L1-CAM as a predictor of survival in endometrial cancer: An analysis of The Cancer Genome Atlas (TCGA).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5599-5599
Author(s):  
Thanh Hue Dellinger ◽  
Charles Warden ◽  
Ernest Soyoung Han ◽  
Mark Tsuneo Wakabayashi
Keyword(s):  
Endometrial Cancer ◽  
Biomarker Discovery ◽  
Cox Regression ◽  
Myometrial Invasion ◽  
Good Survival ◽  
Peritoneal Cytology ◽  
Type I ◽  
High Grade ◽  
P Values ◽  
Cox Regression Analysis

5599 Background: Despite a good survival rate for early-stage endometrial cancers (ECs), the prognosis for advanced-stage ECs remains poor, with no biomarkers and few therapeutic options currently in existence. L1-cell adhesion molecule (L1-CAM), a glycoprotein which functions in adhesion and migration of tumor cells, has been associated with a poor prognosis in Type I endometrial cancer (ASCO 2011 Abstract #5091). We evaluated the role of L1-CAM among both Type I and II ECs in TCGA. Methods: Partek Genomics Suit was used to define differentially expressed genes with p-values for clinical associations (ANOVA with linear contrast for discrete variables and linear regression for continuous variables). Differences in survival between “high” and “low” expression groups (defined by median expression) were compared using Cox regression analysis, with p-values calculated via log-rank test, using the ‘survival’ package in R. Results: Of 451 downloadable tumor samples, 335 tumors with both clinical and gene expression data were analyzed. Median age was 63 yrs. (range 31-90 yrs.). Stage I, II, III, and IV comprised 65%, 7%, 23%, and 5%, respectively. 82% were endometrioid; 16% (n = 52) serous. Grade 1, 2, and 3 comprised 24%, 27%, and 49%, respectively. Median follow-up was 19.5 months. High L1-CAM expression was found in older (p = 0.0005), suboptimally debulked (p=0.002), and African-American patients (p = 0.0003), and those with high grade (p = 0.008), serous histology (p <0.00001), higher stage (p = 0.0004), positive peritoneal cytology (p = 0.007), deep myometrial invasion (p = 0.02), and positive pelvic (p = 0.003) and para-aortic lymph nodes (p = 0.002). High L1-CAM expression was associated with poor survival with a median overall survival of 17.2 months compared to 21.3 months for low L1-expressing endometrial tumors (HR= 3.1, CI=1.3 -7.3, p = 0.007). Conclusions: L1-CAM expression is associated with poorer survival and high-risk clinicopathologic factors in endometrial cancer. Its prevalence in Type II ECs, such as high-grade, serous ECs, makes it a particularly attractive target for both novel biomarker discovery and therapeutic targeting.

scholarly journals Clinicopathological analysis of early endometrial cancers

2016 ◽  
Author(s):  
Seema Singhal ◽  
Sunesh Kumar Jain ◽  
D. N. Sharma ◽  
Sandeep Mathur ◽  
Juhi Bharti ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Early Stage ◽  
Endometrial Adenocarcinoma ◽  
Tertiary Care ◽  
Myometrial Invasion ◽  
Poor Correlation ◽  
Histopathological Analysis ◽  
Peritoneal Cytology ◽  
Type I ◽  
Positive Peritoneal Cytology

