Hormone receptor expression and outcomes in low-grade serous ovarian carcinoma

Fernández, Marta Llauradó; Dawson, Amy; Kim, Hannah; Lam, Nicole Y.L.; Russell, Holly; Bruce, Maegan; Bittner, Madison; Hoenisch, Joshua; Scott, Stephanie; Talhouk, Aline; Chiu, Derek S.; Provencher, Diane; Nourmoussavi, Melica; DiMattia, Gabriel E.; Lee, Cheng‐Han; Gilks, C. Blake; Köbel, Martin; Carey, Mark

doi:10.1016/j.ygyno.2019.11.029

Cited by 29 publications

(21 citation statements)

References 33 publications

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“…Data from a large study integrating mutational data from targeted sequencing and IHC in LGSC suggest five molecular subtypes, and, listed in order of decreasing aggressiveness, they are CDKN2A IHC alteration > PR loss/high fraction of genome altered > MAPK pathway mutations ( KRAS , NRAS , BRAF ) ~ USP9X mutations ~ NSMP [ 98 ]. This could provide context for molecularly informed treatment decisions, such as CDK4/6 inhibitors for cases with CDKN2A loss versus hormonal therapy plus MEK inhibitors for MAPK-mutated cases with retained hormone receptor expression [ 63 , 90 , 99 , 100 , 101 ]. However, these findings require further validation in preclinical models and clinical trials.…”

Section: Molecular Subtypes Of Ovarian Carcinomasmentioning

confidence: 99%

The Evolution of Ovarian Carcinoma Subclassification

Köbel

Kang

2022

Cancers

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The phenotypically informed histotype classification remains the mainstay of ovarian carcinoma subclassification. Histotypes of ovarian epithelial neoplasms have evolved with each edition of the WHO Classification of Female Genital Tumours. The current fifth edition (2020) lists five principal histotypes: high-grade serous carcinoma (HGSC), low-grade serous carcinoma (LGSC), mucinous carcinoma (MC), endometrioid carcinoma (EC) and clear cell carcinoma (CCC). Since histotypes arise from different cells of origin, cell lineage-specific diagnostic immunohistochemical markers and histotype-specific oncogenic alterations can confirm the morphological diagnosis. A four-marker immunohistochemical panel (WT1/p53/napsin A/PR) can distinguish the five principal histotypes with high accuracy, and additional immunohistochemical markers can be used depending on the diagnostic considerations. Histotypes are further stratified into molecular subtypes and assessed with predictive biomarker tests. HGSCs have recently been subclassified based on mechanisms of chromosomal instability, mRNA expression profiles or individual candidate biomarkers. ECs are composed of the same molecular subtypes (POLE-mutated/mismatch repair-deficient/no specific molecular profile/p53-abnormal) with the same prognostic stratification as their endometrial counterparts. Although methylation analyses and gene expression and sequencing showed at least two clusters, the molecular subtypes of CCCs remain largely elusive to date. Mutational and immunohistochemical data on LGSC have suggested five molecular subtypes with prognostic differences. While our understanding of the molecular composition of ovarian carcinomas has significantly advanced and continues to evolve, the need for treatment options suitable for these alterations is becoming more obvious. Further preclinical studies using histotype-defined and molecular subtype-characterized model systems are needed to expand the therapeutic spectrum for women diagnosed with ovarian carcinomas.

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Section: Molecular Subtypes Of Ovarian Carcinomasmentioning

confidence: 99%

The Evolution of Ovarian Carcinoma Subclassification

Köbel

Kang

2022

Cancers

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“…Fernandez et al looked at the predictive value of the hormone receptors in 55 patients with advanced LGSC [ 64 ]. Both ER and PR Allred expression scores were significantly associated with OS outcomes in univariate analysis.…”

