HER-2 Is an Independent Prognostic Factor in Endometrial Cancer: Association With Outcome in a Large Cohort of Surgically Staged Patients

2006 ◽  
Vol 24 (15) ◽  
pp. 2376-2385 ◽  
Author(s):  
Carl Morrison ◽  
Vanna Zanagnolo ◽  
Nilsa Ramirez ◽  
David E. Cohn ◽  
Nicole Kelbick ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Outcome Data ◽  
Large Cohort ◽  
Surgical Staging ◽  
Serous Carcinoma ◽  
Low Grade ◽  
Endometrioid Adenocarcinoma ◽  
High Grade ◽  
Her 2

Purpose To evaluate HER-2 expression and amplification in a large cohort of endometrial cancer with complete surgical staging and outcome data. Patients and Methods A tissue microarray was constructed of 483 patients with endometrial cancer of diverse histologic type and stage and tested for HER-2 expression and amplification using current standards of practice. There was outcome data for 83% of all patients and 81% with complete surgical staging. Results Both expression and amplification of HER-2 was associated with high-grade (P = .0001) and high stage (P = .0001) endometrial cancer. The highest rate of HER-2 expression and amplification was seen in serous carcinoma (43% and 29%), while grade 1 endometrioid adenocarcinoma showed the lowest levels (3% and 1%). For all histologic types, the rate of HER-2 expression and amplification was remarkably different (P < .0001) for grade 3 cancers (31% and 15%) versus grade 2 (7% and 3%) and grade 1 cancers (3% and 1%), with similar results for endometrioid type (P < .0001). Both HER-2 expression and amplification correlated with disease-specific survival and progression-free survival in univariate analyses. By multivariate analysis HER-2 expression in the presence of amplification (P = .012) correlated with overall survival, but not expression in the absence of amplification. Overall survival was significantly shorter (P = .0001) in patients who overexpressed (median, 5.2 years) and/or showed amplification of HER-2 (median, 3.5 years) versus those that did not (median of all cases, 13 years). Conclusion Our results would suggest that HER-2 is an important oncogene in high grade and stage endometrial cancer, but plays only a minor role in the much more common low grade and stage tumors that encompass the majority of clinical practice.

Should All Cases of High-Grade Serous Ovarian, Tubal, and Primary Peritoneal Carcinomas Be Reclassified as Tubo-Ovarian Serous Carcinoma?

2015 ◽  
Vol 25 (7) ◽  
pp. 1201-1207 ◽  
Author(s):  
Esther Louise Moss ◽  
Tim Evans ◽  
Philippa Pearmain ◽  
Sarah Askew ◽  
Kavita Singh ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clear Cell ◽  
Stage Iii ◽  
Serous Carcinoma ◽  
Low Grade ◽  
Type I ◽  
High Grade ◽  
Type Ii ◽  
Ovarian Serous Carcinoma ◽  
Significant Difference

IntroductionThe dualistic theory of ovarian carcinogenesis proposes that epithelial “ovarian” cancer is not one entity with several histological subtypes but a collection of different diseases arising from cells of different origin, some of which may not originate in the ovarian surface epithelium.MethodsAll cases referred to the Pan-Birmingham Gynaecological Cancer Centre with an ovarian, tubal, or primary peritoneal cancer between April 2006 and April 2012 were identified from the West Midlands Cancer Registry. Tumors were classified into type I (low-grade endometrioid, clear cell, mucinous, and low-grade serous) and type II (high-grade serous, high-grade endometrioid, carcinosarcoma, and undifferentiated) cancers.ResultsOvarian (83.5%), tubal (4.3%), or primary peritoneal carcinoma (12.2%) were diagnosed in a total of 583 woman. The ovarian tumors were type I in 134 cases (27.5%), type II in 325 cases (66.7%), and contained elements of both type I and type II tumors in 28 cases (5.7%). Most tubal and primary peritoneal cases, however, were type II tumors: 24 (96.0%) and 64 (90.1%), respectively. Only 16 (5.8%) of the ovarian high-grade serous carcinomas were stage I at diagnosis, whereas 240 (86.6%) were stage III+. Overall survival varied between the subtypes when matched for stage. Stage III low-grade serous and high-grade serous carcinomas had a significantly better survival compared to clear cell and mucinous cases,P= 0.0134. There was no significant difference in overall survival between the high-grade serous ovarian, tubal, or peritoneal carcinomas when matched for stage (stage III,P= 0.3758; stage IV,P= 0.4820).ConclusionsType II tumors are more common than type I and account for most tubal and peritoneal cancers. High-grade serous carcinomas, whether classified as ovarian/tubal/peritoneal, seem to behave as one disease entity with no significant difference in survival outcomes, therefore supporting the proposition of a separate classification of “tubo-ovarian serous carcinoma”.

