Adverse Pathologic Factors Research Articles

The prognostic value of preoperative helicobacter pylori infection in resected gastric cancer.

137 Background: Limited data exist on the prognostic implication of pre-operative Helicobacter pylori (H. pylori) infection in gastric adenocarcinoma (GAC). Our aim was to assess the association of H. pyloriwith recurrence and survival in patients undergoing resection of GAC. Methods: All patients who underwent curative intent resection for GAC from 2000 to 2012 at seven academic institutions comprising the US Gastric Cancer Collaborative were included. 30-day mortalities were excluded. Survival analyses were conducted with Kaplan Meier log rank and multivariate Cox regression. Primary endpoints were recurrence-free survival (RFS) and overall survival (OS). Results: Of 965 patients, 559 met inclusion criteria and had documented pre-operative H. pylori testing. 18.6% (n=104) of patients tested positive for H. pylori pre-operatively. Data regarding treatment of H. pylori was not available. H. pylori infection was associated with younger age (62.1 vs 65.1 years; p=0.041), distal tumor location (82.7% vs 71.9%; p=0.033), and receipt of adjuvant radiation therapy (47.0% vs 34.9%; p=0.032). There were no significant differences in ASA class, margin status, Grade, PNI, LVI, or nodal metastases. The distribution of TNM stage I-III was similar between the two groups. H. pylori status was not associated with tumor recurrence. However, pre-operative H. pylori infection was associated with longer OS (84.3 mo vs 44.2 mo; p=0.008). When accounting for differences in age, tumor location, and delivery of radiation therapy, H. pylori infection persisted as a positive prognostic factor for OS (HR 0.60; CI 0.40-0.91; p = 0.016). Conclusions: Patients with and without preoperative H. pylori infection had no significant differences in adverse pathologic factors including positive margin, high grade, lymph node metastases, or advanced TNM stage. Despite similar disease presentation, pre-operative H. pylori infection was independently associated with improved overall survival. Further studies examining the interaction between H. pylori and tumor immunology and genetics are needed to better understand the relationship between H. pylori and survival in gastric cancer.

Long-term oncologic outcomes of postoperative adjuvant versus salvage radiotherapy in prostate cancer: Systemic review and meta-analysis of 5-year and 10-year follow-up data.

PurposeTo evaluate the oncologic outcomes between adjuvant radiotherapy (ART) and salvage radiotherapy (SRT) in patients with locally advanced prostate cancer or with adverse pathologic factors including positive surgical margin and high Gleason score.Materials and MethodsWe searched the literature published from January 2000 until December 2014 at MEDLINE, PubMed, Web of Science, Embase, ProQuest, and Cochrane Library. To be specific, included were studies comparing ART and SRT settings if they followed up oncologic outcomes more than 5 years.ResultsOverall, 3 retrospective, nonrandomized, observational studies, 1 matched control analysis, and 3 prospective randomized controlled studies met our inclusion criteria including a total of 2,380 patients (1,192 ART vs. 1,188 SRT). Higher favorable results were found in ART than in SRT was seen in the 5-year and 10-year biochemical recurrence (BCR)-free survival (risk ratio [RR], 0.61 and 0.70; 95% confidence interval [CI], 0.54-0.69 and 0.63-0.76). ART had a significantly higher 5-year progression-free survival rate than that in SRT (RR, 0.64; 95% CI, 0.51-0.80), but this was not the same for the 10-year progression-free survival rate (RR, 0.88; 95% CI, 0.72-1.08). There was no significant difference for the 5-year and 10-year overall survival rates between ART and SRT (RR, 0.80 and 0.94; 95% CI, 0.59-1.07 and 0.80-1.11).ConclusionsART showed favorable results in BCR-free survival during the 5-year follow-up period. However, the 10-year progression-free survival and overall survival did not show any difference between ART and SRT.

Is it time to abandon the 5-cm margin rule during resection of distal gastric adenocarcinoma? A multi-institution study of the U.S. Gastric Cancer Collaborative.

