Tumor Heterogeneity in Endometrial Carcinoma: Practical Consequences

Gatius, Sònia; Cuevas, Dolors; Fernández, Carlos; Roman‐Canal, Berta; Adamoli, Virginia; Piulats, Josep María; Eritja, Núria; Martı́n-Satué, Mireia; Moreno‐Bueno, Gema; Matías‐Guiu, Xavier

doi:10.1159/000475529

Cited by 26 publications

(21 citation statements)

References 17 publications

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“…High frequency of POLE, PTEN, CTNNB1, PIK3R1, ARID1A, KRAS mutations and microsatellite instability are found in type I tumors, whereas mutations in TP53 and FBXW7, and somatic copy number alterations are more frequently found in type II carcinomas (9, 10). Coenegrachts et al found that in majority of the cases, SC and EEC components in mixed EEC-SC exhibit distinct molecular characteristics, but have similar mutation profiles compared to SC and EEC cancers, respectively (11,12). In the present case with mixed histological components, frequently mutated genes in endometrioid tumors (PTEN, ARID1A, KRAS) and serous tumors (TP53, FBXW7) are all mutated.…”

Section: Discussionmentioning

confidence: 47%

Case Report: Double Germline Mutations in BRCA1 and MSH2 in a Patient With Mixed Serous-Endometrioid Endometrial Carcinoma

Zheng

Yuan

et al. 2020

Front. Med.

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Mixed serous-endometrioid endometrial carcinoma is a type of endometrial cancer with relatively low incidence. The genetic factors contributing to the tumorigenesis of mixed carcinoma remains to be explored. Here, we report the first identification of two germline mutations in BRCA1 and MSH2 in a woman with mixed serous papillary adenocarcinoma and endometrioid carcinoma. Immunohistochemistry analysis showed loss of MSH2 and MSH6 protein expression in the endometrioid component. The patient showed partial response to tislelizumab treatment following progression on chemotherapy. Two germline mutations in BRCA1 and MSH2 may collectively promote the tumorigenesis of uterine endometrium with two distinct histological components.

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Section: Discussionmentioning

confidence: 47%

Case Report: Double Germline Mutations in BRCA1 and MSH2 in a Patient With Mixed Serous-Endometrioid Endometrial Carcinoma

Zheng

Yuan

et al. 2020

Front. Med.

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“…EC is the most frequent of the malignant tumors of the female genital tract with an important intertumoral heterogeneity, depending on histological and molecular types, and also intratumoral, due to the different cell components within the same tumor [ 32 , 33 ]. The study of the protein expression profile of EC, including the study of ectonucleotidases, contributes to the improvement of the diagnosis and tumor staging and, in consequence, the clinical management of patients [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Endometrial MSC Marker Ectonucleoside Triphosphate Diphosphohydrolase-2 (NTPDase2/CD39L1) in Low- and High-Grade Endometrial Carcinomas: Loss of Stromal Expression in the Invasive Phenotypes

Rodríguez-Martínez

Trapero

Vidal

et al. 2021

JPM

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Ectonucleoside triphosphate diphosphohydrolase-2 (NTPDase2/CD39L1) has been described in human non-pathological endometrium in both epithelial and stromal components without changes along the cycle. It was identified as a stromal marker of basalis. In the present study, we aimed to evaluate NTPDase2 distribution, using immunolabeling and in situ enzyme activity approaches, in endometrial carcinoma (EC) at different tumor grades. NTPDase2 was present in tumor epithelial EC cells, as in the non-pathological endometria, but the expression underwent changes in subcellular distribution and also tended to decrease with the tumor grade. In stroma, NTPDase2 was identified exclusively at the tumor-myometrial junction but this expression was lost in tumors of invasive phenotype. We have also identified in EC samples the presence of the perivascular population of endometrial mesenchymal stem cells (eMSCs) positive for sushi domain containing 2 (SUSD2) and for NTPDase2, already described in non-tumoral endometrium. Our results point to NTPDase2 as a histopathological marker of tumor invasion in EC, with diagnostic relevance especially in cases of EC coexisting with other endometrial disorders, such as adenomyosis, which occasionally hampers the assessment of tumor invasion parameters.