Can the apparent diffusion coefficient differentiate the grade of endometrioid adenocarcinoma and the histological subtype of endometrial cancer?

2017 ◽  
Vol 59 (3) ◽  
pp. 363-370 ◽  
Author(s):  
Bin Yan ◽  
Tingting Zhao ◽  
Xiufen Liang ◽  
Chen Niu ◽  
Caixia Ding
Keyword(s):  
Diffusion Coefficient ◽  
Endometrial Cancer ◽  
Apparent Diffusion Coefficient ◽  
Low Grade ◽  
Endometrioid Adenocarcinoma ◽  
High Grade ◽  
Squamous Differentiation ◽  
Apparent Diffusion ◽  
Adc Values ◽  
Endometrial Cancers

Background Diffusion-weighted imaging (DWI) provides useful information for the identification of benign and malignant uterine lesions. However, the use of the apparent diffusion coefficient (ADC) for histopathological grading of endometrial cancer is controversial. Purpose To explore the use of ADC values in differentiating the preoperative tumor grading of endometrioid adenocarcinomas and investigate the relationship between the ADC values of endometrial cancer and the histological tumor subtype. Material and Methods We retrospectively evaluated 98 patients with endometrial cancers, including both endometrioid adenocarcinomas (n = 80) and non-endometrioid adenocarcinomas (n = 18). All patients underwent DWI procedures and ADC values were calculated. The Kruskal–Wallis test and the independent samples Mann–Whitney U test were used to compare differences in the ADC values between different tumor grades and different histological subtypes. Results The mean ADC values (ADCmean) for high-grade endometrioid adenocarcinomas were significantly lower than the values for low-grade tumors (0.800 versus 0.962 × 10–3 mm2/s) ( P = 0.002). However, no significant differences in ADCmean and minimum ADC values (ADCmin) were found between tumor grades (G1, G2, and G3) of endometrial cancer. Compared with endometrioid adenocarcinomas, the adenocarcinoma with squamous differentiation showed lower ADC values (mean/minimum = 0.863/0.636 versus 0.962/0.689 × 10–3 mm2/s), but the differences were not significant ( Pmean = 0.074, Pmin = 0.441). Moreover, ADCmean for carcinosarcomas was significantly higher than the value for G3 non-carcinosarcoma endometrial cancers (1.047 versus 0.823 × 10–3 mm2/s) ( P = 0.001). Conclusion The ADCmean was useful for identifying high-grade and low-grade endometrioid adenocarcinomas. Additionally, squamous differentiation may decrease ADCmean and ADCmin of endometrioid adenocarcinoma, and carcinosarcomas showed relatively high ADCmean.

Prognostic significance of obesity in high-grade serous carcinoma of the ovary

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16528-e16528 ◽  
Author(s):  
M. Schlumbrecht ◽  
D. Urbauer ◽  
D. Gershenson ◽  
R. Broaddus
Keyword(s):  
Ovarian Cancer ◽  
Body Mass Index ◽  
Overall Survival ◽  
Body Mass ◽  
Neoadjuvant Treatment ◽  
The United States ◽  
Wilcoxon Test ◽  
Serous Carcinoma ◽  
Low Grade ◽  
High Grade