A proximal margin distance of 5 cm is advocated for resection of gastric adenocarcinoma (GAC). We assessed the prognostic value of proximal margin (PM) distance on survival outcomes after resection of distal GAC. All patients who underwent resection of distal GAC (antrum/body) from 2000 to 2012 at seven institutions of the U.S. Gastric Cancer Collaborative were included. Patients with positive distal margins or macroscopic residual disease were excluded. The prognostic value of PM distance (assessed in 0.5-cm increments) on overall (OS) and recurrence-free survival (RFS) was assessed by Kaplan-Meier and multivariate regression analysis. A total of 465 patients underwent resection of distal GAC. Of these, 435 had R0 resections; 30 patients had a positive PM. 143 patients had stage I, and 322 had stage II-III tumors. Median follow-up was 44 months. Average PM distance was 4.8 cm. Median OS for patients with PM of 3.1-5.0 cm (n = 110) was superior to patients with PM ≤ 3.0 cm (n = 176) (48.1 vs. 29.3 months; p = 0.01), while a margin >5.0 cm (n = 179) offered equivalent survival to PM 3.1-5.0 cm (50.6 months, p = 0.72). The prognostic value of margin distance was stage specific. On multivariate analysis of stage I patients, PM 3.1-5.0 cm remained associated with improved OS [hazard ratio (HR), 0.16; 95 % confidence interval (95 % CI), 0.04-0.60; p = 0.01]. In stage II-III, neither PM 3.1-5.0 cm nor PM > 5.0 cm was significantly associated with OS; OS was dictated by T stage and nodal involvement. The prognostic value of proximal margin distance after resection of distal gastric cancer appears stage specific. In stage I, a 3.1- to 5.0-cm proximal margin is associated with the same improved OS as a > 5.0-cm margin. In stage II-III disease, other adverse pathologic factors more strongly impact survival than proximal margin distance.

Postoperative Radiation Therapy for Submandibular Gland Carcinomas: What Is the Optimal Elective Nodal Irradiation Volume?

To determine the optimal elective nodal irradiation (ENI) volume in patients with submandibular gland carcinoma (SMGC) treated with postoperative radiation therapy (PORT). A retrospective analysis was performed to investigate 53 patients with SMGC treated with surgery and PORT between 2000 and 2013. Pathological neck nodal metastasis was recorded in 19 patients (39%): 4 with pN1 and 15 with pN2b. The regions of ENI were categorized into bilateral each 3 echelons according to anatomically lymphatic drainages: the 1st echelon for Level I-II and tumor bed, the 2nd echelon for Level III, and the 3rd echelon for Level IV-V. The median radiation dose is 66 Gy. Fifteen patients (28%) received ENI to at least bilateral one echelons adjacent to pathologically involved neck levels. Ten patients (19%) received ENI to at least bilateral 2 echelons (i.e., ipsilateral whole neck and contralateral Level I-III), and 7 patients (13%) received ENI to bilateral 3 echelons (i.e., bilateral whole neck). With a median follow-up of 5.0 years, 9 patients developed nodal failures and one with coincident local recurrence. The 5-year locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) were 78.2%, 62.9%, and 58.5%, respectively. Bilateral ENI to at least one adjacent echelons significantly improved LRC for patients with pT3-4 (P = 0.045), pN(+) (P = 0.001), lymphatic invasion (LI) (P = 0.023), and muscle invasion (MI) (P = 0.044) and improved DFS for patients with pN(+) (P = 0.031). For patients with 2 coincident adverse pathological factors including pT3-4, pN(+), LI, MI, nodal extracapsular spreading, pN2b, and level IV-V nodal involvement, bilateral ENI to at least 2 echelons significantly increased LRC (P = 0.025). For patients possessing ≥ 3 coincident aforementioned adverse pathological factors, ENI to bilateral 3 echelons significantly improved the LRC (P = 0.026). In addition, for patients without aforementioned adverse factors, no nodal recurrence was observed even without bilateral ENI (N = 18). Bilateral ENI to adjacent 1, 2, and 3 echelons are warranted for SMGC patients with 1, 2, and ≥ 3 adverse pathological factors, respectively.

Value of intraoperative neck margin analysis during Whipple for pancreatic adenocarcinoma: a multicenter analysis of 1399 patients.

During pancreaticoduodenectomy (PD) for ductal adenocarcinoma, a frozen section (FS) neck margin is typically assessed, and if positive, additional pancreas is removed to achieve an R0 margin. We analyzed the association of this practice with improved overall survival (OS). Patients who underwent PD for pancreatic ductal adenocarcinoma from January 2000 to August 2012 at 8 academic centers were classified by neck margin status as negative (R0) or microscopically positive (R1) on the basis of FS and permanent section (PS). Impact on OS of converting an FS-R1-neck margin to a PS-R0-neck margin by additional resection was assessed. A total of 1399 patients had FS neck margins analyzed. Median OS was 19.7 months. On FS, 152 patients (10.9%) were R1, and an additional 51 patients (3.6%) had false-negative FS-R0 margins. PS-R0-neck was achieved in 1196 patients (85.5%), 131 patients (9.3%) remained PS-R1, and 72 patients (5.1%) were converted from FS-R1-to-PS-R0 by additional resection. Median OS for PS-R0-neck patients was 21.1 months versus 13.7 months for PS-R1-neck patients (P < 0.001) and 11.9 months for FS-R1-to-PS-R0 patients (P < 0.001). Both FS-R1-to-PS-R0 and PS-R1-neck patients had larger tumors (P = 0.001), more perineural invasion (P = 0.02), and more node positivity (P = 0.08) than PS-R0-neck patients. On multivariate analysis controlling for adverse pathologic factors, FS-R1-to-PS-R0 conversion remained associated with significantly worse OS compared with PS-R0-neck patients (hazard ratio: 1.55; P = 0.009). For patients who undergo pancreaticoduodenectomy for pancreatic ductal adenocarcinoma, additional resection to achieve a negative neck margin after positive frozen section is not associated with improved OS.

