Tumor Marker Profile Research Articles

Tumor markers in non-small cell lung cancer spine metastasis: an assessment of prognosis and overall survival.

The identification of gene mutations in the modern medical workup of metastatic spine tumors has become more common but has not been highly utilized in surgical planning. Potential utility of these genetic markers as surrogates for cancer behavior in current prognosis scoring systems and overall survival (OS) remains underexplored in existing literature. This study seeks to investigate the association of frequently identified tumor markers, EGFR, ALK, and PD-L1, in metastatic non-small cell lung cancer (NSCLC) to the spine with Tokuhashi prognosis scoring and OS. Patients with NSCLC metastasis to spine were identified through chart review. EGFR, ALK, and PD-L1 wild type vs. mutant type were identified from targeted chemotherapy genetic testing. Multiple linear regression was performed to assess gene profile contributions to Tokuhashi score. Cox Proportional Hazards models were generated for each tumor marker to assess the relationship between each marker and OS. A total of 119 patients with NSCLC spine metastasis were identified. We employed a multiple linear regression analysis to investigate the influence of EGFR, ALK, and PD-L1 genotypes on the Tokuhashi score, revealing statistically significant relationships overall (p = 0.002). Individual genotype contributions include EGFR as a non-significant contributor (p = 0.269) and ALK and PD-L1 as significant contributors (p = 0.037 and p = 0.001 respectively). Overall survival was not significantly associated with tumor marker profiles through Kaplan-Meier analysis (p = 0.46) or by multivariable analysis (p = 0.108). ALK and PD-L1 were significantly associated with Tokuhashi score while EGFR was not. Tumor markers alone were not predictive of OS. These findings indicate that genetic markers found in NSCLC metastases to the spine may demonstrate prognostic value. Therefore, employing standard tumor markers could enhance the identification of appropriate surgical candidates, although they demonstrate limited effectiveness in predicting overall survival.

Different Characteristics of Serum Alfa Fetoprotein and Serum Des-gamma-carboxy Prothrombin in Resected Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) mainly develops in the damaged liver from hepatitis C virus (HCV) or hepatitis B virus (HBV) infection in Japan. On the other hand, the occurrence of HCCs derived from the liver without viral infection has recently been increasing. Our aim was to identify characteristics specific to HCCs with virus-infected liver (HCC-BC) or those with non-B- and non-C-infected liver (HCC-NBNC), Patients and Methods: We collected preoperative serum α-fetoprotein (AFP) and Des-Gamma-Carboxy Prothrombin (DCP), also known as PIVKA-II values from surgically resected HCC cases during 1994-2017 in our department. Preoperative serum AFP values of HCC-BC cases (n=284) were higher compared to HCC-NBNC cases (n=88) (p=0.016), whereas serum DCP values of HCC-NBNC cases were higher compared to HCC-BC cases (p<0.001). Multivariable analyses indicated that abnormal serum AFP [hazard ratio (HR)=1.46, 95% conficdence interval (CI)=1.03-2.07, p=0.035) was one of the significant recurrence-free survival predictors of HCC-BC cases, while abnormal serum DCP (HR=4.99, 95%CI=1.91-13.01, p=0.001) was one of the significant recurrence-free survival predictors of HCC-NBNC cases. HCC-NBNC cases have a different tumor marker profile from HCC-BC cases. Elevated DCP could be both a diagnostic and prognostic marker of HCC-NBNC patients.

Multimodality Imaging Approach to Ovarian Neoplasms with Pathologic Correlation.

Ovarian neoplasms can be categorized on the basis of histopathologic features into epithelial surface cell tumors, germ cell tumors, sex cord-stromal tumors, and metastases. While their imaging appearance is often nonspecific, it closely parallels the gross pathologic appearance, and radiologic-pathologic correlation is helpful to aid in a deeper understanding of the subtypes. Epithelial cell neoplasms are the most common category, and they can be benign, borderline, or malignant. Specific subtypes include serous (most common), mucinous, seromucinous, endometrioid, clear cell, Brenner, and undifferentiated. High-grade serous cystadenocarcinoma accounts for the majority of malignant ovarian tumors and the most ovarian cancer deaths. While serous neoplasms are often unilocular and bilateral, mucinous neoplasms are larger, unilateral, and multilocular. Solid components, thickened septa, and papillary projections, particularly with vascularity, indicate borderline or malignant varieties. Endometrioid and clear cell carcinomas can arise within endometriomas. Fibrous tumors (cystadenofibroma, adenofibroma, fibroma or fibrothecoma, and Brenner tumors) demonstrate low T2-weighted signal intensity of their solid components, while teratomas contain lipid. The nonspecific imaging appearance of additional malignant ovarian germ cell tumors can be narrowed with tumor marker profiles. Sex cord-stromal tumors are often solid, and secondary signs from their hormonal secretion can be a clue to their diagnosis. The authors review the anatomy of the ovary and distal fallopian tube, the proposed origins of the histologic subtypes of tumors, the clinical features and epidemiology of ovarian neoplasms, and the applications of US, CT, and MRI in imaging ovarian neoplasms. The main focus is on the radiologic and pathologic features of the multiple ovarian neoplasm subtypes. An algorithmic approach to the diagnosis of ovarian neoplasms is presented. Online supplemental material is available for this article. ©RSNA, 2020.