Aim: The study objectives were evaluation of clinicopathological characteristics, correlations between the preoperative and postoperative tumor assessment in early stage endometrial cancer. Materials and Methods: We conducted a prospective descriptive study of 30 cases of endometrial cancer stage 1 examined and treated at a tertiary care teaching institute between the years 2014-15. Results: The patients’ mean age at the time of diagnosis was 56.4 years. The mean parity was two. Postmenopausal bleeding with or without abnormal vaginal discharge was the most frequent symptom; it was present in 84.7% of patients. Co morbidities like hypertension and diabetes were seen in 65% of women. 6/30 patients had family history of some malignancy. All the patients underwent Type I extrafascial hysterectomy with bilateral salpingo oophorectomy, one case had Type I extrafascial hysterectomy with infracolic omentectomy. A total of 10.6% cases had lymph nodes metastasis and none of these patients had ovarian metastasis or positive peritoneal cytology. None of the patients with superficial myometrial invasion (MI) had lymph node metastasis. None of the cases showed positive peritoneal cytology. Staging upgraded fom 1a to 1b in 50% of subjects after final histopathological analysis. One patient who was operated as endometrial hyperplasia with atypia actually had endometrial adenocarcinoma in the postoperative specimen. Conclusions: There is a poor correlation between the preoperative and the postoperative tumor assessment.

scholarly journals Clinicopathological analysis of early endometrial cancers

2016 ◽  
Author(s):  
Seema Singhal ◽  
Sunesh Kumar Jain ◽  
D. N. Sharma ◽  
Sandeep Mathur ◽  
Juhi Bharti ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Early Stage ◽  
Endometrial Adenocarcinoma ◽  
Tertiary Care ◽  
Myometrial Invasion ◽  
Poor Correlation ◽  
Histopathological Analysis ◽  
Peritoneal Cytology ◽  
Type I ◽  
Positive Peritoneal Cytology

Aim: The study objectives were evaluation of clinicopathological characteristics, correlations between the preoperative and postoperative tumor assessment in early stage endometrial cancer. Materials and Methods: We conducted a prospective descriptive study of 30 cases of endometrial cancer stage 1 examined and treated at a tertiary care teaching institute between the years 2014-15. Results: The patients’ mean age at the time of diagnosis was 56.4 years. The mean parity was two. Postmenopausal bleeding with or without abnormal vaginal discharge was the most frequent symptom; it was present in 84.7% of patients. Co morbidities like hypertension and diabetes were seen in 65% of women. 6/30 patients had family history of some malignancy. All the patients underwent Type I extrafascial hysterectomy with bilateral salpingo oophorectomy, one case had Type I extrafascial hysterectomy with infracolic omentectomy. A total of 10.6% cases had lymph nodes metastasis and none of these patients had ovarian metastasis or positive peritoneal cytology. None of the patients with superficial myometrial invasion (MI) had lymph node metastasis. None of the cases showed positive peritoneal cytology. Staging upgraded from 1a to 1b in 50% of subjects after final histopathological analysis. One patient who was operated as endometrial hyperplasia with atypia actually had endometrial adenocarcinoma in the postoperative specimen. Conclusions: There is a poor correlation between the preoperative and the postoperative tumor assessment.

scholarly journals Upregulation of Serum lncRNA DLEU1 Predicts Progression of Premalignant Endometrial Lesion and Unfavorable Clinical Outcome of Endometrial Cancer

2020 ◽  
Vol 19 ◽  
pp. 153303382096558
Author(s):  
Lixia Shan ◽  
Tao Zhao ◽  
Yu Wang
Keyword(s):  
Endometrial Cancer ◽  
Endometrial Hyperplasia ◽  
Cox Regression ◽  
Quantitative Polymerase Chain Reaction ◽  
Critical Role ◽  
Disease Free Survival ◽  
Lymphocytic Leukemia ◽  
Healthy Controls ◽  
Clinical Value ◽  
Cox Regression Analysis

Objective: Long non-coding RNAs (lncRNAs) play a critical role in tumorigenesis. Upregulation of lncRNA deleted in lymphocytic leukemia 1 (DLEU1) has been reported in endometrial cancer (EC) tissues. This prospective study aimed to determine the potential clinical significance of serum lncRNA DLEU1 in EC. Methods: The serum lncRNA DLEU1 level was detected in EC patients, patients with endometrial hyperplasia and healthy controls by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Then its clinical value in EC was further evaluated. Results: Our results demonstrated that serum lncRNA DLEU1 levels were significantly increased in patients with EC, and serum lncRNA DLEU1 showed good performance for discriminating EC patients from patients with endometrial hyperplasia and healthy controls. In addition, EC patients with advanced clinicopathological features had higher circulating lncRNA DLEU1 level than those with favorable clinical characteristics. Moreover, EC patients in the high serum lncRNA DLEU1 group suffered worse overall survival and disease-free survival than those in the low serum lncRNA DLEU1 group. Furthermore, multivariate cox regression analysis displayed that the serum lncRNA DLEU1 served as an independent prognostic factor for EC. Conclusions: Collectively, our study suggests that serum lncRNA DLEU1 is a novel and promising biomarker for prognostic estimation of EC.

