cohort of patients, the aim of this study was to develop and to internally validate a nomogram for prediction of disease-specific survival for PRCC. Methods: Out of 2,687 patients who underwent surgery for a renal tumor between 1989 and 2008 at two institutions, 258 (10%) were found to have PRCC. H&amp;E slides were reviewed by one uro-pathologist at each institution for papillary sub-type, tumor grade, microvascular invasion, sarcomatoid features, collecting system invasion and presence and extent of tumor necrosis. A nomogram was constructed as a graphical representation of significant variables of disease-specific survival in multivariate Cox proportional hazards regression analysis. The discrimination and calibration of the nomogram were assessed, both utilizing bootstrapping to obtain relatively unbiased estimates. Results: After a median follow-up of 35 months, 49 PRCC-related deaths (19%) had occurred. In univariate analysis, incidental detection, T, N, M stage, grade, microvascular invasion, collecting system invasion, papillary sub-type, sarcomatoid features, and necrosis were all associated with prognosis. Multivariate Cox proportional hazards analysis, however, identified incidental detection, T stage, M stage, microvascular invasion, and necrosis, but not papillary sub-type as independent prognostic factors of disease-specific survival. These variables formed the basis of the nomogram that predicted 5-year disease-specific survival probability. The nomogram predicted well, with a bootstrapped corrected concordance index of 0.93, and showed good calibration. Conclusions: A highly accurate tool utilizing basic clinical and pathological information for predicting disease-specific survival was developed specifically for PRCC. This tool should be helpful for identification of the subset of PRCC patients with aggressive clinical behavior, and may contribute to the ability to individualize postoperative surveillance and therapy. No significant financial relationships to disclose.

Multiple primary tumors in patients with carcinosarcoma of bladder: A coincidence or an etiological association? A study of 221 carcinosarcoma of bladder cases

e16138 Background: Carcinosarcoma of the bladder are rare; As a result, few studies of carcinosarcoma of the bladder have included sufficient number of patients to define their natural history and to determine the factors that impact survival. The objective of this study was to examine the epidemiology, natural history, and prognostic factors that affect the survival for carcinosarcoma of the bladder by using population-based registries. Methods: The Surveillance, Epidemiology, and End Results (SEER) Program database (1973–2004) was used to identify cases of carcinosarcoma of the bladder by tumor site and histology codes. The association between clinical and demographic characteristics and survival of carcinosarcoma of the bladder was examined. Results: A total of 221 cases of histology confirmed carcinosarcoma of the bladder were identified, this account for approximately 0.11% of primary bladder tumors during same period. By using linked population files, we calculated the incidence of carcinosarcoma of the bladder as a rate 0.22 per 100,000 per year, age-adjusted to year 2000 U.S. standard population. Median age of all patients were 75 years (range 41–96). In about 40% of study population, more than one or multiple primary were also indentified. Majority of (212, 95.9 %) patients received cancer directed surgery. For survival analyses, we excluded the cases that were identified at autopsy or on the basis of death certificates only and the patients have more than one primary. Total 132 patients were included in survival analysis. The median overall survival for all cases was 9 months (range 6–12 months). In multivariate analysis, only tumor stage was found to be significant prognostic factors for disease-specific survival. Conclusions: Carcinosarcoma of the bladder are rare tumors that are challenging, the survival is poor even in patients underwent surgical resection. Better therapy is needed to improve patient's outcome. A significant fraction of carcinosarcoma patients are actually affected by multiple primary tumors, the potential association between carcinosarcoma and other neoplasms remain to be investigated. No significant financial relationships to disclose.