The Impact of Preoperative CA19-9 and CEA on Outcomes of Patients with Intrahepatic Cholangiocarcinoma.

The objective of the current study was to assess the impact of serum CA19-9 and CEA and their combination on survival among patients undergoing surgery for intrahepatic cholangiocarcinoma (ICC). Patients who underwent curative-intent resection of ICC between 1990 and 2016 were identified using a multi-institutional database. Patients were categorized into four groups based on combinations of serum CA19-9 and CEA (low vs. high). Factors associated with 1-year mortality after hepatectomy were examined. Among 588 patients, 5-year OS was considerably better among patients with low CA19-9/low CEA (54.5%) compared with low CA19-9/high CEA (14.6%), high CA19-9/low CEA (10.0%), or high CA19-9/high CEA (0%) (P < 0.001). No difference in 1-year OS existed between patients who had either high CA19-9 (high CA19-9/low CEA:70.4%) or high CEA levels (low CA19-9/high CEA:72.5%) (P = 0.92). Although patients with the most favorable tumor marker profile (low CA19-9/low CEA) had the best 1-year survival (87.9%), 15.1% (n = 39) still died within a year of surgery. Among patients with low CA19-9/low CEA, a high neutrophil-to-lymphocyte ratio (NLR) (odds ratio 1.09; 95% confidence interval 1.03-1.64) and large size tumor (odds ratio 3.34; 95% confidence interval 1.40-8.10) were associated with 1-year mortality (P < 0.05). Patients with either a high CA19-9 and/or high CEA had poor 1-year survival. High NLR and large tumor size were associated with a greater risk of 1-year mortality among patients with favorable tumor marker profile.

Abstract P4-10-30: PD-L1 expression in tumor infiltrating lymphocytes (TILs) inversely correlates with androgen receptor (AR) expression in HER2-positive breast cancer

Abstract Background: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer accounts for 20-30% of breast carcinomas and is associated with a poor prognosis. While anti-HER2 targeted therapies have improved outcomes within this group, a subset of these tumors eventually develop resistance urgently requiring novel therapeutic options. In addition to classic HER2+ subtype, estrogen receptor (ER)-positive and HER2-positive tumors (luminal B) are another subtype of HER2 expressing breast carcinomas which could also benefit from additional therapies. Targeting the androgen receptor (AR) pathway and the PD-L1 axis may represent potential new therapeutic strategies in breast cancer. Our group previously reported that AR expression is seen in ¾ of HER2+ carcinomas and is more common in luminal B compared to classic HER2+ tumors. In this report, we evaluated expression of PD-L1 in tumor infiltrating lymphocytes (TILs) in both classic HER2 + and Luminal B subtypes of breast carcinomas and correlated the expression of PD-L1 with AR expression in these tumors. Methods: The study population consisted of 114 patients with HER2-positive invasive breast carcinoma diagnosed from 2009-2014 at Northwestern Memorial Hospital. Electronic medical records were reviewed for patient demographics (mean age 54, range 23-80). Pathologic tumor characteristics (histologic type, size, and grade) and tumor marker profile (ER and HER2) were evaluated. Tissue microarrays were constructed (3 cores from each case to account for tumor heterogeneity) for immunohistochemical evaluation of AR and PD-L1. AR was graded as positive when at least 1% of tumor cells showed nuclear immunoreactivity. For PD-L1, the extent of staining (0%=0, 1-10%=1, 11-50%=2, and 51-100%=3) and staining intensity (0, 1+, 2+, 3+) were assessed in TILs. Then a composite score (CS) was calculated by multiplying extent and intensity results (range 0-9; 0-3=negative, 4-9=positive). Results: Of the 114 studied breast carcinoma cases, 54 were classic HER2+ tumors (47%) and 60 were luminal B (53%) tumors. Approximately 69% of classic HER2+ and 87% of luminal B cases were positive for AR. Of interest, in classic HER2+ cases, the expression of PD-L1 in TILs was inversely correlated with the expression of AR, with 82% (14/17) of AR- tumors being positive for PD-L1 in TILs compared to only 46% (17/37) of AR+ tumors with PD-L1 expression in TILs (p&amp;lt;0.01). No association of expression of PD-L1 in TILs with AR expression was observed in luminal B cases (62% in AR+ versus 50% in AR- tumors; p=0.70). Moreover, in classic HER2+/AR- group, grade 3 tumors were seen almost exclusively in the PD-L1 expressing group (13 versus 3), in contrast to the equal number of grade 3 tumors in classic HER2+/AR+ group regardless of PD-L1 expression in TILs (14 versus 14). No association of the PD-L1 expression with age, race, and tumor histologic types was observed in classic HER2+/AR+ or classic HER2+/AR- cases. Conclusions: Our results demonstrated that the expression of PD-L1 in TILs was inversely correlated with the expression of AR in classic HER2 positive tumors but not in luminal B tumors. We also found that in classic HER2+/AR- group, grade 3 tumors were seen almost exclusively in the PD-L1 expression group. Our findings add to the body of knowledge of the molecular mechanisms that drive the different molecular subtypes of breast carcinomas and raise the interesting possibility that new treatment strategies such as targeting the PD-L1 axis may show more benefit against the AR negative subtype of the classic HER2 positive carcinomas. Citation Format: Tiansheng Shen, Jennifer L. Pincus, Kalliopi P. Siziopikou. PD-L1 expression in tumor infiltrating lymphocytes (TILs) inversely correlates with androgen receptor (AR) expression in HER2-positive breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-10-30.