scholarly journals High expression of fibroblast activation protein (FAP) predicts poor outcome in high-grade serous ovarian cancer

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Min Li ◽  
Xue Cheng ◽  
Rong Rong ◽  
Yan Gao ◽  
Xiuwu Tang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cox Regression ◽  
Paraffin Section ◽  
Progression Free Survival ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Systematic Analysis ◽  
Cox Regression Analysis ◽  
Genes Expression ◽  
High Level

Abstract Background High-grade serous ovarian cancer (HGSOC) is a fatal form of ovarian cancer. Previous studies indicated some potential biomarkers for clinical evaluation of HGSOC prognosis. However, there is a lack of systematic analysis of different expression genes (DEGs) to screen and detect significant biomarkers of HGSOC. Methods TCGA database was conducted to analyze relevant genes expression in HGSOC. Outcomes of candidate genes expression, including overall survival (OS) and progression-free survival (PFS), were calculated by Cox regression analysis for hazard rates (HR). Histopathological investigation of the identified genes was carried out in 151 Chinese HGSOC patients to validate gene expression in different stages of HGSOC. Results Of all 57,331 genes that were analyzed, FAP was identified as the only novel gene that significantly contributed to both OS and PFS of HGSOC. In addition, FAP had a consistent expression profile between carcinoma-paracarcinoma and early-advanced stages of HGSOC. Immunological tests in paraffin section also confirmed that up-regulation of FAP was present in advanced stage HGSOC patients. Prediction of FAP network association suggested that FN1 could be a potential downstream gene which further influenced HGSOC survival. Conclusions High-level expression of FAP was associated with poor prognosis of HGSOC via FN1 pathway.

Lymphadenectomy in Early-Stage Intermediate-/High-Risk Endometrioid Endometrial Cancer: Clinical Characteristics and Outcomes in an Australian Cohort

2017 ◽  
Vol 27 (7) ◽  
pp. 1379-1386 ◽  
Author(s):  
Rhonda Farrell ◽  
Suzanne C. Dixon ◽  
Jonathan Carter ◽  
Penny M. Webb
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
High Risk ◽  
Adjuvant Treatment ◽  
Cox Regression ◽  
Early Stage ◽  
Cox Regression Analysis ◽  
Cancer Study ◽  
Stage Ib ◽  
Australian Cohort

ObjectiveThe role of lymphadenectomy (LND) in early-stage endometrial cancer (EC) remains controversial. Previous studies have included low-risk patients and nonendometrioid histologies for which LND may not be beneficial, whereas long-term morbidity after LND is unclear. In a large Australian cohort of women with clinical early-stage intermediate-/high-risk endometrioid EC, we analyzed the association of LND with clinicopathological characteristics, adjuvant treatment, survival, patterns of disease recurrence, and morbidity.Materials and MethodsFrom a larger prospective study (Australian National Endometrial Cancer Study), we analyzed data from 328 women with stage IA grade 3 (n = 63), stage IB grade 1 to 3 (n = 160), stage II grade 1 to 3 (n = 71), and stage IIIC1/2 grade 1 to 3 (n = 31/3) endometrioid EC. Overall survival (OS) was estimated using Kaplan-Meier methods. The association of LND with OS was assessed using Cox regression analysis adjusted for age, stage, grade, and adjuvant treatment. The association with risk of recurrent disease was analyzed using logistic regression adjusted for age, stage, and grade. Morbidity data were analyzed using χ2 tests.ResultsMedian follow-up was 45.8 months. Overall survival at 3 years was 93%. Lymphadenectomy was performed in 217 women (66%), 16% of this group having positive nodes. Median node count was 12. There were no significant differences in OS between LND and no LND groups, or by number of nodes removed. After excluding stage IB grade 1/2 tumors, there was no association between LND and OS among a “high-risk” group of 190 women with a positive node rate of 24%. However, a similar cohort (n = 71) of serous EC in the Australian National Endometrial Cancer Study had improved survival after LND. Women who underwent LND had significantly higher rates of critical events (5% vs 0%, P = 0.02) and lymphoedema (23% vs 4%, P < 0.0001).ConclusionsIn this cohort with early-stage intermediate-/high-risk endometrioid EC, LND did not improve survival but was associated with significantly increased morbidity.