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“…As all known, the substantial and disorder cell populations is an essential pathological characteristic of most malignant tumors, so the diffusion rate of water molecules is significantly slow in malignancies and they are always hyperintense on DWI. The heterogeneity is another important pathological feature of cancer, multi-region sequencings performed in many carcinomas including endometrial cancer, breast, lung, colorectal, and renal cancer have uncovered heterogeneity exists in all cancer types [22][23][24][25][26][27]. The heterogeneity may lead to different diffusion rate of water.…”

Section: Discussionmentioning

confidence: 99%

Can conventional DWI accurately assess the size of endometrial cancer?

Song

Shang

et al. 2019

Abdom Radiol

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Purpose To compare T2-weighted image (T2WI) and conventional Diffusion-weighted image (cDWI) of magnetic resonance imaging (MRI) for sensitivity of qualitative diagnosis and accuracy of tumor size (TS) measurement in endometrial cancer (EC). Meanwhile, the effect of the lesion size itself and tumor grade on the ability of T2WI and cDWI of TS assessment was explored. Ultimately, the reason of deviation on size evaluation was studied. Materials and methods 34 patients with EC were enrolled. They were all treated with radical hysterectomy and performed MR examinations before operation. Firstly, the sensitivity of T2WI alone and T2WI-DWI in qualitative diagnosis of EC were compared according to pathology. Secondly, TS on T2WI and cDWI described with longitudinal (LD) and horizontal diameter (HD) were compared to macroscopic surgical specimen (MSS) quantitatively in the entire lesions and the subgroup lesions which grouped by postoperative tumor size itself and tumor grade. Thirdly, the discrepancy of mean ADC values (ADC mean) and range ADC values (ADC range) between different zones of EC were explored. Results For qualitative diagnosis, the sensitivity of T2WI-DWI (97%) was higher than T2WI alone (85%) (p = 0.046).For TS estimation, no significant difference (PLD = 0.579; PHD = 0.261) was observed between T2WI (LDT2WI = 3.90 cm; HDT2WI = 2.88 cm) and MSS (LD = 4.00 cm; HD = 3.06 cm), whereas TS of cDWI (LDDWI = 3.01 cm; HDDWI = 2.54 cm) were smaller than MSS (PLD = 0.002; PHD = 0.002) in all lesions. In subgroup of tumor with G1 (grade 1) and small lesion (defined as maximum diameter < 3 cm), both T2WI and cDWI were not significantly different from MSS; In subgroup of tumor with G2 + 3 (grade 2 and grade 3) and big lesion (maximum diameter ≥ 3 cm), T2WI matched well with MSS still, but DWI lost accuracy significantly. The result of ADC values between different zones of tumor showed ADC mean of EC rose from central zone to peripheral zone of tumor gradually and ADC range widened gradually. Conclusion cDWI can detect EC very sensitively. The TS on cDWI was smaller than the fact for the ECs with G2/3 and big size. The TS of T2WI was in accordance with the actual size for all ECs. The heterogeneity may be responsible for the inaccuracy of cDWI.

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Tumor Heterogeneity in Endometrial Carcinoma: Practical Consequences

Cited by 26 publications

References 17 publications

Case Report: Double Germline Mutations in BRCA1 and MSH2 in a Patient With Mixed Serous-Endometrioid Endometrial Carcinoma

Case Report: Double Germline Mutations in BRCA1 and MSH2 in a Patient With Mixed Serous-Endometrioid Endometrial Carcinoma

Characterization of the Endometrial MSC Marker Ectonucleoside Triphosphate Diphosphohydrolase-2 (NTPDase2/CD39L1) in Low- and High-Grade Endometrial Carcinomas: Loss of Stromal Expression in the Invasive Phenotypes

Can conventional DWI accurately assess the size of endometrial cancer?

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