A Case of Combined-histology Lung Carcinoma (Adenocarcinoma Plus Small Cell Carcinoma) Presenting with Changes in the Tumor Marker Profile and Histological Findings During the Clinical Course

A Case of Combined-histology Lung Carcinoma (Adenocarcinoma Plus Small Cell Carcinoma) Presenting with Changes in the Tumor Marker Profile and Histological Findings During the Clinical Course

Severe Acute Myocardial Infarction during Induction Chemotherapy for Retroperitoneal Germ Cell Tumor : A Case Report

A 37-year-old man presented at our hospital. Pathological examination of a right orchiectomy specimen, radiographic examination, and tumor marker profile resulted in a diagnosis of retroperitoneal nonseminomatous germ cell tumor (intermediate risk according to IGCC classification). Laboratory testing revealed mild elevation of low density lipoprotein cholesterol. Induction chemotherapy with bleomycin, etoposide and cisplatin (BEP) was started, but he complained of chest pain on day 10 of the second cycle of BEP. We immediately started cardiac monitoring. One hour later, he suffered cardiac arrest due to ventricular fibrillation. Fortunately, sinus rhythm was restored after defibrillation. A diagnosis of acute myocardial infarction (AMI) with total occlusion at the mid-portion of the left anterior descending coronary artery was established by coronary angiography. After percutaneous transluminal coronary angioplasty was successfully performed, he recovered uneventfully. The induction chemotherapy was re-started 19 days after AMI. To avoid endothelial damage by bleomycin, we elected to treat with etoposide, ifosfamide, and cisplatin (VIP). After two further courses of VIP, the patient underwent resection of retoperitoneal tumor and achieved complete remission. The patient has remained disease-free during 3 years follow up without recurrence of AMI.

Pre-treatment double- or triple-positive tumor markers are predictive of a poor outcome for patients undergoing radiofrequency ablation for hepatocellular carcinoma.

We evaluated the therapeutic effect of radiofrequency ablation (RFA) on hepatocellular carcinoma (HCC) according to the number of positive tumor markers. The subjects of this study were 160 patients who underwent percutaneous and surgical RFA for HCC. Patients were divided into negative (n=51), single- (n=69), double- (n=31), and triple-positive (n=9) tumor marker groups according to the pre-treatment expression of these markers. We looked for any relationships among clinical parameters, outcomes, and tumor markers. The 3-year recurrence-free and overall survival rates of the negative, single-, double-, and triple-positive groups were 30, 19, 16, and 11% (P=0.02), and 94, 88, 67, and 37% (P<0.001), respectively. The 2-year local recurrence rates were 6.5, 0, 41.2, and 61.9%, respectively (P<0.001). Multivariate analysis revealed that a double- or triple-positive pre-treatment tumor marker profile was independently associated with local recurrence [hazard ratio (HR) 5.48, 95% confidence interval (CI) 2.44-12.33, P<0.001] and overall survival (HR 4.21, 95% CI 1.89-9.37, P<0.001). RFA may not be suitable for patients with HCC who have pre-treatment expression of ≥two of these tumor markers.

