Converging endometrial and ovarian tumorigenesis in Lynch syndrome: Shared origin of synchronous carcinomas

Niskakoski, Anni; Pasanen, Annukka; Porkka, Noora; Eldfors, Samuli; Lassus, Heini; Renkonen–Sinisalo, Laura; Kaur, Sippy; Mecklin∥, Jukka–Pekka; Bützow, Ralf; Peltomäki, Païvi

doi:10.1016/j.ygyno.2018.04.566

Cited by 36 publications

(35 citation statements)

References 32 publications

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“…This is the largest series so far, confirming the clonal relationship between both carcinomas in concurrent cases diagnosed as SEOs, implying these carcinomas actually represent (pseudo)metastatic disease, rather than two independently evolved carcinomas . The mechanisms underlying the spread from one anatomic site to another, without carrying a dismal prognosis are not fully understood.…”

Section: Discussionmentioning

confidence: 95%

Molecular profiling identifies synchronous endometrial and ovarian cancers as metastatic endometrial cancer with favorable clinical outcome

Reijnen

Küsters‐Vandevelde

Ligtenberg

et al. 2020

Intl Journal of Cancer

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Synchronous primary endometrial and ovarian cancers (SEOs) represent 10% of all endometrial and ovarian cancers and are assumed to develop as independent entities. We investigated the clonal relationship between endometrial and ovarian carcinomas in a large cohort classified as SEOs or metastatic disease (MD). The molecular profiles were compared to The Cancer Genome Atlas (TCGA) data to explore primary origin. Subsequently, the molecular profiles were correlated with clinical outcome. To this extent, a retrospective multicenter study was performed comparing patients with SEOs (n = 50), endometrial cancer with synchronous ovarian metastasis (n = 19) and ovarian cancer with synchronous endometrial metastasis (n = 20). Targeted nextgeneration sequencing was used, and a clonality index was calculated. Subsequently, cases were classified as POLE mutated, mismatch repair deficient (MMR-D), TP53-wild-type or TP53-mutated. In 92% of SEOs (46/50), the endometrial and concurrent ovarian carcinoma shared at least one somatic mutation, with a clonality index above 0.95, supporting a clonal origin. The SEO molecular profiles showed striking similarities with the TCGA endometrial carcinoma set. SEOs behaved distinctly different from metastatic disease, with a superior outcome compared to endometrial MD cases (p < 0.001) and ovarian MD cases (p < 0.001). Classification according to the TCGA identified four groups with different clinical outcomes. TP53 mutations and extra-uteroovarian disease were independent predictors for poor clinical outcome. Concluding, SEOs were clonally related in an overwhelming majority of cases and showed a favorable prognosis. Their molecular profile implied a primary endometrial origin. TP53 mutation and extra-utero-ovarian disease were independent predictors for outcome, and may impact adjuvant systemic treatment planning.Additional Supporting Information may be found in the online version of this article.

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Section: Discussionmentioning

confidence: 95%

Molecular profiling identifies synchronous endometrial and ovarian cancers as metastatic endometrial cancer with favorable clinical outcome

Reijnen

Küsters‐Vandevelde

Ligtenberg

et al. 2020

Intl Journal of Cancer

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“…). One study was excluded because it assessed the same sample as another included study . The total sample size was 1429, including 467 EHs.…”

Section: Resultsmentioning

confidence: 99%

Diagnostic and prognostic value of ARID1A in endometrial hyperplasia: a novel marker of occult cancer

Raffone

Travaglino

Saccone

et al. 2019

APMIS

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Raffone A, Travaglino A, Saccone G, Cieri M, Mascolo M, Mollo A, Insabato L, Zullo F. Diagnostic and prognostic value of ARID1A in endometrial hyperplasia: a novel marker of occult cancer. APMIS 2019; 127: 597-606.AT-rich interaction domain 1A (ARID1A) is a tumor suppressor protein involved in endometrioid carcinogenesis. The expression of ARID1A may be lost in the premalignant phase. Our aim was to assess ARID1A as: (i) diagnostic marker to differentiate premalignant endometrial hyperplasia (EH) form benign EH; (ii) prognostic marker for the risk of occult cancer in premalignant EH. A systematic review and meta-analysis were performed by searching electronic databases from their inception to October 2018 for all studies assessing ARID1A in EH by immunohistochemistry. Sensitivity, specificity, positive and negative likelihood ratios (LR+ and LRÀ), and diagnostic odds ratio (DOR) were calculated for both diagnostic and prognostic accuracy. LR+ > 5, LRÀ < 0.2, DOR > 25 defined good accuracy; LR+ > 10, LRÀ < 0.1, DOR > 100 defined excellent accuracy. Seven studies with 467 EH were included. As diagnostic marker, ARID1A showed sensitivity = 0.12, specificity = 0.99, LR+ = 4.34, LRÀ = 0.85, DOR = 5.12. As prognostic marker for occult cancer, ARID1A showed sensitivity = 0.33, specificity = 0.99, LR+ = 20.70, LRÀ = 0.49, DOR = 49.59. In conclusion, ARID1A loss is highly specific, but little accurate as diagnostic marker of premalignant EH. Instead, ARID1A loss in premalignant EH is an accurate and almost perfectly specific prognostic marker for coexistent cancer.

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Section: Simultane Endometriumund Ovarialkarzinome (Seoc)unclassified

“…Bei LS-Patientinnen mit primär diagnostiziertem EC oder OC werden in 20-25 % simultane EC plus OC (SEOC) gefunden [14,20,22]. Bei spontanen EC oder OC wird eine SEOC-Häufigkeit von 10 % geschätzt [20,22]. Nach neuesten Erkenntnissen handelt es sich meist nicht um synchrone Karzinome verschiedener Organe, sondern um ein metastatisches Geschehen, wobei der Primarius am ehesten dem Endometrium zuzuordnen ist [20,22].…”

Section: Simultane Endometriumund Ovarialkarzinome (Seoc)unclassified

Das Lynch-Syndrom als bedeutendes erbliches Tumorsyndrom

Emons¹

2020

Frauenheilkunde up2date

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Converging endometrial and ovarian tumorigenesis in Lynch syndrome: Shared origin of synchronous carcinomas

Cited by 36 publications

References 32 publications

Molecular profiling identifies synchronous endometrial and ovarian cancers as metastatic endometrial cancer with favorable clinical outcome

Molecular profiling identifies synchronous endometrial and ovarian cancers as metastatic endometrial cancer with favorable clinical outcome

Diagnostic and prognostic value of ARID1A in endometrial hyperplasia: a novel marker of occult cancer

Das Lynch-Syndrom als bedeutendes erbliches Tumorsyndrom

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