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).

Plasmin(ogen) serves as a favorable biomarker for prediction of survival in advanced high-grade serous ovarian cancer

2017 ◽  
Vol 398 (7) ◽  
pp. 765-773 ◽  
Author(s):  
Shuo Zhao ◽  
Julia Dorn ◽  
Rudolf Napieralski ◽  
Axel Walch ◽  
Sandra Diersch ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Positive Staining ◽  
Mrna Levels ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Data Set ◽  
Cox Regression Analysis ◽  
Kaplan Meier

Abstract In serous ovarian cancer, the clinical relevance of tumor cell-expressed plasmin(ogen) (PLG) has not yet been evaluated. Due to its proteolytic activity, plasmin supports tumorigenesis, however, angiostatin(-like) fragments, derived from PLG, can also function as potent anti-tumorigenic factors. In the present study, we assessed PLG protein expression in 103 cases of advanced high-grade serous ovarian cancer (FIGO III/IV) by immunohistochemistry (IHC). In 70/103 cases, positive staining of tumor cells was observed. In univariate Cox regression analysis, PLG staining was positively associated with prolonged overall survival (OS) [hazard ratio (HR)=0.59, p=0.026] of the patients. In multivariable analysis, PLG, together with residual tumor mass, remained a statistically significant independent prognostic marker (HR=0.49, p=0.009). In another small patient cohort (n=29), we assessed mRNA expression levels of PLG by quantitative PCR. Here, elevated PLG mRNA levels were also significantly associated with prolonged OS of patients (Kaplan-Meier analysis; p=0.001). This finding was validated by in silico analysis of a microarray data set (n=398) from The Cancer Genome Atlas (Kaplan-Meier analysis; p=0.031). In summary, these data indicate that elevated PLG expression represents a favorable prognostic biomarker in advanced (FIGO III/IV) high-grade serous ovarian cancer.

EVALUATION OF MYOMETRIAL INVASION AND CERVICAL INVOLVEMENT IN TYPE I ENDOMETRIAL CANCER USING DIFFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING

2020 ◽  
pp. 4-6
Author(s):  
HARIYONO WINARTO ◽  
BRIAN PRIMA ARTHA ◽  
SAHAT B. MATONDANG ◽  
TANTRI HELLYANTI ◽  
ARIA KEKALIH
Keyword(s):  
Magnetic Resonance Imaging ◽  
Endometrial Cancer ◽  
Magnetic Resonance ◽  
Cancer Patients ◽  
Myometrial Invasion ◽  
Type I ◽  
Resonance Imaging ◽  
Diffusion Weighted ◽  
Weighted Magnetic Resonance Imaging ◽  
Cervical Involvement