Abstract 2271: bcl-2 expression in HER2-positive breast carcinoma subtypes

Abstract Background: HER2-positive breast cancers comprise 20-30% of all breast cancers; amplification of HER2 confers a poorer prognosis. While treatment with anti-HER2 targeted therapies has dramatically improved outcomes in this group, a significant subset of patients develops resistance, highlighting the need for novel therapeutic options. In addition, like triple negative breast carcinomas, HER2-positive invasive carcinomas also consist of different intrinsic subtypes with different responses to therapy and different overall prognosis. Finally, recent reports suggest that bcl-2 expression contributes to resistance to anti-HER2 therapies. In this study, we evaluated expression of bcl-2 in HER2-positive breast tumors and correlated the expression of bcl-2 with HER2 subtype, patient demographics and histologic and molecular characteristics. Design: The study population consisted of 114 patients with HER2-positive invasive breast carcinoma treated with surgical excision or mastectomy at Northwestern Memorial Hospital (2009-14) (mean age 53, range 18-80). Electronic medical records were reviewed for patient demographics. Pathologic tumor characteristics (histologic type, size, grade, lymph node status) and tumor marker profile (ER, PR, p53 and Ki-67) were evaluated. Tissue microarrays were constructed (3 cores from each case to account for tumor heterogeneity) for immunohistochemical evaluation of bcl-2 (Dako, clone 124). Results: Overall, these HER2-pos breast carcinomas were almost exclusively of ductal histologic type (101/114, 88.6%). Almost ¾ of the cases were poorly differentiated, grade 3 carcinomas (83/114, 73%), while the other 31 were grade 2 tumors. No grade 1 tumors were seen. bcl-2 was expressed in 64/114 (56%) of the HER2-pos carcinomas. No association of the bcl-2 expression with age, race, tumor size, lymph node status, p53 expression, or Ki-67 proliferation index was seen. Of interest, this sample of HER2-pos carcinomas was almost equally balanced between ER-neg/HER2-pos (HER2 subtype) and ER-pos/HER2-pos (Luminal B subtype), 54 vs 60 cases respectively. bcl-2 was differentially expressed in these two HER2-pos tumor subtypes: only 9/54 (14%) of the HER2 subtype expressed bcl-2 compared to 55/64 (85.9%) of the Luminal B subtype (p&amp;lt;0.0001). Conclusions: 1. bcl-2 is expressed in just over half of the HER2-pos carcinomas. 2. bcl-2 expression is far more common in Luminal B compared to the HER2-pos subtype of breast carcinomas. 3. bcl-2 expression does not appear to have a differential expression between age or racial groups and does not correlate with tumor size or lymph node status. Our findings add to the understanding of the molecular mechanisms that drive the different subtypes of HER2-pos breast carcinomas and raise the possibility that bcl-2 targeted therapies may lead to novel therapeutic approaches for the management of subgroups of patients with HER2-pos breast tumors. Citation Format: Kalliopi P. Siziopikou, Alexandra Larson, Luis Z. Blanco, Virginia Kaklamani. bcl-2 expression in HER2-positive breast carcinoma subtypes. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2271.

MP06-05 PRECYSTECTOMY EPITHELIAL TUMOR MARKER RESPONSE TO NEOADJUVANT CHEMOTHERAPY AND ITS EFFECT ON ONCOLOGICAL OUTCOMES IN UROTHELIAL BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Epidemiology & Evaluation II1 Apr 2016MP06-05 PRECYSTECTOMY EPITHELIAL TUMOR MARKER RESPONSE TO NEOADJUVANT CHEMOTHERAPY AND ITS EFFECT ON ONCOLOGICAL OUTCOMES IN UROTHELIAL BLADDER CANCER Soroush T Bazargani, Thomas G. Clifford, Hooman Djaladat, Anne Schuckman, Sarmad Sadeghi, Tanya Dorff, David Quinn, and Siamak Daneshmand Soroush T BazarganiSoroush T Bazargani More articles by this author , Thomas G. CliffordThomas G. Clifford More articles by this author , Hooman DjaladatHooman Djaladat More articles by this author , Anne SchuckmanAnne Schuckman More articles by this author , Sarmad SadeghiSarmad Sadeghi More articles by this author , Tanya DorffTanya Dorff More articles by this author , David QuinnDavid Quinn More articles by this author , and Siamak DaneshmandSiamak Daneshmand More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2166AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We have previously reported that elevated pre-cystectomy serum levels of epithelial tumor markers predict worse oncological outcome in patients with invasive urothelial bladder cancer (UBC). Herein, we evaluated the effect of neoadjuvant chemotherapy (NAChT) on elevated tumor marker levels and their association with oncological outcomes. METHODS Under IRB approval, serum levels of Carbohydrate Antigen 125 (CA-125), Carbohydrate Antigen 19-9 (CA 19-9) and Carcinoembryonic Antigen (CEA) were prospectively measured in 368 patients with invasive UBC from August 2011 through August 2015. In the subgroup undergoing NAChT, markers were measured prior to the first and after the last cycle of chemotherapy (before cystectomy). RESULTS 93 (25%) patients underwent NAChT, of whom 51 had a complete tumor marker profile before and after therapy and 24 (47%) of them had one or more elevated pre-NAChT tumor markers (3 missing post NAChT markers). The mean age was 67 years (range: 33-82), with 12 (57%) males. After completion of chemotherapy, 9/21 (43%) patients normalized their tumor markers, while 12/21 (57%) had one or more persistently elevated markers (p=0.004). There was no difference in pathological stage between groups (p=0.16). Median serum level of CA19-9 was significantly different before and after NAChT (137 vs. 19.3. respectively; p=0.03), while CA125 and CEA were not (Figure 1). Further analysis showed that tumor marker response is strongly correlated with disease recurrence/progression (45% in responders vs. 91% in non-responders at a median time 111 vs. 71 days respectively; p=0.01). Two patients that died in the normalized tumor marker group had tumor marker relapse at recurrence prior to their death. CONCLUSIONS To our knowledge, this is the first pilot study showing tumor marker response to NAChT. The results of this cohort suggest that patients with persistently elevated markers following NAChT have a very poor prognosis following cystectomy. There may be a promising role for these markers in identifying patients whose tumor is resistant to chemotherapy. A larger, controlled study with longer follow up is needed to determine their role in predicting survival. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e68 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Soroush T Bazargani More articles by this author Thomas G. Clifford More articles by this author Hooman Djaladat More articles by this author Anne Schuckman More articles by this author Sarmad Sadeghi More articles by this author Tanya Dorff More articles by this author David Quinn More articles by this author Siamak Daneshmand More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Abstract P6-01-21: C-myc and bcl-2 overexpression in HER2-positive breast carcinomas

