DNA Ploidy Heterogeneity in Endometrial Carcinoma

Pradhan, Manohar; Abeler, Vera M.; Davidson, Ben; Kildal, Wanja; Nybøen, Åsmund; Tropé, Claes G.; Risberg, Bjørn; Danielsen, Håvard E.

doi:10.1097/pgp.0b013e3181e2e8ee

Cited by 9 publications

(6 citation statements)

References 25 publications

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“…Subsequently, after terminating the study, we found that the DNA ploidy results differed in the specimens in approximately one-fourth of the cases [30]. We found that DNA ploidy results from hysterectomy specimen provided better prognostic information compared with curettage specimen.…”

Section: Discussionmentioning

confidence: 99%

Prognostic importance of DNA ploidy and DNA index in stage I and II endometrioid adenocarcinoma of the endometrium

et al. 2012

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Background:We evaluated the prognostic importance of DNA ploidy in stage I and II endometrioid adenocarcinoma (EAC) of the endometrium with a focus on DNA index.Patients and methods:High-resolution DNA ploidy analysis was carried out in tumor material from 937 consecutive patients with International Federation of Gynecology and Obstetrics (FIGO) stage I and II EAC of the endometrium.Results:Patients with diploid (N = 728), aneuploid tumor with DNA index ≤1.20 (N = 118), aneuploid tumors with DNA index >1.20 (N = 39) and tetraploid tumor (N = 52) had 5-year recurrence rates 8%, 14%, 20% and 12%, respectively. Patients with aneuploid tumor with DNA index >1.20 had a poorer 5-year progression-free survival (67%) and overall survival (72%) compared with the patients with aneuploid tumor with DNA index ≤1.20 (81% and 89%, respectively). Aneuploid tumors with DNA index ≤1.20 relapsed mainly in the vagina and pelvis, whereas aneuploid tumors with DNA index >1.20 relapsed predominantly outside pelvis.Conclusions:The recurrence risk for the patients with aneuploid tumor is higher than the patients with diploid tumor in EAC of the endometrium. Based on DNA index with cut-off 1.20, aneuploid tumors can be separated into two subgroups with different recurrence pattern and survival.

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Section: Discussionmentioning

confidence: 99%

Prognostic importance of DNA ploidy and DNA index in stage I and II endometrioid adenocarcinoma of the endometrium

et al. 2012

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“…In our study, DNA ploidy was analyzed either preoperatively or on hysterectomy specimens and with different methods (see Methods). However, the concordance between DNA ploidy on curettage and hysterectomy specimens is considered to be fairly high . The majority of DNA analyses were performed by flow cytometry on deparaffinized tumor samples.…”

Section: Discussionmentioning

confidence: 99%

Risk factors for lymph node metastases in women with endometrial cancer: A population‐based, nation‐wide register study—On behalf of the Swedish Gynecological Cancer Group

Stålberg

Kjølhede

Bjurberg

et al. 2017

Intl Journal of Cancer

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Risk factors for lymph node metastases in women with endometrial cancerA population-based, nation-wide register study-On behalf of the Swedish Gynecological Cancer Group Stålberg, Karin; Kjølhede, P.; Bjurberg, M.; Borgfeldt, C.; Dahm-Kähler, Pernilla; Falconer, Henrik; Holmberg, E.; Staf, Christian; Tholander, Bengt; Åvall Lundqvist, Elisabeth; Rosenberg, P; Högberg, T. Link to publication Citation for published version (APA): Stålberg, K., Kjølhede, P., Bjurberg, M., Borgfeldt, C., Dahm-Kähler, P., Falconer, H., ... Högberg, T. (2017). Risk factors for lymph node metastases in women with endometrial cancer: A population-based, nation-wide register study-On behalf of the Swedish Gynecological Cancer Group. International Journal of Cancer, 140(12), 2693-2700. https://doi.org/10.1002/ijc.30707General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. AbstractThe role of lymphadenectomy in the management of early endometrial cancer is still controversial. In the recent ESMO-ESGO-ESTRO guidelines, lymphadenectomy is recommended for patients with endometrioid adenocarcinoma grade 3 with deep myometrial invasion, but complete agreement was not achieved. In Sweden, DNA aneuploidy has been included as a high-risk factor. The aim of our study was to evaluate the impact of tumor histology, FIGO grade, DNA ploidy and myometrial invasion (MI) on occurrence of lymph node metastasis (LNM) in patients with endometrial cancer.The study design is a retrospective cohort study based on prospectively recorded register data. This population-based, nation-wide study in women with endometrial cancer confirms a strong association between MI≥50%, non-endometrioid histology, and FIGO grade 3, respectively and LNM. DNA ploidy should not be included in the pre-operative decision making of removing nodes or not.

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“…However, these somatic copy number alterations may not be homogeneous across the tumor as demonstrated by intratumoral heterogeneity of DNA ploidy, a surrogate for copy number alterations. 34 Consequently, nuclear grade may also vary.…”

Section: Serous Molecular Type With Areas Resembling Other Endometriamentioning

confidence: 99%

Molecular Analysis of Mixed Endometrial Carcinomas Shows Clonality in Most Cases

Köbel

Meng

Hoang

et al. 2016

American Journal of Surgical Pathology

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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).

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DNA Ploidy Heterogeneity in Endometrial Carcinoma

Cited by 9 publications

References 25 publications

Prognostic importance of DNA ploidy and DNA index in stage I and II endometrioid adenocarcinoma of the endometrium

Prognostic importance of DNA ploidy and DNA index in stage I and II endometrioid adenocarcinoma of the endometrium

Risk factors for lymph node metastases in women with endometrial cancer: A population‐based, nation‐wide register study—On behalf of the Swedish Gynecological Cancer Group

Molecular Analysis of Mixed Endometrial Carcinomas Shows Clonality in Most Cases

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