MP45-06 CHARACTERIZATION OF ANATOMICAL EXTENSION PATTERN OF LOCALIZED PROSTATE CANCER ARISING IN THE PERIPHERAL ZONE

You have accessJournal of UrologyProstate Cancer: Localized III1 Apr 2014MP45-06 CHARACTERIZATION OF ANATOMICAL EXTENSION PATTERN OF LOCALIZED PROSTATE CANCER ARISING IN THE PERIPHERAL ZONE Mototsugu Muramaki, Hideaki Miyake, and Masato Fujisawa Mototsugu MuramakiMototsugu Muramaki More articles by this author , Hideaki MiyakeHideaki Miyake More articles by this author , and Masato FujisawaMasato Fujisawa More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1203AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives Despite the intensive efforts investigating difference in the clinicopathological characteristic between peripheral zone cancer (PZC) and transition zone cancer (TZC), there have been few studies systematically analyzing the extension pattern of each disease within the prostate gland. However, we previously reported that tumors derived from the PZ seem to spread through the PZ and/or across the capsule, but not through the TZ (BJU Int 2004; 93: 57-9); therefore, in this study, we precisely analyzed the radical prostatectomy (RP) specimens obtained from patients diagnosed as having disease arising from the PZ in order to clarify the extension pattern of PZC and to determine its prognostic significance in patients undergoing RP. Methods Of 174 consecutive patients with clinically localized prostate cancer undergoing RP without any neoadjuvant therapies, 128 patients diagnosed as having PZC based on the evaluation of RP specimens were enrolled in this study. Maximum tumor area (MTA) and maximum tumor volume (MTV) in RP specimens were measured using digital planimetry. A circle with an area equal to MTA, in which the central point was the intersection of the longest line of MTA and the line perpendicularly bisecting the first line, was defined as a hypothetical extension area regardless of anatomical structure. The area within this circle that did not overlap MTA was defined as ΔTA. Results There was a significant correlation between MTV and ΔTA/MTA, introduced as a parameter representing the degree of PZC extension along the anatomical shape of the PZ. ΔTA/MTA in patients with MTV larger than 5 ml was significantly greater than that in those with MTV 5 ml or smaller. Furthermore, ΔTA/MTA was significantly associated with several prognostic indicators, including extracapsular extension, surgical margin status and perineural invasion. Multivariate analysis identified ΔTA/MTA in addition to preoperative serum prostate-specific antigen, extracapsular extension and surgical margin status as independent predictors of biochemical recurrence following RP. Conclusions These findings suggest that PZC extends along the anatomical shape of the PZ during the process of extension in the prostate gland, and that the extension pattern of PZC could be closely represented by the ΔTA/MTA value. Despite the need for further studies, ΔTA/MTA, which is significantly associated with certain kinds of adverse pathological factors, could be used as an independent indicator of biochemical outcome in patients undergoing RP. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e461 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Mototsugu Muramaki More articles by this author Hideaki Miyake More articles by this author Masato Fujisawa More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The impact of body mass index on treatment recommendations for patients with intermediate risk prostate cancer.

48 Background: To evaluate the clinical utility of body mass index (BMI) in predicting adverse pathologic outcomes, hence the need for radiation therapy (RT) following radical prostatectomy (RP) for men with organ-confined prostate cancer. Methods: We compared BMI and preoperative risk factors to adverse pathologic risk factors (RP-risk) that dictate the use of RT following RP. Multivariate analysis was used to determine whether BMI provides clinically relevant information in predicting RP-risk for additional RT as well as biochemical outcome. Results: Patients with elevated BMI had higher RP-risk (p=0.002). Specifically, extraprostatic extension, p less than 0.001; positive surgical margins, p=0.005; and a trend towards worse seminal vesicle invasion, p=0.08. Elevated BMI did not correlate with preoperative risk groupings (p=0.38). However, in patients with intermediate-risk disease BMI greater than 29kg/m2 was strongly associated with higher RP-risk (p=0.03) and higher rate of pathologic upgrading of tumors (p&lt;0.004). Intermediate risk patients with BMI greater than 29kg/m2had a two-fold increased risk of requiring RT following RP based on greater than or equal to two adverse pathologic factors (15% vs. 34%). After controlling for known preoperative risk factors, BMI was an independent predictor of RP-risk for additional RT (p=0.006) and biochemical recurrence (p=0.03). Conclusions: BMI of greater than 29kg/m2 is an independent predictor of adverse RP-risk requiring additional RT, particularly in patients with intermediate risk disease. This select group of patients may be best treated with definitive radiation therapy to prevent the additional toxicity from adjuvant or salvage RT following RP. We propose including BMI in clinical decision-making for appropriate treatment recommendation for patients with intermediate risk prostate cancer.