Section: Prognostic Considerationmentioning

confidence: 99%

Low-Grade Serous Carcinoma of the Ovary: The Current Status

et al. 2022

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Low-grade serous carcinoma (LGSC) of the ovary is a rare histological subtype of epithelial ovarian carcinoma. It has distinct clinical behavior and a specific molecular profile. Compared with high-grade serous carcinoma, this tumor presents at a younger age, has an indolent course, and is associated with prolonged survival. LGSC can arise de novo or originate following a serous borderline tumor (SBT). Pathological differentiation between LGSC and other ovarian carcinoma histological subtypes is fundamental. Several factors might influence the overall outcome, such as the age at diagnosis, current smoking, elevated body mass index, mutational status, hormonal receptors’ expression, and Ki-67 proliferation index. Surgery is the main treatment option in LGSC, and efforts must be maximized to achieve a microscopic residual in metastatic disease. Despite being relatively chemo-resistant, adjuvant platinum-based chemotherapy remains the standard of care in LGSC. Hormonal maintenance therapy after adjuvant chemotherapy results in improved outcomes. Treatment options for disease recurrence include secondary cytoreductive surgery, chemotherapy, hormonal therapy, targeted therapy, and clinical trials. Advancements in genomic studies and targeted therapies are expected to change the treatment landscape in LGSC.

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“…Utilizing a binary expression scoring system, LGSOC patients whose tumors were ER+/PR+ had a longer median time to progression than those with ER+/PR- tumors, suggesting that low PR expression appears to be associated with worse outcome independent of ER expression 13 . Strengthening this, in patients with advanced LGSOC, high levels of ERα expression as determined by Allred scoring is significantly associated with better overall survival outcomes, while low levels of PR expression are associated with a more aggressive disease course 15 .…”

Section: Introductionmentioning

confidence: 92%

“…Estrogen receptor (ER) expression is detected in the majority of LGSOC cases (50–90%) and progesterone receptor (PR) expression is less frequently observed (40–50% of cases) 7 , 11 – 14 . Hormone receptor expression appears to have both predictive and prognostic significance in this disease 7 , 13 , 15 . Utilizing a binary expression scoring system, LGSOC patients whose tumors were ER+/PR+ had a longer median time to progression than those with ER+/PR- tumors, suggesting that low PR expression appears to be associated with worse outcome independent of ER expression 13 .…”

Section: Introductionmentioning

confidence: 99%

Molecular characterization of low-grade serous ovarian carcinoma identifies genomic aberrations according to hormone receptor expression

et al. 2022

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Hormone receptor expression is a characteristic of low-grade serous ovarian carcinoma (LGSOC). Studies investigating estrogen receptor (ER) and progesterone receptor (PR) expression levels suggest its prognostic and predictive significance, although their associations with key molecular aberrations are not well understood. As such, we sought to describe the specific genomic profiles associated with different ER/PR expression patterns and survival outcomes in a cohort of patients with advanced disease. The study comprised fifty-five advanced-staged (III/IV) LGSOCs from the Canadian Ovarian Experimental Unified Resource (COEUR) for which targeted mutation sequencing, copy-number aberration, clinical and follow-up data were available. ER, PR, and p16 expression were assessed by immunohistochemistry. Tumors were divided into low and high ER/PR expression groups based on Allred scoring. Copy number analysis revealed that PR-low tumors (Allred score <2) had a higher fraction of the genome altered by copy number changes compared to PR-high tumors (p = 0.001), with cancer genes affected within specific loci linked to altered peptidyl-tyrosine kinase, MAP-kinase, and PI3-kinase signaling. Cox regression analysis showed that ER-high (p = 0.02), PR-high (p = 0.03), stage III disease (p = 0.02), low residual disease burden (p = 0.01) and normal p16 expression (p<0.001) were all significantly associated with improved overall survival. This study provides evidence that genomic aberrations are linked to ER/PR expression in primary LGSOC.

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Hormone receptor expression and outcomes in low-grade serous ovarian carcinoma

Cited by 29 publications

References 33 publications

The Evolution of Ovarian Carcinoma Subclassification

The Evolution of Ovarian Carcinoma Subclassification

Low-Grade Serous Carcinoma of the Ovary: The Current Status

Molecular characterization of low-grade serous ovarian carcinoma identifies genomic aberrations according to hormone receptor expression

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