Abstract Background: Gene amplification plays a significant role in the transcriptional regulation of the genome; in breast cancer, amplification of the HER2 gene occurs in 20-30% of patients and confers a poor prognosis. Trastuzumab is now widely used in HER2-positive breast carcinomas and has significantly changed outcomes in this aggressive subtype of breast cancer. C-myc, another oncogene, is reported to be amplified in breast cancer; c-myc regulates cell proliferation. Bcl-2, the prototype anti-apoptotic gene, is overexpressed in human breast carcinomas. The anti-apoptotic action of bcl-2 is located downstream from HER2 and may serve as a potential drug target. This study evaluated the rate of c-myc and bcl-2 overexpression in a cohort of HER2-amplified breast carcinomas and correlated the dysregulation of these genes with patient demographics and histologic characteristics. Design: The study population consisted of 96 patients with HER2-positive invasive breast carcinoma treated with surgical excision or mastectomy at Northwestern Memorial Hospital (2009-12) (mean age 53, range 18-80). Electronic medical records were reviewed for patient demographics. Pathologic tumor characteristics (histologic type, size, grade, lymph node status) and tumor marker profile at the time of diagnosis (ER, PR, p53 and ki-67) were evaluated. Tissue microarrays were constructed (3 cores from each case to account for tumor heterogeneity) for immunohistochemical evaluation of c-myc (Epitomics, clone V69) and bcl-2 (DAKO, clone 124). Results: Overall, these HER2-amplified breast carcinomas were almost exclusively infiltrating ductal carcinomas (92/96, 96%) of high histologic grade: 68/96 (71%) were grade 3, while the other 28 were grade 2 tumors. C-myc was overexpressed in 49/96 (51%) of the cases and bcl-2 was expressed in 60/96 (62%). There was no association of c-myc or bcl-2 expression with age, patient race, tumor grade, tumor size, lymph node status, p53 expression or ki-67 proliferation index. Expression of both c-myc and bcl-2 was seen in 30/96 (31%) of the cases. Of interest, c-myc-positive/bcl-2-positive tumors more often had positive lymph nodes and higher ki-67 proliferation index compared to tumors with c-myc-negative/bcl-2-negative phenotype (46.7% v 29.4% and 75.8% v 56.2% respectively). Conclusions: (1) C-myc is expressed in over 50% and bcl-2 in over 60% of HER2-amplified carcinomas. (2) C-myc and bcl-2 expression do not appear to have differential expression between age groups or racial groups and do not correlate with histologic tumor characteristics. (3) HER2-amplified carcinomas expressing both c-myc and bcl-2 are highly proliferative tumors with a high rate of lymph node positivity. These findings suggest that coupled c-myc and bcl-2 overexpression may contribute to the biologic aggressiveness of HER2-amplified breast carcinomas. Additional studies into the molecular mechanisms that drive HER2-amplified tumors are currently underway in this aggressive subtype of breast cancer. Citation Format: Alexandra L Larson, Denise M Scholtens, Adriana A Rosca, Virginia Kaklamani, Kalliopi P Siziopikou. C-myc and bcl-2 overexpression in HER2-positive breast carcinomas [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-01-21.