Trends in the use of postprostatectomy therapies for patients with prostate cancer: A Surveillance, Epidemiology, and End Results Medicare analysis

For patients with adverse pathologic factors (positive surgical margins, extracapsular extension, or seminal vesicle invasion) on prostatectomy pathology, the use and timing of postsurgical treatments are controversial. The goal of the current study was to examine patterns of care in patients with a pathologic indication for postprostatectomy radiotherapy (RT) using the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database. A total of 3460 men treated with radical prostatectomy for localized prostate cancer between 2000 and 2006 with at least 1 adverse pathologic factor and at least 3 years of claims data after surgery were included. Medicare claims through December 31, 2009 were examined. Rates of postprostatectomy hormonal therapy, RT, or both were examined. Logistic regression analysis examined potential factors associated with the receipt and timing of RT. Within 3 years after surgery, 1076 patients (31%) received some form of further therapy, including 850 (25%) who received RT. Receipt of RT was < 35% in all subgroups including every year of study. Fewer than one-half of patients who received RT (43%) did so within 6 months of surgery. On multivariate analysis, pathologic T classification and tumor grade were associated with receipt of RT within 6 months or 3 years of surgery, as were younger age, geographic region, and population density. Rates of postprostatectomy RT remain low and the timing of RT has not appreciably changed since the publication of the randomized trials supporting the use of adjuvant RT. The use of hormone therapy is almost as common as RT, despite a relative lack of evidence supporting its use in this setting.

Epidemiology and prognosis of breast cancer in young women.

Breast cancer is the most common malignancy in women with 6.6% of cases diagnosed in young women below the age of 40. Despite variances in risk factors, Age Standardized Incidence Rates of breast cancer in young women vary little between different countries. Review of modifiable risk factors shows that long-term use of oral contraceptives, low body mass index (BMI) and high animal fat diet consumption are associated with increased risk of premenopausal breast cancer. Decreased physical activity and obesity increase risks of breast cancer in postmenopausal women, but data on premenopausal women rather shows that high BMI is associated with decreased risk of breast cancer. Non-modifiable risk factors such as family history and genetic mutations do account for increased risks of breast cancer in premenopausal women. Breast cancer in young women is associated with adverse pathological factors, including high grade tumors, hormone receptor negativity, and HER2 overexpression. This has a significant negative impact on the rate of local recurrence and overall survival. Moreover, younger women often tend to present with breast cancer at a later stage than their older counterparts, which further explains worse outcome. Despite these factors, age per se is still being advocated as an independent role player in the prognosis. This entails more aggressive treatment modalities and the need for closer monitoring and follow-up.

Locoregional Recurrence Following Accelerated Partial Breast Irradiation for Early-Stage Invasive Breast Cancer: Significance of Estrogen Receptor Status and Other Pathological Variables

Understanding risk factors for locoregional recurrence (LRR) after accelerated partial breast irradiation (APBI) can help to guide patient selection for treatment with APBI. Published findings to date have not been consistent. More data are needed as these risk factors continue to be defined. A total of 277 women with early-stage invasive breast cancer underwent lumpectomy and were treated adjuvantly at our institution with APBI using high-dose rate brachytherapy. APBI was delivered using multicatheter interstitial brachytherapy (91%) or single-entry catheter brachytherapy (9%) to a dose of 32-34Gy in 8-10 twice daily fractions. Failure patterns and risk factors for recurrence were analyzed. With a median follow-up of 61months, the 5-year locoregional control rate was 94.4%. Negative estrogen receptor (ER) status was strongly associated with LRR on multivariate analysis (p<0.005). Lobular histology, the presence of an extensive intraductal component, and lymphovascular invasion also were significant but to a lesser degree than ER-negative status. Patients with multiple risk factors were at highest risk for LRR. Age was not significantly associated with increased risk for LRR. The presence of specific pathological features, particularly ER negative status, was associated with increased risk of LRR in this cohort of women treated with APBI. Further investigation is warranted to determine whether patients with adverse pathological risk factors are at higher risk of LRR after APBI than after conventional whole breast irradiation (WBI), as these same features also may place women at risk for LRR after WBI.