e16528 Background: Obesity is an epidemic public health problem in the United States. In gynecologic oncology, obesity is an established risk factor for endometrial cancer. However, its role in the pathogenesis and survival in ovarian cancer is debated. Recent studies have attempted to elucidate a possible relationship, but variations in design and heterogeneity in patient characteristics make it difficult to draw definitive conclusions. The purpose of our study was to determine if body mass index at the time of treatment initiation for high grade serous ovarian carcinoma has an effect on patient outcome. Methods: Nine-hundred four patients treated for ovarian cancer at M.D. Anderson Cancer Center were identified between 2002 and 2007. Patients were excluded for low grade or non-serous histology, neoadjuvant treatment, or if presenting with recurrent disease. Clinicopathologic data were extracted by retrospective chart review. Patients were stratified by body mass index (BMI) as normal (BMI<25), overweight (BMI 25-<30), or obese (BMI>30). All were treated with primary cytoreduction and standard platinum/taxane chemotherapy. Chemotherapy was dosed using adjusted body weights. Outcomes included time to recurrence, overall survival, success of surgical debulking, and chemotherapeutic toxicities. Statistical analysis was performed using Fisher's exact test, Wilcoxon test, and Kaplan-Meier estimates. Results: A total of 127 patients were included for analysis. Patients were followed for a mean of 37 months (range 3–86 months). Twenty-one patients were obese (16.5%), and 35 were overweight (27.5%). Diabetes was more prevalent in the obese cohort (p = 0.0038). There was a trend towards greater likelihood of suboptimal debulking in obese patients, but this did not reach statistical significance (p = 0.06). BMI had no effect on recurrence-free survival (HR 0.69 [CI 0.39–1.23], p = 0.21) or overall survival (HR 0.95 [CI 0.68–2.43], p = 0.91). There was no difference in chemotherapy side effects or chemoresistance across BMI strata. Conclusions: Body mass index has no effect on survival in women with high grade serous ovarian cancer. Effectively managing comorbidities and ensuring adequate chemotherapy dosing in the obese patient is crucial for optimizing outcome. No significant financial relationships to disclose.

scholarly journals Risk-scoring models for individualized prediction of overall survival in low-grade and high-grade endometrial cancer

2014 ◽  
Vol 133 (3) ◽  
pp. 485-493 ◽  
Author(s):  
Mariam M. AlHilli ◽  
Andrea Mariani ◽  
Jamie N. Bakkum-Gamez ◽  
Sean C. Dowdy ◽  
Amy L. Weaver ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Low Grade ◽  
High Grade ◽  
Risk Scoring ◽  
Individualized Prediction

scholarly journals Trace Amine-Associated Receptor 1 (TAAR1) Is a Positive Prognosticator for Epithelial Ovarian Cancer

2021 ◽  
Vol 22 (16) ◽  
pp. 8479
Author(s):  
Tilman L. R. Vogelsang ◽  
Aurelia Vattai ◽  
Elisa Schmoeckel ◽  
Till Kaltofen ◽  
Anca Chelariu-Raicu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Epithelial Ovarian Cancer ◽  
Tnm Classification ◽  
Rank Correlation ◽  
University Hospital ◽  
Cancer Tissue ◽  
Low Grade ◽  
High Grade ◽  
Trace Amine

Trace amine-associated receptor 1 (TAAR1) is a Gαs- protein coupled receptor that plays an important role in the regulation of the immune system and neurotransmission in the CNS. In ovarian cancer cell lines, stimulation of TAAR1 via 3-iodothyronamine (T1AM) reduces cell viability and induces cell death and DNA damage. Aim of this study was to evaluate the prognostic value of TAAR1 on overall survival of ovarian carcinoma patients and the correlation of TAAR1 expression with clinical parameters. Ovarian cancer tissue of n = 156 patients who were diagnosed with epithelial ovarian cancer (serous, n = 110 (high-grade, n = 80; low-grade, n = 24; unknown, n = 6); clear cell, n = 12; endometrioid, n = 21; mucinous, n = 13), and who underwent surgery at the Department of Obstetrics and Gynecology, University Hospital of the Ludwig-Maximilians University Munich, Germany between 1990 and 2002, were analyzed. The tissue was stained immunohistochemically with anti-TAAR1 and evaluated with the semiquantitative immunoreactive score (IRS). TAAR1 expression was correlated with grading, FIGO and TNM-classification, and analyzed via the Spearman’s rank correlation coefficient. Further statistical analysis was obtained using nonparametric Kruskal-Wallis rank-sum test and Mann-Whitney-U-test. This study shows that high TAAR1 expression is a positive prognosticator for overall survival in ovarian cancer patients and is significantly enhanced in low-grade serous carcinomas compared to high-grade serous carcinomas. The influence of TAAR1 as a positive prognosticator on overall survival indicates a potential prognostic relevance of signal transduction of thyroid hormone derivatives in epithelial ovarian cancer. Further studies are required to evaluate TAAR1 and its role in the development of ovarian cancer.

