Defining a mutational signature for endometrial cancer screening and early detection

Costas, Laura; Palomero, Luís; Benavente, Yolanda; Guardiola, Magdalena; Frias-Gomez, Jon; Pavón, Miquel Ángel; Climent, Maite; Martínez, José Manuel; Barahona, Marc; Salinas, Mónica; Pineda, Marta; Bianchi, Ilaria; Reventós, Jaume; Capellà, Gabriel; Díaz, Mireia; Vidal, August; Piulats, Josep María; Ponce, Jordi; Brunet, Joan; Bosch, F. Xavier; Matías‐Guiu, Xavier; Alemany, Laia; Sanjosé, Sílvia de; Aytés, Álvaro

doi:10.1016/j.canep.2019.06.003

Cited by 8 publications

(5 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Briefly, DNA mutation analysis was performed for five genes ( PTEN , TP53 , PIK3CA , ARID1A , and CTNNB1 ) that led to the highest sensitivity of identifying cancers (ie, 92.9%) in The Cancer Genome Atlas data set, as previously described. 25…”

Section: Methodsmentioning

confidence: 99%

A Simple Cervicovaginal Epigenetic Test for Screening and Rapid Triage of Women With Suspected Endometrial Cancer: Validation in Several Cohort and Case/Control Sets

Herzog

Marín

Jones

et al. 2022

JCO

Self Cite

View full text Add to dashboard Cite

PURPOSE Endometrial cancer (EC) incidence has been rising over the past 10 years. Delays in diagnosis reduce survival and necessitate more aggressive treatment. We aimed to develop and validate a simple, noninvasive, and reliable triage test for EC to reduce the number of invasive diagnostic procedures and improve patient survival. METHODS We developed a test to screen and triage women with suspected EC using 726 cervical smear samples from women with and without EC, and validated the test in 562 cervicovaginal samples using three different collection methods (cervical smear: n = 248; vaginal swab: n = 63; and self-collection: n = 251) and four different settings (case/control: n = 388; cohort of women presenting with postmenopausal bleeding: n = 63; a cohort of high-risk women with Lynch syndrome: n = 25; and a nested case/control setting from a screening cohort and samples taken up to 3 years before EC diagnosis: n = 86). RESULTS We describe the Women's cancer risk IDentification – quantitative polymerase chain reaction test for Endometrial Cancer (WID-qEC), a three-marker test that evaluates DNA methylation in gene regions of GYPC and ZSCAN12. In cervical, self-collected, and vaginal swab samples derived from symptomatic patients, it detected EC with sensitivities of 97.2% (95% CI, 90.2 to 99.7), 90.1% (83.6 to 94.6), and 100% (63.1 to 100), respectively, and specificities of 75.8% (63.6 to 85.5), 86.7% (79.3 to 92.2), and 89.1% (77.8 to 95.9), respectively. The WID-qEC identified 90.9% (95% CI, 70.8 to 98.9) of EC cases in samples predating diagnosis up to 1 year. Test performance was similar across menopausal status, age, stage, grade, ethnicity, and histology. CONCLUSION The WID-qEC is a noninvasive reliable test for triage of women with symptoms suggestive of ECs. Because of the potential for self-collection, it could improve early diagnosis and reduce the reliance for in-person visits.

show abstract

Section: Methodsmentioning

confidence: 99%

A Simple Cervicovaginal Epigenetic Test for Screening and Rapid Triage of Women With Suspected Endometrial Cancer: Validation in Several Cohort and Case/Control Sets

Herzog

Marín

Jones

et al. 2022

JCO

Self Cite

View full text Add to dashboard Cite

show abstract

“…Because CA-125 levels may be elevated in numerous benign conditions, such as adenomyosis, uterine fibroids, and endometriosis, the determination of CA-125 alone seems to be insufficient. In turn, Costas et al [ 18 ] developed an algorithm to identify patients with EC using genetic molecular tests. Targeting the 50 most representative point mutations resulted in a sensitivity of over 80%, although at a high cost and requiring a technology able to sequence large DNA regions [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…In turn, Costas et al [ 18 ] developed an algorithm to identify patients with EC using genetic molecular tests. Targeting the 50 most representative point mutations resulted in a sensitivity of over 80%, although at a high cost and requiring a technology able to sequence large DNA regions [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Expression of E-Cadherin and N-Cadherin in the Endocervix as a Predictive Factor in Patients with Endometrial Cancer

Frąszczak,

Barczyński,

Tylus

et al. 2024

IJMS

View full text Add to dashboard Cite

Endometrial cancer (EC) is the most common gynecological malignancy. This study aimed to evaluate the expression of E-cadherin and N-cadherin in primary endometrial lesions and the endocervix in patients with EC to identify noninvasive predictive factors. In this single-center retrospective study, data on 101 patients who underwent surgery for EC were collected. The immunohistochemical expression of E-cadherin and N-cadherin was assessed depending on the tumor grade, location, and cell differentiation. Correlations between E-cadherin and N-cadherin levels in the endocervix and the primary tumor were determined. The degree of histological tumor differentiation significantly affected E-cadherin expression (p = 0.04) but had no impact on N-cadherin levels. In type II EC, the expression of both cadherins in the tumor tissue differed from their endocervical levels. The expression of E-cadherin differed significantly between the endocervix (p < 0.001) and the tumor (p = 0.001), depending on the type of EC. The expression of E-cadherin was related to the N-cadherin level only in the endocervix in patients with type II EC (p = 0.02). E-cadherin and N-cadherin were expressed in the endocervix in patients with EC. The expression of cadherins, determined during cervical cytology, may be a valuable clinical marker of EC.

show abstract

“…We used an NGS custom panel targeting exonic regions and intron-exon boundaries of 47 genes recurrently mutated in endometrial cancer, based on an analyses of The Cancer Genome Atlas (TCGA) dataset, 31 to evaluate the variants in cervicovaginal samples and molecularly classify cancer cases (ClassEC test). The panel consisted of the following genes: POLE, TP53, PTEN, PIK3CA, PIK3R1, ARID1A, KRAS, CTNNB1, FBXW7, KMT2D, CHD4, CSMD3, KCNG4, NIPBL, PPP2R1A, RPL22, SETD1B, RNF43, JAK1, FGFR2, BCOR, DOCK3, SPOP, SOX17, ACVR2A, CTCF, SOS1, LZTR1, AP4E1, ARHGAP35, MYOM1, BAX, WWC3, SOX5, RACGAP1, TNRC6A, HOXD8, KRIT1, PAX2, AKT1, APC, BRAF, CDKN2A, EGFR, MAPK1, NRAS, and SPEN.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of somatic mutations in cervicovaginal samples as a non-invasive method for the detection and molecular classification of endometrial cancer

Pelegrina,

Paytubi,

Marin

et al. 2023

eBioMedicine

Self Cite

View full text Add to dashboard Cite

Defining a mutational signature for endometrial cancer screening and early detection

Cited by 8 publications

References 18 publications

A Simple Cervicovaginal Epigenetic Test for Screening and Rapid Triage of Women With Suspected Endometrial Cancer: Validation in Several Cohort and Case/Control Sets

A Simple Cervicovaginal Epigenetic Test for Screening and Rapid Triage of Women With Suspected Endometrial Cancer: Validation in Several Cohort and Case/Control Sets

Expression of E-Cadherin and N-Cadherin in the Endocervix as a Predictive Factor in Patients with Endometrial Cancer

Evaluation of somatic mutations in cervicovaginal samples as a non-invasive method for the detection and molecular classification of endometrial cancer

Contact Info

Product

Resources

About