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The link between obesity and oncologic outcomes after RP remains ill-defined. Understanding the effect of surgical proficiency and obesity-related changes in tumor biology on prostate cancer outcomes is paramount to explain the suggested association. The unique and difficult challenges of performing RP in obese men implore adherence to strict surgical principles to optimize the cancer cure. Controlling for margin status, tumor burden, and D'Amico risk category, the BMI was not associated with BCR after RP in the present cohort. Numerous series that revealed an association between the BMI and BCR after RP did not control for margin status 1 Magheli A. Rais-Bahrami S. Trock B.J. et al. Impact of body mass index on biochemical recurrence rates after radical prostatectomy: an analysis utilizing propensity score matching. Urology. 2008; 72: 1246-1251 Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar , 2 Bassett W.W. Cooperberg M.R. Sadetsky N. et al. Impact of obesity on prostate cancer recurrence after radical prostatectomy: data from CaPSURE. Urology. 2005; 66: 1060-1065 Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar or other adverse pathologic risk factors, such as tumor volume. 3 Freedland S.J. Grubb K.A. Yiu S.K. et al. Obesity and risk of biochemical progression following radical prostatectomy at a tertiary care referral center. J Urol. 2005; 174: 919-922 Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar Editorial CommentUrologyVol. 81Issue 5PreviewThe presented series evaluates the effect of obesity on adverse pathologic features at prostatectomy and the BCR rates after surgery. This is a topic that has been studied previously, with varying conclusions. An explanation for the observed inconsistencies in the published data could be the multiple factors that can influence the observed outcomes. Two of the factors that must be considered are surgical proficiency and potential obesity-related changes on tumor biology. Full-Text PDF

Differential HER2 expression in resected gastric cancer: Is there prognostic value?

54 Background: For advanced gastric cancer, the ToGA trial established HER2 as an important therapeutic target in the 20% of patients whose tumors exhibited HER2 overexpression or gene amplification. Others have reported that HER2-positive tumors are associated with poor survival in advanced disease. The expression profile and prognostic value of HER2 in resectable gastric cancer are unknown. Methods: 111 pts underwent curative intent resection of gastric adenocarcinoma between 1/00-6/11 and had tissue available for analysis. Immunohistochemistry (IHC) for HER2 was performed on banked tumor specimens and graded by two pathologists blinded to outcomes utilizing ToGA trial criteria. An IHC score of 0+ or 1+ was regarded as negative, 3+ as positive. Fluorescence in-situ hybridization (FISH) for HER2 was performed on equivocal (2+) IHC samples. Primary outcome was differential expression, secondary outcome was overall survival (OS). Results: Median age was 64 years, 54% were male. Median tumor size was 4 cm, 7.2% had a positive margin, 67.6% were poorly differentiated, 23.4% had perineural invasion, 35.1% had lymphovascular invasion, and 61.3% had nodal metastases. 24 patients had stage I disease (21.6%), 32 stage II (28.8%), and 55 stage III (49.6%). Mean follow-up was 28.9 months, median OS was 27.2 months. HER2 expression by IHC was negative in 61 (55%), equivocal in 37 (33.3%), and positive in 13 (11.7%). Of the 37 equivocal cases, FISH was positive in 8, for a total of 21 HER2-positive cases (18.9%) and 90 HER2-negative cases (81.1%). HER2 status did not correlate with T or N stage, tumor size or location, tumor grade, or perineural or lymphovascular invasion. HER2 status was not associated with OS (p=0.36). Conclusions: Resectable gastric cancer exhibits differential expression of HER2, similar to that of advanced disease. Despite reports suggesting HER2 positive status is associated with aggressive disease and worse outcomes in the advanced setting, HER2 status is not associated with adverse pathologic factors or survival in resectable disease. Although not prognostic, the predictive value of HER2 status for response to trastuzumab in the adjuvant setting requires further investigation.

The role of local excision in invasive adenocarcinoma of the ampulla of Vater.

The role of local excision in invasive adenocarcinoma of the ampulla of Vater.

High expression of glycolytic and pigment proteins is associated with worse clinical outcome in stage III melanoma

There are insufficient numbers of prognostic factors available for prediction of clinical outcome in patients with stage III malignant cutaneous melanoma, even when known adverse pathological risk factors, such as macrometastasis, number of lymph node metastases, and ulceration are taken into consideration. The aim of this study was therefore to identify additional prognostic factors to better predict patients with a high risk of relapse, thus enabling us to better determine the need for adjuvant treatment in stage III disease. An RNA oligonucleotide microarray study was performed on first regional lymph node metastases in 42 patients with stage III melanoma: 23 patients with short-term survival (≤ 13 months) and 19 with long-term survival (≥ 60 months), to identify genes associated with clinical outcome. Candidate genes were validated by real-time PCR and immunohistochemical analysis. Several gene ontology (GO) categories were highly significantly differentially expressed including glycolysis (GO: 0006096; P<0.001) and the pigment biosynthetic process (GO: 0046148; P<0.001), in which overexpression was associated with short-disease-specific survival. Three overexpressed glycolytic genes, GAPDHS, GAPDH, and PKM2, and two pigment-related genes, TYRP1 and OCA2, were selected for validation. A significant difference in GAPDHS protein expression between short- and long-term survivors (P=0.021) and a trend for PKM2 (P=0.093) was observed in univariate analysis. Positive expression of at least two of four proteins (GAPDHS, GAPDH, PKM2, TYRP1) in immunohistochemical analysis was found to be an independent adverse prognostic factor for disease-specific survival (P=0.011). Our results indicate that this prognostic panel in combination with established risk factors may contribute to an improved prediction of patients with a high risk of relapse.