Assessment of TP53 mutation using purified tissue samples of ovarian serous carcinomas reveals a higher mutation rate than previously reported and does not correlate with drug resistance

2008 ◽  
Vol 18 (3) ◽  
pp. 487-491 ◽  
Author(s):  
R. SALANI ◽  
R. J. KURMAN ◽  
R. GIUNTOLI ◽  
G. GARDNER ◽  
R. BRISTOW ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mutation Frequency ◽  
Clinical Stage ◽  
Serous Carcinoma ◽  
Low Grade ◽  
High Grade ◽  
Mutation Status ◽  
Tumor Dna ◽  
Serous Tumors

The TP53 mutation frequency in ovarian serous carcinomas has been reported to range between 50% and 80%, but a stringent analysis of TP53 using purified epithelial samples has not yet been performed to accurately assess the mutation frequency and to correlate it with the histologic grade. The purpose of this study was to assess the TP53 mutational profile in a relatively large series of high-grade (53 primary and 18 recurrent) and 13 low-grade ovarian serous tumors using DNA isolated from affinity-purified tumor cells and to correlate it with in vitro drug resistance. All samples were affinity purified, and the tumor DNA was analyzed for TP53 mutations in exons 4–9. In vitro drug resistance assays to carboplatin, cisplatin, paclitaxel, and taxotere were performed on the same tumor samples and correlated with the TP53 mutation status. TP53 mutations were detected in 57 (80.3%) of 71 high-grade carcinomas and in one (7.8%) of 13 low-grade serous tumors (an invasive low-grade serous carcinoma). The mutations were predominantly missense mutations (59.6%). TP53 mutations were associated with high-grade serous carcinomas and recurrent disease (P < 0.0001). There was no statistically significant correlation between TP53 mutation status and drug resistance assays or clinical stage (P > 0.25). The frequency of TP53 mutations using purified tumor DNA from ovarian serous carcinomas was 80.3%, which is much higher than previously reported. Furthermore, we found that TP53 is not directly involved in the development of drug resistance in high-grade ovarian serous carcinomas.

scholarly journals Redefining Stage I Endometrial Cancer: Incorporating Histology, a Binary Grading System, Myometrial Invasion, and Lymph Node Assessment

2013 ◽  
Vol 23 (9) ◽  
pp. 1620-1628 ◽  
Author(s):  
Joyce N. Barlin ◽  
Robert A. Soslow ◽  
Megan Lutz ◽  
Qin C. Zhou ◽  
Caryn M. St. Clair ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Myometrial Invasion ◽  
Staging System ◽  
Stage I ◽  
Low Grade ◽  
List Type ◽  
High Grade ◽  
High Grade Carcinoma ◽  
Concordance Probability ◽  
Grade 3

ObjectiveWe propose a new staging system for stage I endometrial cancer and compare its performance to the 1988 and 2009 International Federation of Gynecology and Obstetrics (FIGO) systems.MethodsWe analyzed patients with 1988 FIGO stage I endometrial cancer from January 1993 to August 2011. Low-grade carcinoma consisted of endometrioid grade 1 to grade 2 lesions. High-grade carcinoma consisted of endometrioid grade 3 or nonendometrioid carcinomas (serous, clear cell, and carcinosarcoma). The proposed system is as follows:IA. Low-grade carcinoma with less than half myometrial invasionIA1: Negative nodesIA2: No nodes removedIB. High-grade carcinoma with no myometrial invasionIB1: Negative nodesIB2: No nodes removedIC. Low-grade carcinoma with half or greater myometrial invasionIC1: Negative nodesIC2: No nodes removedID. High-grade carcinoma with any myometrial invasionID1: Negative nodesID2: No nodes removedResultsData from 1843 patients were analyzed. When patients were restaged with our proposed system, the 5-year overall survival significantly differed (P < 0.001): IA1, 96.7%; IA2, 92.2%; IB1, 92.2%; IB2, 76.4%; IC1, 83.9%; IC2, 78.6%; ID1, 81.1%; and ID2, 68.8%. The bootstrap-corrected concordance probability estimate for the proposed system was 0.627 (95% confidence interval, 0.590–0.664) and was superior to the concordance probability estimate of 0.530 (95% confidence interval, 0.516–0.544) for the 2009 FIGO system.ConclusionsBy incorporating histological subtype, grade, myometrial invasion, and whether lymph nodes were removed, our proposed system for stage I endometrial cancer has a superior predictive ability over the 2009 FIGO staging system and provides a novel binary grading system (low-grade including endometrioid grade 1–2 lesions; high-grade carcinoma consisting of endometrioid grade 3 carcinomas and nonendometrioid carcinomas).

