Low grade serous ovarian cancer – A rare disease with increasing therapeutic options

Zwimpfer, Tibor Andrea; Tal, Ori; Geissler, Franziska; Coelho, Ruimário Inácio; Rimmer, Natalie; Jacob, Francis; Heinzelmann‐Schwarz, Viola

doi:10.1016/j.ctrv.2022.102497

Cited by 11 publications

(12 citation statements)

References 83 publications

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“…FAK has been found to promote oncogenesis in diverse cancers including ovarian by increasing the invasive potential of tumor cells through extracellular matrix remodeling as well as by modulating PI3K and MAPK signaling pathways to promote tumor cell aggressivity 25,26 . Notably, MAPK signaling has been shown to be hyperactivated in LGSOC tumors 3,26 and targeting MAPK signaling using clinical inhibitors of MAPK signaling, i.e. MEK inhibitors has led to multiple clinical trials focused on exploiting this therapeutic vulnerability in LGSOC 3,26 .…”

Section: Discussionmentioning

confidence: 99%

Deep Quantitative Proteomics Identifies Conserved Proteome Alterations in Low and High-Grade Serous Ovarian Cancers

Tarney,

Mhawech-Fauceglia,

Ogata

et al. 2024

Preprint

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Low-grade serous ovarian carcinoma (LGSOC) is a rare and largely chemoresistant subtype of epithelial ovarian cancer. Unlike treatment for high-grade serous ovarian cancer (HGSOC), management options for LGSOC patients are limited, in part, due to a lack of deep molecular characterization of this disease. To address this limitation, we performed quantitative mass spectrometry-based proteomic analyses of whole tissue collections of tumors harvested from LGSOC (n=12) and HGSOC (n=24) patients or normal fallopian tube tissues (n=12) from women with benign disease. We quantified 7,043 proteins across all patient samples and unsupervised analyses revealed proteome alterations distinctly stratify fallopian tube tissue, LGSOC, and HGSOC tumors. Proteins elevated in LGSOC compared to HGSOC tumors (LIMMA adjusted p < 0.05) were enriched for pathways regulating cilium assembly and included a pathway regulating activation of FAK1 by MET, a therapeutic target in LGSOC. Using data from an independent proteomic analysis of LGSOC (n=14) and HGSOC (n=30) tumors, we identified 330 co-altered proteins between LGSOC and HGSOC tumors exhibiting high quantitative correlation (Spearman Rho = 0.803, P < 2.2E10-16). Among these, MUC16 was identified as significantly elevated (>1.7 log2-fold) in LGSOC versus HGSOC. Immunohistochemistry analysis of MUC16 verified the increased abundance in LGSOC tissues and identified that MUC16 staining patterns in LGSOC are uniquely apical compared to HGSOC (Fishers Exact p = 0.001). Our deep proteomic analyses identifies highly-conserved proteome alterations distinguishing LGSOC from HGSOC tumors, including candidates regulating FAK1 signaling as well as a novel identification that MUC16 is elevated and exhibits an apical staining pattern in LGSOC tumors. These findings deepen our molecular understanding of LGSOC and provide unique insights into the regulation of MUC16 in LGSOC tumors.

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Section: Discussionmentioning

confidence: 99%

Deep Quantitative Proteomics Identifies Conserved Proteome Alterations in Low and High-Grade Serous Ovarian Cancers

Tarney,

Mhawech-Fauceglia,

Ogata

et al. 2024

Preprint

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“…In 2004, Malpica et al [4] proposed a two-tier system to grade serous ovarian carcinoma into low or high grade. According to the binary system, the ovarian tumour is classified as a low grade if there is mild to moderate nuclear atypia and a mitotic index of up to 12 mitoses per 10 high-powered fields [10]. This system showed good reproducibility and prediction of the clinical outcome compared to the previously applied grading systems [4,11].…”

Section: Discussionmentioning

confidence: 99%

Prognostic factors and clinical hallmarks of low grade serous ovarian carcinoma: a single center study

2023

EJGO

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Ovarian cancer is the most fatal gynecologic malignancy. Low-grade type represents only 2-5% of all ovarian cancer pathological types. Its clinical characteristics, growth pattern, and response to treatment are distinct from high-grade serous ovarian carcinoma. In this study, we retrospectively evaluated the clinical features, prognostic factors, and survival of patients diagnosed with low-grade serous ovarian cancer from a tertiary cancer centre. This is a retrospective study where all patients diagnosed with lowgrade serous ovarian cancer (LGSOC) who presented to a tertiary cancer centre from July 2015 to August 2021 were included. Forty-two patients with low-grade ovarian serous carcinoma were enrolled. The mean age of the patients was 50.17 ± 10.91 years, while the mean Body Mass Index (BMI) was 32.96 ± 6.02 kg/m 2 . Primary optimal debulking was performed in 18 patients, while interval cytoreduction was done in 17 patients. Suboptimal debulking was performed in 5 patients. Neoadjuvant chemotherapy was administered in 19 patients (45.2%). The median overall survival of LGSOC patients was 95.58 (73.37-117.79) months while the median Progression free survival (PFS) was 56.54 (38.15-74.94) months. Primary cytoreductive surgery is still the cornerstone of the management of LGSOC patients. Neoadjuvant chemotherapy could be a predictor of worse progression-free survival in LGSOC patients presented with advanced disease stage.

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“…( Slomovitz et al, 2020 ) When limiting to only serous ovarian carcinomas, LGSOC still account for only 3–10 %. ( Slomovitz et al, 2020 , Zwimpfer et al, 2023 , Kaldawy et al, 2016 ) This percentage is likely closer to 3 % as the prevalence of LGSOC has been decreasing of late, in contrast to the increasing prevalence of the LGSOC precursor Serous Borderline Ovarian Tumors (SBOT). This is in part accounted by the improved surveillance and treatment trends of SBOT.…”

Section: Lgsoc Clinical Characteristicsmentioning

confidence: 99%

Durable response to BRAF inhibitor monotherapy in recurrent metastatic low grade serous ovarian cancer

Sama,

Rosqvist,

Savage

et al. 2024

Gynecologic Oncology Reports

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Low grade serous ovarian cancer – A rare disease with increasing therapeutic options

Cited by 11 publications

References 83 publications

Deep Quantitative Proteomics Identifies Conserved Proteome Alterations in Low and High-Grade Serous Ovarian Cancers

Deep Quantitative Proteomics Identifies Conserved Proteome Alterations in Low and High-Grade Serous Ovarian Cancers

Prognostic factors and clinical hallmarks of low grade serous ovarian carcinoma: a single center study

Durable response to BRAF inhibitor monotherapy in recurrent metastatic low grade serous ovarian cancer

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