Carbonic anhydrase IX up-regulation is associated with adverse clinicopathologic and biologic factors in neuroblastomas

The overexpression of carbonic anhydrase IX, a hypoxia-induced enzyme, is associated with an adverse prognosis in many cancers. However, carbonic anhydrase IX expression in neuroblastoma, the most common extracranial pediatric tumor, has not been reported. Membranous and/or strong cytoplasmic carbonic anhydrase IX expression, assessed by immunohistochemistry, was present in 21 (23%) of 91 neuroblastomas but was absent in ganglioneuromas (n = 9). The proportion of neuroblastomas showing membranous carbonic anhydrase IX expression was higher in neuroblastomas with 1p deletion and MYCN amplification. Nuclear carbonic anhydrase IX expression was seen in less than 10% of ganglion cells in all ganglioneuromas. Of 91 neuroblastomas, 16 (18%) showed nuclear carbonic anhydrase IX expression in 10% or more tumoral cells. The proportion of neuroblastomas showing nuclear carbonic anhydrase IX expression was significantly higher in patients with adverse clinical (increasing stage and high-risk group), pathologic (unfavorable group and high mitosis-karyorrhexis-index), and biologic (MYCN-amplification and 1p deletion) factors. Carbonic anhydrase IX total protein levels, quantified by enzyme-linked immunosorbent assay, were higher in neuroblastomas (n = 49; geometric mean, 0.47 pg/µg; range, 0.0-6.52 pg/µg) than in ganglioneuromas (n = 6; geometric mean, 0.20 pg/µg; range, 0.09-0.47 pg/µg) and were significantly higher in MYCN-amplified neuroblastomas. Nuclear carbonic anhydrase IX expression was associated with a poorer overall survival (P = .003) and event-free survival (P = .004), although the relationships were no longer significant when adjusted for high-risk disease. There was no significant association of membranous carbonic anhydrase IX expression or higher-than-median total protein levels with overall survival or event-free survival. Carbonic anhydrase IX is expressed at significantly higher levels in neuroblastomas from patients with adverse clinicopathologic and biologic factors indicating that it is a biomarker of aggressive disease in neuroblastomas.

Abstract B46: Identification of biomarkers for stratification of Gleason score 7 patients using whole-transcriptome expression profiling

Abstract Motivations: Gleason score is the most prognostic variable in prostate cancer pathology. Patients with high Gleason (8+) are the most likely to experience biochemical recurrence (BCR), clinical progression (CP) and prostate-cancer specific mortality (PCSM), whereas patients with Gleason ≤6 are expected to have excellent long-term outcomes. However, the majority of prostate cancer patients are diagnosed with Gleason score 7, a heterogeneous group in terms of patient outcomes. In the absence of adverse pathological factors (APF, such as preoperative PSA, SM+, ECE and SVI) most Gleason 7 patients will have excellent outcomes. In contrast, Gleason 7 patients with APF are considered at high-risk for recurrence and therefore are candidates for adjuvant therapy. In this study, we have investigated whether a classifier based on differentially expressed genomic features could be used to improve prognostication of Gleason 7 patients, independent of APF. Methods: Two whole-transcriptome (1.4 million feature) oligonucleotide microarray expression datasets from radical prostatectomy specimens were analyzed. The first one (GEO accession: GSE21032) consisted of 125 fresh frozen (FF) samples from the MSKCC Oncogenome Project and the second dataset had 545 formalin-fixed-paraffin- embedded (FFPE) samples from the Mayo Clinic tumor registry. For genomic feature selection, differential expression in the FF dataset between Gleason ≤6 (n=40) and ≥8 (n=15) was assessed with false discovery rate adjusted t-tests (p&amp;lt;0.05). Next, a k-nearest neighbor (KNN) classifier was trained and tuned using the selected features to predict clinical progression (i.e., positive bone or CT scans after BCR) in the FFPE dataset, again using samples with Gleason score ≤6 (n=63) and ≥8 (n=211). The KNN classifier was evaluated on Gleason score 7 (n=209) FFPE samples (not used for training) using multivariable logistic regression. Results: The KNN classifier segregated the Gleason 7 samples into high and low risk CP groups. The KNN odds ratios were 2.9 (p&amp;lt;0.005), 2.1 (p&amp;lt;0.05) and 2.8 (p&amp;lt;0.05) for BCR, CP and PCSM end-points, respectively when comparing high and low risk groups. Multivariable analysis revealed that the KNN classifier was independently prognostic. Conclusions: A KNN classifier developed using differentially expressed genomic features significantly stratified Gleason score 7 patients for several clinically relevant endpoints. Future validation studies will address the utility of this classifier in predicting pathological Gleason score from biopsy specimens, which may be particularly useful for evaluation of biopsy Gleason 6 cases. In these patients, deferring prostatectomy in favour of active surveillance is an appealing treatment option unless the ‘true’ Gleason of the index lesion is in fact a Gleason 7 or higher, where immediate surgery is likely a life-saving procedure. Citation Format: Nicholas Erho, Thomas Sierocinski, Elai Davicioni, Robert B. Jenkins, Mercedeh Gadhessi, Christine Buerki, Ismael A. Vergara, Anamaria Crisan, Zaid Haddad, Benedikt Zimmermann, Anirban Mitra, Timothy J. Triche. Identification of biomarkers for stratification of Gleason score 7 patients using whole-transcriptome expression profiling [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr B46.

