Transcriptional Characterization of Stage I Epithelial Ovarian Cancer: A Multicentric Study

Stage I epithelial ovarian cancer (EOC) represents about 10% of all EOCs. It is characterized by a complex histopathological and molecular heterogeneity, and it is composed of five main histological subtypes (mucinous, endometrioid, clear cell and high, and low grade serous), which have peculiar genetic, molecular, and clinical characteristics. As it occurs less frequently than advanced-stage EOC, its molecular features have not been thoroughly investigated. In this study, using in silico approaches and gene expression data, on a multicentric cohort composed of 208 snap-frozen tumor biopsies, we explored the subtype-specific molecular alterations that regulate tumor aggressiveness in stage I EOC. We found that single genes rather than pathways are responsible for histotype specificities and that a cAMP-PKA-CREB1 signaling axis seems to play a central role in histotype differentiation. Moreover, our results indicate that immune response seems to be, at least in part, involved in histotype differences, as a higher immune-reactive behavior of serous and mucinous samples was observed with respect to other histotypes.

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Patterns of Lymph Node Metastases in Apparent Stage I Low-Grade Epithelial Ovarian Cancer: A Multicenter Study

Annals of Surgical Oncology ◽

10.1245/s10434-017-5919-y ◽

2017 ◽

Vol 24 (9) ◽

pp. 2720-2726 ◽

Cited By ~ 20

Author(s):

Lucas Minig ◽

Florian Heitz ◽

David Cibula ◽

Jamie N. Bakkum-Gamez ◽

Anna Germanova ◽

...

Keyword(s):

Ovarian Cancer ◽

Lymph Node ◽

Epithelial Ovarian Cancer ◽

Multicenter Study ◽

Lymph Node Metastases ◽

Stage I ◽

Low Grade ◽

Node Metastases

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lncRNAs as Novel Indicators of Patients' Prognosis in Stage I Epithelial Ovarian Cancer: A Retrospective and Multicentric Study

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-16-1402 ◽

2016 ◽

Vol 23 (9) ◽

pp. 2356-2366 ◽

Cited By ~ 31

Author(s):

Paolo Martini ◽

Lara Paracchini ◽

Giulia Caratti ◽

Maurizia Mello-Grand ◽

Robert Fruscio ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Stage I ◽

Multicentric Study

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Incidence of Lymph Node Metastases in Apparent Early-Stage Low-Grade Epithelial Ovarian Cancer: A Comprehensive Review

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000787 ◽

2016 ◽

Vol 26 (8) ◽

pp. 1407-1414 ◽

Cited By ~ 16

Author(s):

Victor Lago ◽

Lucas Minig ◽

Christina Fotopoulou

Keyword(s):

Ovarian Cancer ◽

Lymph Node ◽

Epithelial Ovarian Cancer ◽

Retrospective Studies ◽

Early Stage ◽

Stage I ◽

Surgical Staging ◽

Low Grade ◽

Early Stage Disease ◽

True Incidence

ObjectivesThis study aimed to determine the incidence of lymph node (LN) metastases in presumed stage I-II low-grade epithelial ovarian cancer (EOC).MethodsEligible studies were identified from MEDLINE and EMBASE (time frame, 2015–1975), that analyzed patients with clinical or radiologic presumed early-stage EOC who underwent a complete pelvic and para-aortic lymphadenectomy as part of their surgical staging. The number and site of dissected and involved LNs and the correlation with overall outcome are analyzed. The termlow gradeand also the older termwell differentiatedwere used.ResultsThirteen of 978 identified studies were selected, and 13 of 75 studies were identified as eligible. A total of 1403 patients were analyzed in these 13 retrospective studies. The final International Federation of Gynecology and Obstetrics staging after completed surgical staging was I to II in 912 patients (65%). A total of 338 patients (24%) had grade 1 tumors whereas 473 patients (34%) had grade 2, and 502 patients (36%) had grade 3 tumors. Systematic lymphadenectomy was performed in 1159 patients (83%), whereof 1142 (82%) were pelvic and para-aortic LN dissections.In 185 patients (13%), an upstaging from an apparent clinical stage I-II to IIIC occurred because of LN involvement: 64 (35%) of the patients had only pelvic LNs metastases, 69 (37%) had only para-aortic LNs metastasis, and 51 (28%) had both a pelvic and para-aortic LN involvement. When analyzing only the patients with low-grade (grade 1 as the old classification) presumed early-stage disease (n = 273), only 8 patients (2.9%; range, 0–6.2) were identified with LNs metastases present.ConclusionsThe incidence of occult LN metastases in apparent early-stage low-grade EOC is 2.9% in a metaanalysis of retrospective studies. Future larger-scale prospectively assessed studies with established surgical quality of the LN dissection are warranted to establish the true incidence of LN metastasis in presumed early low-grade disease.