HP12 *ACTUAL 5‐YEAR SURVIVORS FOLLOWING OESOPHAGECTOMY AND PREDICTORS OF SURVIVAL

Purpose: Oesophagectomy remains the mainstay of curative treatment for localised oesophageal cancer. Despite this there is a paucity of data reporting actual 5 year survivors following oesophagectomy. This study was undertaken to identify and characterise actual 5 year survivors who underwent oesophagectomy.Methods: A prospectively maintained database identified 526 patients who underwent oesophagectomy from 1987 to 2008. Patients were followed for a minimum of 5 years or until death. Clinico‐pathologic factors associated with 5 year disease‐specific survivorship were analysed. Median follow‐up for all patients was 40 months.Results: Median disease specific survival (DSS) was 32 months. Neoadjuvant therapy was administered to 248/526 (47%). There were 95/526 (18%) actual 5‐year survivors. On multivariate analysis, 5‐year survivors were significantly lower T stage, N stage and less likely to have received blood transfusion compared with patients who died less than 5 years after surgery. There were 76/526 (14%) patients with positive margins and of these 6 patients were 5 year survivors. Amongst 5‐year survivors, 41 (43%) had neoadjuvant therapy. Of the 95 5‐year survivors, 14 (14%) subsequently died of oesophageal cancer. The prognostic factors for DSS after 5 years were dysphagia or odynophagia at presentation. Stage was no longer a prognostic factor after surviving to 5 years.Conclusion: No single clinico‐pathological variable negated survival to 5 years. Prognostication in 5 year survivors is difficult, but odynophagia and dysphagia at presentation are still active as prognostic factors after 5 years. The majority of 5‐year survivors can be considered cured of oesophageal cancer.

Relationship between vascular endothelial growth factor and Notch1 expression and lymphatic metastasis in tongue cancer

To determine the role of angiogenesis in lymph node metastasis and the depth of invasion in early tongue cancer. Retrospective analysis. The study included 51 subjects with tongue cancer. Immunohistochemical staining for vascular endothelial growth factor, Notch1, and Notch3 was performed. Microvessel density was evaluated by counting the number of CD34-stained microvessels in each pathologic specimen. Significant correlations were found between vascular endothelial growth factor and Notch1 expression and cervical lymph node metastasis (P = 0.020 and P < 0.009, respectively), tumor depth of invasion (P = 0.001 and P < 0.001, respectively), and microvessel density indicated by CD34 staining (P = 0.001 and P < 0.001, respectively). Nodal metastasis (P = 0.022), T stage (P = 0.002), and positive VEGF expression (P = 0.044) were statistically significant prognostic factors for disease-specific survival. Vascular endothelial growth factor and Notch1 expression are significantly related to cervical lymph node metastasis and depth of invasion in tongue cancer patients.

Lymphangiogenesis occurs in upper tract urothelial carcinoma and correlates with lymphatic tumour dissemination and poor prognosis

To describe the lymphatic vessel density and to determine the functional and prognostic significance of tumoral lymphatic vessels in upper tract urothelial carcinoma (UTUC). The study included 65 patients who had a radical nephroureterectomy (RNU) for UTUC between 1997 and 2004. All pathological slides were re-evaluated by one reference pathologist and clinical data were reviewed. Lymphatic endothelial cells (LECs) were stained immunohistochemically using D2-40. The lymphatic vessel density (LVD) was described in representative intratumoral (ITLVD), peritumoral (PTLVD) and non-tumoral (NTLVD) areas. Random samples were selected for double-immunostaining with D2-40 and CD-34 (to distinguish blood and lymphatic vessels) and the proliferation marker Ki-67 to detect lymphangiogenesis. The primary outcome measures were disease-specific survival (DSS) and disease recurrence (urothelial and/or distant). The median (interquartile range) PTLVD was 4.0 (3.0-6.3), and significantly higher than that for ITLVD, of 0.3 (0-1.7) (P < 0.001), and NTLVD, of 3 (2.0-3.7) (P < 0.001). Both a higher ITLVD and PTLVD, the presence of lymphovascular invasion (LVI) (each P < 0.001) and a high tumour grade (P = 0.004) were associated with reduced DSS on univariate analysis. A higher PTLVD (P = 0.028) and the presence of LVI (P = 0.020) independently predicted reduced DSS on multivariate analysis. IT and PT lymphatic vessels showed proliferating LECs in all analysed samples. Lymphangiogenesis is present in UTUC, as shown by a significantly increased PTLVD and proliferating LECs. Our findings suggest functional relevance of PT lymphatic vessels during lymphatic tumour spread. PTLVD is a potential novel prognostic factor for DSS in UTUC, and further prospective studies will be needed to determine the effect of its routine evaluation on clinical outcomes of this malignancy.