194 PRESENCE OF A HIGH GRADE TERTIARY GLEASON PATTERN UPGRADES THE GLEASON SUM SCORE AND INVERSELY ASSOCIATED WITH BIOCHEMICAL RECURRENCE-FREE SURVIVAL

You have accessJournal of UrologyProstate Cancer: Staging1 Apr 2011194 PRESENCE OF A HIGH GRADE TERTIARY GLEASON PATTERN UPGRADES THE GLEASON SUM SCORE AND INVERSELY ASSOCIATED WITH BIOCHEMICAL RECURRENCE-FREE SURVIVAL Polat Turker, Emine Bas, Suheyla Bozkurt, Bulent Gunlusoy, Arsenal Sezgin, Hakan Postaci, and Levent Turkeri Polat TurkerPolat Turker Tekirdag, Turkey More articles by this author , Emine BasEmine Bas Istanbul, Turkey More articles by this author , Suheyla BozkurtSuheyla Bozkurt Istanbul, Turkey More articles by this author , Bulent GunlusoyBulent Gunlusoy Izmir, Turkey More articles by this author , Arsenal SezginArsenal Sezgin Izmir, Turkey More articles by this author , Hakan PostaciHakan Postaci Izmir, Turkey More articles by this author , and Levent TurkeriLevent Turkeri Istanbul, Turkey More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.264AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Tumor heterogeneity is a common finding and led to realization of a tertiary Gleason component (TGC) in prostate cancer. In an attempt to further investigate its prognostic value, we analyzed the association of tertiary Gleason pattern in Gleason score less than/equal to 7 tumors with pathologic stage and biochemical disease-free survival. METHODS 331 radical prostatectomy specimens were analyzed retrospectively. The primary, secondary and the tertiary patterns were evaluated by reviewing all of the pathological slides. TGC was defined as Gleason grade pattern 4 or 5 for Gleason score less than 7 tumors and Gleason grade pattern 5 for Gleason score 7 tumors. The pathological prognostic factors, (extraprostatic extension, seminal vesicle and lymph node invasion, surgical margin status) of Gleason score less than 7, 3+4 and 4+3 tumors with or without TGC were compared. Biochemical recurrence free survival (BRFS) was calculated using Kaplan Meier method with log rank test and the influence of TGC was assessed in a Cox regression model. RESULTS TGC observed more frequently with higher Gleason scores (21% of the GS less than 7 cases, 23% of the GS 3+4 cases and 58% of the GS 4+3 cases). In terms of adverse pathological prognostic factors and BRFS, GS<7 tumors with TGC behaved significantly worse than GS<7 tumors without TGC (p=0.01 and p=0.001 respectively) with properties similar to GS 3+4 tumors without TGC. Gleason score 3+4 and 4+3 tumors without TGC were statistically similar and have better features than corresponding tumors of same Gleason score with TGC. Furthermore, Gleason score 7 tumors with TGC have similar features with GS 8-10 tumors. During follow-up 73 (22%) subjects had PSA recurrence. In the Cox regression model TGC was an independent variable for BRFS (HR=2.63, 95% CI=1.39–4.98, p=0.003). CONCLUSIONS According to the present study, 3 different prognostic groups were observed; good prognostic group: GS <7, intermediate prognostic group: GS<7+TGC, GS 3+4 and GS 4+3, and finally bad prognostic group: GS (3+4)+TGC, GS (4+3)+TGC,GS>7. Presence of a TGC appears to upgrade the total score and adjuvant treatment decisions may further be refined by considering the tertiary pattern. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e80-e81 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Polat Turker Tekirdag, Turkey More articles by this author Emine Bas Istanbul, Turkey More articles by this author Suheyla Bozkurt Istanbul, Turkey More articles by this author Bulent Gunlusoy Izmir, Turkey More articles by this author Arsenal Sezgin Izmir, Turkey More articles by this author Hakan Postaci Izmir, Turkey More articles by this author Levent Turkeri Istanbul, Turkey More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Embryonal rhabdomyosarcoma of the uterine cervix in a 47‐year‐old woman