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PATTERNS OF LYMPH NODE METASTASES IN APPARENT STAGE I LOW-GRADE EPITHELIAL OVARIAN CANCER: A MULTICENTER STUDY.

10.26226/morressier.599bdc79d462b80296ca1877 ◽

2017 ◽

Author(s):

Lucas Minig

Keyword(s):

Ovarian Cancer ◽

Lymph Node ◽

Epithelial Ovarian Cancer ◽

Multicenter Study ◽

Lymph Node Metastases ◽

Stage I ◽

Low Grade ◽

Node Metastases

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Targeted Selected Reaction Monitoring Verifies Histology Specific Peptide Signatures in Epithelial Ovarian Cancer

Cancers ◽

10.3390/cancers13225713 ◽

2021 ◽

Vol 13 (22) ◽

pp. 5713

Author(s):

Leena Liljedahl ◽

Johan Malmström ◽

Björg Kristjansdottir ◽

Sofia Waldemarson ◽

Karin Sundfeldt

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Clinical Symptoms ◽

Simultaneous Detection ◽

Selected Reaction Monitoring ◽

Molecular Heterogeneity ◽

Low Grade ◽

Reaction Monitoring ◽

High Grade ◽

Specific Peptide

Epithelial ovarian cancer (OC) is a disease with high mortality due to vague early clinical symptoms. Benign ovarian cysts are common and accurate diagnosis remains a challenge because of the molecular heterogeneity of OC. We set out to investigate whether the disease diversity seen in ovarian cyst fluids and tumor tissue could be detected in plasma. Using existing mass spectrometry (MS)-based proteomics data, we constructed a selected reaction monitoring (SRM) assay targeting peptides from 177 cancer-related and classical proteins associated with OC. Plasma from benign, borderline, and malignant ovarian tumors were used to verify expression (n = 74). Unsupervised and supervised multivariate analyses were used for comparisons. The peptide signatures revealed by the supervised multivariate analysis contained 55 to 77 peptides each. The predictive (Q2) values were higher for benign vs. low-grade serous Q2 = 0.615, mucinous Q2 = 0.611, endometrioid Q2 = 0.428 and high-grade serous Q2 = 0.375 (stage I–II Q2 = 0.515; stage III Q2 = 0.43) OC compared to benign vs. all malignant Q2 = 0.226. With targeted SRM MS we constructed a multiplexed assay for simultaneous detection and relative quantification of 185 peptides from 177 proteins in only 20 µL of plasma. With the approach of histology-specific peptide patterns, derived from pre-selected proteins, we may be able to detect not only high-grade serous OC but also the less common OC subtypes.

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

International Journal of Molecular Sciences ◽

10.3390/ijms22168479 ◽

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.

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Low-grade serous epithelial ovarian cancer: a comprehensive review and update for radiologists

Insights into Imaging ◽

10.1186/s13244-021-01004-7 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Sofia Amante ◽

Filipa Santos ◽

Teresa Margarida Cunha

Keyword(s):

Ovarian Cancer ◽

Serous Carcinoma ◽

Low Grade ◽

Resonance Imaging ◽

Clinicopathologic Characteristics ◽

Borderline Tumour ◽

Molecular Features ◽

Serous Epithelial Ovarian Cancer ◽

The Difference

AbstractLow-grade serous carcinoma (LGSC) is an infrequent subtype of ovarian cancer, corresponding to 5% of epithelial neoplasms. This subtype of ovarian carcinoma characteristically has molecular features, pathogenesis, clinical behaviour, sensitivity to chemotherapy, and prognosis distinct to high-grade serous carcinoma (HGSC). Knowing the difference between LGSC and other ovarian serous tumours is vital to guide clinical management, which currently is only possible histologically. However, imaging can provide several clues that allow differentiating LGSC from other tumours and enable precise staging and follow-up of ovarian cancer treatment. Characteristically, LGSC appears as mixed lesions with variable papillary projections and solid components, usually in different proportions from those detected in serous borderline tumour and HGSC. Calcified extracellular bodies, known as psammoma bodies, are also a common feature of LGSC, frequently detectable within lymphadenopathies and metastases associated with this type of tumour. In addition, the characterisation of magnetic resonance imaging enhancement also plays an essential role in calculating the probability of malignancy of these lesions. As such, in this review, we discuss and update the distinct radiological modalities features and the clinicopathologic characteristics of LGSC to allow radiologists to be familiarised with them and to narrow the differential diagnosis when facing this type of tumour.

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