Increased proteasome degradation of cyclin-dependent kinase inhibitor p27 is associated with a decreased overall survival in mantle cell lymphoma

Blood ◽  
2000 ◽  
Vol 95 (2) ◽  
pp. 619-626 ◽  
Author(s):  
Roberto Chiarle ◽  
Leo M. Budel ◽  
Jeffrey Skolnik ◽  
Glauco Frizzera ◽  
Marco Chilosi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Protein Degradation ◽  
Mantle Cell Lymphoma ◽  
Molecular Mechanisms ◽  
Kinase Inhibitor ◽  
Cell Lymphoma ◽  
Low Grade ◽  
High Grade ◽  
Ki 67 ◽  
Mantle Cell

Mantle cell lymphoma (MCL) is an aggressive neoplasm characterized by the deregulated expression of cyclin D1 by t(11;14). The molecular mechanisms responsible for MCL's clinical behavior remain unclear. The authors have investigated the expression of p53, E2F-1, and the CDK inhibitors p27 and p21 in 110 MCLs, relating their expression to proliferative activity (Ki-67). For comparison, they have similarly analyzed low-grade (12 MALT, 16 CLL/SLL) and high-grade (19 DLCL) lymphomas. p53 was detected more frequently in large-cell MCL (l-MCL; 5 of 7) than in classical MCL (s-MCL; 13 of 103) and DLCL (8 of 19). In MCL and DLCL, the percentage of E2F-1+ nuclei was high, correlating with high Ki-67 expression. Most MCLs (91 of 112) and DLCLs (12 of 19) showed a loss of p27; MALT and CLL/SLL, however, were p27 positive. Reverse transcription–polymerase chain reaction and in vitro protein degradation assays demonstrated that MCLs have normal p27 mRNA expression but increased p27 protein degradation activity via the proteasome pathway. Correlation of MCL p53 and p27 expression with clinical data showed an association between reduced overall survival rates and the overexpression of p53 (P = .001), the loss of p27 (P = .002), or both. Loss of p27 identified patients with a worse clinical outcome among p53 negative cases (P = .002). These findings demonstrated that MCL has a distinct cell cycle protein expression similar to that of high-grade lymphoma. The loss of p27 and the overexpression of p53 in MCL are prognostic markers that identify patients at high risk. The demonstration that low levels of p27 in MCL result from enhanced proteasome-mediated degradation should encourage additional clinical trials. (Blood. 2000;95:619-626)

Assessment of the Role of Intraoperative Frozen Section in Guiding Surgical Staging for Endometrial Cancer

2016 ◽  
Vol 26 (5) ◽  
pp. 918-923 ◽  
Author(s):  
Xiaoyuan Wang ◽  
Li Li ◽  
Janiel M. Cragun ◽  
Setsuko K. Chambers ◽  
Kenneth D. Hatch ◽  
...  
Keyword(s):  
Risk Factors ◽  
Endometrial Cancer ◽  
Tumor Size ◽  
Frozen Section ◽  
Medical Center ◽  
Myometrial Invasion ◽  
Surgical Staging ◽  
Endometrioid Adenocarcinoma ◽  
Intraoperative Frozen Section

ObjectiveThe aim of this study was to assess the role of intraoperative frozen section (FS) in guiding decision making for surgical staging of endometrioid endometrial cancer (EC).MethodsMedical records were collected retrospectively on 112 patients with endometrioid EC, who underwent total hysterectomy and bilateral salpingo-oophorectomy at the University of Arizona Medical Center from January 1, 2010, to December 31, 2014. Only patients with endometrioid adenocarcinoma, grade 1, less than 50% myometrial invasion, and tumor size less than 2 cm determined by intraoperative FS omitted lymphadenectomy; otherwise, surgical staging was performed with lymph node dissection. The FS results were compared with the permanent paraffin sections (PSs) to assess the diagnostic accuracy.ResultsThe concordance rate of different variables between FS and PS in EC was 100%, 89.3% (100/112), 97.3% (109/112), and 95.5% (107/112), respectively, with respecting to histological subtype, grade, myometrial invasion, and tumor size. Diagnostic accurate rate of combined risk factors deciding surgical staging at the time of FS was 95.5% (107/112), and the discordance rate of all risk factors considered between FS and PS was 4.5%, resulting 3 cases (2.7%) undertreated and 2 cases (1.8%) overtreated.ConclusionsDespite nonideal FS evaluation, intraoperative FS diagnosis for EC is highly reliable by providing guidance for the intraoperative decisions of surgical staging at our institution, and such guidelines may be referenced by the institutions with sufficient gynecologic pathology expertise.

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