Embryonal rhabdomyosarcoma (RMS) of the female genital tract usually occurs in the vagina during childhood. The uterine cervix as a primary site is rare, but is more frequent until the second decade of life. It usually has a good prognosis and the treatment is based on multidrug chemotherapy, radiotherapy and surgery. RMS accounts for <5% of all adult soft tissue sarcomas. Previous reports that included all primary sites showed a poorer five-year disease specific survival for adults with RMS when compared to the pediatric population. This difference has been attributed to a higher proportion of adverse prognostic clinical and pathological factors, and to inadequate treatment given to adults with RMS. A total of 115 patients with cervical embryonal RMS have previously been described; however, only 10 cases were reported in women older than 40 years. We present a 47-year-old woman treated with radical hysterectomy followed by adjuvant chemotherapy and review the current literature.

Presence of high grade tertiary Gleason pattern upgrades the Gleason sum score and is inversely associated with biochemical recurrence-free survival

ObjectivesTumor heterogeneity is a common finding and led to realization of a tertiary Gleason component (TGC) in prostate cancer. In an attempt to further investigate its prognostic value, we analyzed the association of tertiary Gleason pattern in Gleason score ≤ 7 tumors with pathologic stage and biochemical disease-free survival. Material and methodsA total of 331 radical prostatectomy specimens were analyzed retrospectively. The primary, secondary, and the tertiary patterns were evaluated by reviewing all of the pathologic slides. TGC was defined as Gleason grade pattern 4 or 5 for Gleason score < 7 tumors and Gleason grade pattern 5 for Gleason score 7 tumors. The pathologic prognostic factors, (extraprostatic extension, seminal vesicle and lymph node invasion, surgical margin status) of Gleason score < 7, 3+4, and 4+3 tumors with or without TGC were compared. Biochemical recurrence-free survival (BRFS) was calculated using Kaplan-Meier method with log rank test, and the influence of TGC was assessed in a Cox regression model. ResultsTGC observed more frequently with higher Gleason scores (21% of the GS < 7 cases, 23% of the GS 3+4 cases, and 58% of the GS 4+3 cases). In terms of adverse pathologic prognostic factors and BRFS, GS < 7 tumors with TGC behaved significantly worse than GS < 7 tumors without TGC (P = 0.01 and P = 0.001, respectively) with properties similar to GS 3+4 tumors without TGC. Gleason score 3+4 and 4+3 tumors without TGC were statistically similar and had better features than corresponding tumors of same Gleason score with TGC. Furthermore, Gleason score 7 tumors with TGC had similar features with GS 8–10 tumors. During follow-up, 73 (22%) subjects had PSA recurrence. In the Cox regression model TGC was an independent variable for BRFS (HR = 2.63, 95% CI = 1.39–4.98, P = 0.003). ConclusionAccording to the present study, 3 different prognostic groups were observed; good prognostic group: GS < 7, intermediate prognostic group: GS < 7+TGC, GS 3+4, and GS 4+3, and finally bad prognostic group: GS (3+4)+TGC, GS (4+3)+TGC, GS > 7. Presence of a TGC appears to upgrade the total score and adjuvant treatment decisions may further be refined by considering the tertiary pattern.

Tertiary Gleason Pattern 5 and Oncological Outcomes after Radical Prostatectomy

This study examined the rate of Gleason pattern 5 and the influence of tertiary Gleason pattern 5 on oncological outcomes. Four hundred sixty-six patients underwent a radical prostatectomy between 1993 and 2008. Each surgical specimen was reviewed and assessed for the tumor diameter, Gleason score (which was based on the 2005 International Society of Urological Pathology Consensus Conference criteria) and the percentage of Gleason pattern 5. The median patient age was 68.0 years old and the median prostate-specific antigen level was 9.28 ng/ml. A tertiary Gleason pattern 5 was present in 24.2% of patients with a Gleason score of <9; in 12.2% of patients with a Gleason score of 3 + 4 and in 45.9% of patients with a Gleason score of 4 + 3. A multivariate analysis showed that a tertiary Gleason pattern 5 was not independently associated with biochemical recurrence-free survival among patients in the Gleason score of 7 and 8 pN0 groups. One hundred eighty-seven patients had any rate of Gleason pattern 5 and significantly worse pathological factors, compared with patients who did not have this pattern. A multivariate analysis of all patients showed that the surgical margin, Gleason score, prostate-specific antigen level and pathological stage were all independent predictors of biochemical recurrence. However, the rate of Gleason pattern 5 was not an independent factor. Tertiary Gleason pattern 5 was not a significant predictive factor for biochemical recurrence. The rate of Gleason pattern 5 was associated with adverse pathological factors.