Objective: Surgical procedure and adjuvant treatment of type I endometrial cancer were affected by some variables assessed preoperatively. Diffusion-weighted magnetic resonance imaging (DWI) is a promising modality in evaluating myometrial invasion and cervical involvement, investigating the diagnostic values of DWI in assessing myometrial invasion and cervical involvement. Methods: A cross-sectional study was conducted. This study involved all type I endometrial cancer patients in Dr. Cipto Mangunkusumo Hospital from April 2016 until April 2019. The depth of myometrial invasion and cervical involvement was examined using 1.5-T MR unit. The result was compared to the surgical pathologic findings as the reference standard. Results: 34 types I endometrial cancer patients were enrolled in this study. The sensitivity of DWI in evaluating myometrial invasion and cervical involvement in type I endometrial cancer was 94.12% and 57.14%, while the specificity was 64.71% and 92.59%, respectively. Conclusion: DWI can provide reliable prognostic variable information about the myometrial invasion and cervical involvement in the preoperative preparation of endometrial cancer patients.

Pattern Recognition to Prognosticate Endometrial Cancer: The Science Behind the Art of Office Hysteroscopy—A Retrospective Study

2016 ◽  
Vol 26 (4) ◽  
pp. 705-710 ◽  
Author(s):  
Hsuan Su ◽  
Deeksha Pandey ◽  
Ling-Yu Liu ◽  
Chih-Feng Yen ◽  
Chin-Jung Wang ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Invasive Disease ◽  
Type I ◽  
High Grade ◽  
Office Hysteroscopy ◽  
Group 2 ◽  
Grade 3 ◽  
Pattern Group ◽  
Histopathological Grading ◽  
Group 1

ObjectiveThis study aimed to evaluate a specific glomerular pattern for prognostication of endometrial cancer (EC).Materials and MethodsThe office hysteroscopy’s picture and video of 4197 women were reviewed, 48 women who were suspected of type I EC were analyzed: 26 have glomerular pattern (group 1) and 22 without it (group 2).ResultsThe histopathological grading after hysterectomy with glomerular pattern had grade 2 or grade 3 disease on final histology (n = 25; 96%). The sensitivity and specificity of this test were 84.6% and 81.8%, respectively, with a likelihood ratio of 4:6 in predicting and prognosticating those women who have high-grade tumor or invasive disease.ConclusionsThis hysteroscopic picture might be used as a novel marker for risk stratification of EC.

scholarly journals Whole genome analysis identifies the association of TP53 genomic deletions with lower survival in Stage III colorectal cancer

2019 ◽  
Author(s):  
Li C Xia ◽  
Paul Van Hummelen ◽  
Matthew Kubit ◽  
Hojoon Lee ◽  
John M Bell ◽  
...  
Keyword(s):  
High Efficiency ◽  
Biomarker Discovery ◽  
Cox Regression ◽  
Stage Iii ◽  
Whole Genome ◽  
Whole Genome Analysis ◽  
High Coverage ◽  
Cox Regression Analysis ◽  
Genomic Deletions ◽  
Low Coverage

ABSTRACTDNA copy number aberrations (CNA) were frequently observed in colorectal cancers (CRC). There is an urgent call for CNA-based biomarkers in clinics, in particular for Stage III CRC, if combined with imaging or pathologic evidence, promise more precise care at the timing. We conducted this Stage III specific biomarker discovery with a cohort of 134 CRCs, and with a newly developed high-efficiency CNA profiling protocol. Specifically, we developed the profiling protocol for tumor-normal matched tissue samples based on low-coverage clinical whole-genome sequencing (WGS). We demonstrated the protocol’s accuracy and robustness by a systematic benchmark with microarray, high-coverage whole-exome and -genome approaches, where the low-coverage WGS-derived CNA segments were highly accordant (PCC>0.95) with those derived from microarray, and they were substantially less variable if compared to exome-derived segments. A lasso-based model and multivariate cox regression analysis identified a chromosome 17p loss, containing the TP53 tumor suppressor gene, that was significantly associated with reduced survival (P=0.0139, HR=1.688, 95% CI = [1.112-2.562]), which was validated by an independent cohort of 187 Stage III CRCs. In summary, the new low-coverage WGS protocol has high sensitivity, high resolution and low cost and the identified 17p-loss is an effective poor prognosis marker for Stage III patients.

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