PD23-09 EPITHELIAL TUMOR MARKERS (CA 125, CA 19-9 AND CEA) TRENDS IN PATIENTS UNDERGOING TREATMENT FOR INVASIVE BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Detection and Screening I1 Apr 2015PD23-09 EPITHELIAL TUMOR MARKERS (CA 125, CA 19-9 AND CEA) TRENDS IN PATIENTS UNDERGOING TREATMENT FOR INVASIVE BLADDER CANCER Soroush T. Bazargani, Swar Shah, Hamed Ahmadi, Anne Schuckman, Jie Cai, Gus Miranda, Tanya Dorff, Sarmad Sadeghi, David Quinn, Hooman Djaladat, and Siamak Daneshmand Soroush T. BazarganiSoroush T. Bazargani More articles by this author , Swar ShahSwar Shah More articles by this author , Hamed AhmadiHamed Ahmadi More articles by this author , Anne SchuckmanAnne Schuckman More articles by this author , Jie CaiJie Cai More articles by this author , Gus MirandaGus Miranda More articles by this author , Tanya DorffTanya Dorff More articles by this author , Sarmad SadeghiSarmad Sadeghi More articles by this author , David QuinnDavid Quinn More articles by this author , Hooman DjaladatHooman Djaladat More articles by this author , and Siamak DaneshmandSiamak Daneshmand More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1425AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Epithelial tumor markers, like CA 125, CA 19-9 and CEA have been associated with worse oncological outcomes in patients with invasive bladder cancer (BC). Herein, we report marker response to treatment and their association with oncological outcomes. METHODS Using our IRB approved BC database, we identified 252 patients who had available CA 125, CA 19-9, and CEA levels before and after cystectomy for urothelial BC. Patients undergoing neoadjuvant chemotherapy (NAChT) had tumor makers measured prior to the first and after the last cycle of chemotherapy (before cystectomy). Patients were followed closely and marker levels were checked on each visit in those with elevated pre-cystectomy markers, and at the time of relapse in others. RESULTS A total of 202 patients (mean age at cystectomy 70, 78% male) with available markers at follow-up were included in the study. 26 patients had complete tumor marker profile before and after NAChT. 12/26 had one or more elevated tumor markers prior to NAChT. After completing chemotherapy, 7/12 (58%) had normalized tumor markers. Of the 5 (42%) patients who still had elevated levels, 4 died (3 cancer-related) at a median of 5 months, compared to only 1 death in the group with normalized markers following NAChT. Of those who underwent cystectomy only, 139 (69%) patients had normal markers while 63 (31%) had at least one abnormal pre-cystectomy marker. Cox Regression models showed the risk of recurrence was 4 times higher, with at least one elevated tumor marker (p=0.001) with a hazard ratio for death of 19.7 (p<0.0001) (Figures 1, 2). Elevated pre-cystectomy levels of CA19-9 and CA125 were associated with recurrence (p<0.01), and elevated levels of each of the three markers prior to cystectomy were strongly predictive of mortality (p <0.002). CONCLUSIONS The study confirms the predictive role of these three epithelial tumor markers for mortality and the association of CA125 and CA 19-9 with recurrence in invasive bladder cancer. Patients with persistently elevated markers postoperatively have a poor prognosis. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e483-e484 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Soroush T. Bazargani More articles by this author Swar Shah More articles by this author Hamed Ahmadi More articles by this author Anne Schuckman More articles by this author Jie Cai More articles by this author Gus Miranda More articles by this author Tanya Dorff More articles by this author Sarmad Sadeghi More articles by this author David Quinn More articles by this author Hooman Djaladat More articles by this author Siamak Daneshmand More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Molecular cues on obesity signals, tumor markers and endometrial cancer.

Tumor markers are important tools for early diagnosis, prognosis, therapy response and endometrial cancer monitoring. A large number of molecular and pathologic markers have been described in types I and II endometrial cancers, which has served to define the main oncogenic, epidemiological, genetic, clinical and histopathological features. Ongoing attempts to stratify biological markers of endometrial cancer are presented. However, data on changes in tumor marker profiles in obesity-related endometrial cancer are scarce. Obesity is a pandemic in Western countries that has an important impact on endometrial cancers, albeit through not very well-defined mechanisms. Although endometrial cancer is more common in Caucasian women, higher mortality is found in African Americans who also show higher incidence of obesity. Here, we describe how obesity signals (estrogen, leptin, leptin induced-molecules, Notch; cytokines and growth factors) could affect endometrial cancer. Leptin signaling and its crosstalk may be associated to the more aggressive and poor prognosis type II endometrial cancer, which affects more postmenopausal and African-American women. In this regard, studies on expression of novel molecular markers (Notch, interleukin-1 and leptin crosstalk outcome) may provide essential clues for detection, prevention, treatment and prognosis.

