Pure Compared With Mixed Serous Endometrial Carcinoma

Roelofsen, Thijs; Ham, Maaike A.P.C. van; Tilburg, Johanna M. Wiersma van; Zomer, Saskia F.; Bol, Mijke; Massuger, Leon F.A.G.; Bulten, Johan

doi:10.1097/aog.0b013e318273732e

Cited by 31 publications

(22 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, diagnosis of cases with a high-grade component of sometimes less than 10% is particularly challenging, and there are currently no biomarkers that can be used to accurately identify MT-ECs. Clinical studies of prognoses of patients with MT-ECs have yielded contradictory results: some report that MT-ECs with a serous component have the same prognoses as pure USC cases [ 2 , 19 ], whereas other studies suggest MT-ECs have more favorable outcomes than their pure serous counterparts [ 20 ]. Moreover the biology of MT-ECs is poorly understood, and it is not known whether these tumors are truly mixed, or if the predominant histology represented indicates the true histology and etiology of the tumor.…”

Section: Discussionmentioning

confidence: 99%

Molecular Analysis of Mixed Endometrioid and Serous Adenocarcinoma of the Endometrium

et al. 2015

View full text Add to dashboard Cite

BackgroundThe molecular biology and cellular origins of mixed type endometrial carcinomas (MT-ECs) are poorly understood, and a Type II component of 10 percent or less may confer poorer prognoses.Methodology/Principal FindingsWe studied 10 cases of MT-EC (containing endometrioid and serous differentiation), 5 pure low-grade endometrioid adenocarcinoma (EAC) and 5 pure uterine serous carcinoma (USC). Endometrioid and serous components of the MT-ECs were macrodissected and the expression of 60 candidate genes compared between MT-EC, pure USC and pure EAC. We found that four genes were differentially expressed when MT-ECs were compared to pure low-grade EAC: CDKN2A (P = 0.006), H19 (P = 0.010), HOMER2 (P = 0.009) and TNNT1 (P = 0.006). Also while we found that even though MT-ECs closely resembled the molecular profiles of pure USCs, they also exhibit lower expression of PAX8 compared to all pure cases combined (P = 0.035).ConclusionOur data suggest that MT-EC exhibits the closest molecular and epidemiological similarities to pure USC and supports clinical observations that suggest patients with MT-EC should receive the same treatment as patients with pure serous carcinoma. Novel specific markers of MT-EC could be of diagnostic utility and could represent novel therapeutic targets in the future.

show abstract

Section: Discussionmentioning

confidence: 99%

Molecular Analysis of Mixed Endometrioid and Serous Adenocarcinoma of the Endometrium

et al. 2015

View full text Add to dashboard Cite

show abstract

“…24, 31, 32 We therefore believe based on current evidence that it is important not to mistaken these tumors as serous carcinoma or mixed carcinoma with serous component because of their better prognosis compared to typical TP53 -mutated pure serous carcinoma. 6 …”

Section: Hypermutated/ultramutated Molecular Type With Mmr-deficiencymentioning

confidence: 99%

“…3-5 Excluding mixed endometrioid and undifferentiated carcinoma (also referred to as dedifferentiated carcinoma), the most common scenario for mixed endometrial carcinoma based on the literature is mixed endometrioid and serous carcinoma, followed by mixed endometrioid and clear cell carcinoma. 2-6 …”

Section: Introductionmentioning

confidence: 99%

Molecular Analysis of Mixed Endometrial Carcinomas Shows Clonality in Most Cases

Köbel

Meng

Hoang

et al. 2016

American Journal of Surgical Pathology

View full text Add to dashboard Cite

Mixed endometrial carcinoma refers to a tumor that is comprised of two or more distinct histotypes. We studied 18 mixed-type endometrial carcinomas - 11 mixed serous and low-grade endometrioid carcinomas (SC/EC), 5 mixed clear cell and low-grade endometrioid carcinomas (CCC/EC), and 2 mixed clear cell and serous carcinoma (CCC/SC), using targeted next generation sequencing and immunohistochemistry to compare the molecular profiles of the different histotypes present in each case. In 16 of 18 cases there was molecular evidence that both components shared a clonal origin. Eight cases (6 EC/SC, 1 EC/CCC and 1 SC/CCC) showed a serous carcinoma molecular profile that was the same in both components. Five cases (3 CCC/EC and 2 SC/EC) showed a shared endometrioid molecular profile and identical mismatch repair protein (MMR) deficiency in both components. A single SC/EC case harbored the same POLE exonuclease domain mutation in both components. One SC/CCC and one EC/CCC case showed both shared and unique molecular features in the two histotype components, suggesting early molecular divergence from a common clonal origin. In two cases, there were no shared molecular features and these appear to be biologically unrelated synchronous tumors. Overall, these results show that the different histologic components in mixed endometrial carcinomas typically share the same molecular aberrations. Mixed endometrial carcinomas most commonly occur through morphological mimicry, whereby tumors with serous-type molecular profile show morphological features of endometrioid or clear cell carcinoma, or through underlying deficiency in DNA nucleotide repair, with resulting rapid accrual of mutations and intratumoral phenotypic heterogeneity. Less commonly, mixed endometrial carcinomas are the result of early molecular divergence from a common progenitor clone or are synchronous biologically unrelated tumors (collision tumors).

show abstract

“…Mixed endometrioid-serous carcinoma and ambiguous tumors SC usually occurs in pure form; however, occasionally, it may coexist with EEC. [45][46][47] It has been suggested that the serous component may arise as a result of progression of the endometrioid elements. When the second of these components is present in at least 5% of the tumor, the designation of mixed endometrial carcinoma is used, being mixed endometrioid and SC (mixed EEC-SC) the most frequent combination.…”

Section: Low-grade Eecmentioning

confidence: 99%

“…When the second of these components is present in at least 5% of the tumor, the designation of mixed endometrial carcinoma is used, being mixed endometrioid and SC (mixed EEC-SC) the most frequent combination. The correct diagnosis of the second component is crucial to determine treatment options and outcome for these patients, 45,46,48 as it has been suggested that the presence of as little as 10% of a type-II component could adversely affect patient's outcome. There is some interobserver variation in histological typing in endometrial carcinoma.…”

Section: Low-grade Eecmentioning

confidence: 99%