Multiplexed Analysis of Serum Breast and Ovarian Cancer Markers by Means of Suspension Bead–quantum Dot Microarrays

Multiplexed analysis of cancer markers is crucial for early tumor diagnosis and screening. We have designed lab-on-a-bead microarray for quantitative detection of three breast cancer markers in human serum. Quantum dots were used as bead-bound fluorescent tags for identifying each marker by means of flow cytometry. Antigen-specific beads reliably detected CA 15-3, CEA, and CA 125 in serum samples, providing clear discrimination between the samples with respect to the antigen levels. The novel microarray is advantageous over the routine single-analyte ones due to the simultaneous detection of various markers. Therefore the developed microarray is a promising tool for serum tumor marker profiling.

NI-35 * ESTABLISHMENT OF BRAIN TUMOR PHOSPHOLIPID IMAGING PROFILING BY MALDI MASS SPECTROMETRY - A MOUSE MODEL

Malignant brain tumor is a common and severe primary brain tumor with a high recurrence rate and a poor prognosis. Because of the infiltrative nature of malignant brain tumor, tissues surrounding the tumor that remain after surgery might contribute to recurrence. Develop potential tumor marker profiles may help to distinguish tumor and healthy tissues in the brain. Since aberrant lipid metabolism in tumor cells has been commonly observed in cancer cells, it is likely that the altered lipid metabolism will also be seen in the in situ tumors. To visualize such change, we profiled the phospholipids in the brain tumor created in a mouse model with MALDI-MS. We also visualized the distribution of aberrant phospholipids in the brain tumor by MALDI-MS imaging. The MALDI profiling and imaging were also carried out in sections after desalting to remove the interference from the endogenous alkali metal ions, and reveal additional low abundant lysophospholipids within the tumor. Tumor specific phosphatidylcholine, lysophosphatidylcholine and sphingomyelin distribution also show regional variation within the brain tumor region. Whether the combination of these species can serve as the marker for pathological differential grading requires further verification.

Renal epithelioid angiomyolipoma with a negative premelanosome marker immunoprofile: a case report and review of the literature

IntroductionThe rare variant of renal epithelioid/pleomorphic angiomyolipoma has been reported in approximately 120 cases. One of the most important characteristics to differentiate these tumors from other renal cell neoplasms is their typical reactivity to premelanosome antigens. If such a tumor does not stain for HMB-45 or Melan-A, a specific diagnosis of epithelioid pleomorphic angiomyolipoma cannot be made with certainty.Case presentationWe present here what is, to the best of our knowledge, the first case of epithelioid/pleomorphic angiomyolipoma of the kidney in a 50-year-old Caucasian man with no history of tuberous sclerosis, and with a tumor marker profile negative for several premelanosome antigens. The tumor was composed of sheets of pleomorphic, round to polygonal epithelioid cells with prominent eosinophilic cytoplasm, large nuclei, many multinucleated, and very prominent nucleoli. There were prominent vessels and rare interspersed smooth muscle fibers, but adipocytes were not identified. A tumor marker profile showed tumor cell reactivity for CD68, calponin and focally for CD10. Intervening smooth muscle was reactive with smooth muscle actin. The tumor lacked reactivity for melanin-associated antigens HMB-45 and Melan-A, and for CD31, pan-cytokeratin (AE1/3) and desmin. Electron microscopic examination of tumor cells confirmed the presence of premelanosome-like granules.ConclusionsBased on the characteristic microscopic appearance of this tumor, and its overall tumor marker profile, we concluded this was a renal epithelioid/pleomorphic angiomyolipoma with a negative premelanosome antigen phenotype.

Bone metastases in patients with relapsed/refractory germ cell tumors (GCT) undergoing first salvage chemotherapy: A retrospective analysis of a large international database.

4597 Background: Bone metastases (mets) are rare events in GCT patients (pts) and data on characteristics, risk factors, treatment and outcome in these pts are largely missing. Methods: A subgroup of 104 ptswith bone metsfrom the IPFSG database was analyzed. All patients experienced unequivocal relapse/progression after &gt; 3 cycles of cisplatin-based chemotherapy and received conventional-dose (CDCT) or high-dose salvage chemotherapy (HDCT). Results: 104 / 1594 pts presented with bone mets (6,5%) at first relapse. Histology was pure seminoma in 26%, and non-seminoma in 74%. At initial diagnosis, 54% of pts had presented with "poor risk" according to IGCCCG. Overall response rate (ORR; CR+PR) to 1st-line chemotherapy was 89%. Median PFS after primary treatment was 3 months (range 0 - 140). Bone mets at first relapse were accompanied by abdominal, lung, mediastinal, liver and brain mets in 54%, 48%, 28%, 36%, and 14%, respectively. Tumor marker profiles were heterogeneous (elevation of AFP / ß-HCG: 51% / 37%). Salvage treatment was CDCT in 34%, and HDCT in 66% of pts. ORR to salvage chemotherapy was 68% for the total cohort, and 43% vs. 81% for CDCT vs. HDCT (p&lt;.01). For the total cohort, 2y-PFS and 5y-OS were 24% and 16%, respectively. 2y-PFS and 5y-OS were significantly higher in pts after HDCT compared to CDCT (2y-PFS 29% vs. 14%, p=.01; 5y-OS 19% vs. 9%, p=.04). Conclusions: Pts relapsing with bone mets after platinum-based CTX were characterized by "poor risk" disease at initial diagnosis, but characteristics at first relapse were heterogeneous. Treatment response and outcome was improved in pts with HDCT compared to CDCT. Further prospective evaluation of characteristics and treatment approaches in GCT pts with bone mets is warranted.

Association between Recency of Last Pregnancy and Biologic Subtype of Breast Cancer

Breast cancers (BCs) diagnosed after a recent pregnancy display features associated with poor prognosis, including hormone receptor negativity, but other tumor markers have not been examined. We sought to define the tumor marker profile of these cancers, including HER-2 and p53 expression, and examine the time interval over which this adverse profile is observed, relative to last pregnancy. A prospectively maintained database was reviewed to identify women with a BC diagnosis between 1998 to 2011. Parous women were categorized on the basis of the interval between pregnancy and BC diagnosis; 0-2 years, >2-5 years, >5-10 years, and >10-15 years. Tumor characteristics of parous cases were compared to those of nulliparous BC patients, who were frequency matched by age. A total of 175 parous and 114 nulliparous women were identified. Women who were 0-2 years from last parity at the time of BC diagnosis were the only group who were more likely than control women to have grade 3 tumors (P<0.01), positive lymph nodes (P=0.02), and triple negative tumors (P=0.01, odds ratio 3.2, 95% confidence interval 1.2-8.5). There was no difference noted in HER-2 or p53 status relative to interval from pregnancy. BC diagnosed within 2 years of pregnancy is more likely to have poor prognostic features and to be triple negative. More work is needed to delineate the time frame of pregnancy-associated BC and to define them on a molecular level, so as to devise better prevention and therapy for this devastating problem.

Acute scrotal pain with a twist

Intratesticular lesions identified on ultrasound are usually malignant. It presents a particular dilemma to the surgeon when conservative approach is considered. A 55-year-old smoker with peripheral vascular disease had attended the accident and emergency with acute left hemiscrotal pain of 24-h duration. Clinical examination revealed a swollen, tender hemiscrotum. Ultrasound had demonstrated a hypo-echoic lesion in the testis measuring 2 x 1.8 cm. This was reported as possible infarct and managed conservatively. On review after 4 weeks, the patient was still symptomatic with persistent dull pain. A repeat scan in 4 weeks showed persistence of the lesion raising the possibility of tumour. Tumour marker profile was not elevated. The patient had a radical orchidectomy and the histology showed segmental infarction of the testis with thrombosis of the segmental testicular vessels. Peripheral vascular disease can cause segmental infarction of the testis due to the end arterial blood supply; in these cases, magnetic resonance scan can be diagnostic. Once confirmed, segmental infarcts can be safely managed conservatively.

Laparoscopic management of giant ovarian cysts in adolescents.

A laparoscopic approach to giant ovarian cysts in girls, when the cyst's size exceeds the umbilicus, may be difficult regarding the risk of cyst rupture and limited working space. We present a series of three 12-year-old girls with giant ovarian cysts treated by percutaneous drainage under ultrasonographic guidance followed by laparoscopic resection. Clinical, laboratory and radiological diagnosis showed no signs of malignancy. After induction of general endotracheal anaesthesia, under ultrasonographic guidance, a 10 F vesicostomy catheter was placed into the cyst. Two to 4 l of serous (in one case mucinous) fluid were drained from the cyst. During laparoscopy, the abdominal cavity was inspected by the scope and no signs of malignancy were found. The laparoscopic procedure was completed with excision of the cyst and keeping some ovarian tissue in all cases. No intraoperative complications were observed. The mean operation time was 73 min. Pathological examination revealed a mature cystic teratoma in two cases and mucinous cystadenoma in one. The postoperative recovery was uneventful in all girls and they were discharged home on postoperative day 2-4 with minimal pain. The ultrasound scans and tumour markers were normal on follow-up after 3 and 6 months. Laparoscopic excision of giant ovarian cysts after ultrasound-guided drainage seems to be a safe and applicable treatment modality in pre-menarchal girls with a normal tumour marker profile and benign features of the cyst, excluding the possibility of malignancy.