Synchronous endometrioid endometrial and ovarian carcinomas are biologically related: A clinico‑pathological and molecular (next generation sequencing) study of 22�cases

Abstract

The criteria for distinction between independent primary tumors and metastasis from one site to the other in synchronous endometrioid endometrial and ovarian carcinoma (SEO) has been a matter of dispute for a long time. In our study we performed a comprehensive clinico-pathological and molecular analysis of 22 cases of SEO. Based on conventional clinico-pathological criteria the cases were classified as independent primary tumors (10 cases) and metastasis from one location to the other (12 cases). All tumors were analyzed by NGS with a panel of 73 genes (219 kbp). Clonal origin was confirmed in all cases by at least one shared mutation in PTEN, AKT1, PIK3CA, KRAS, TP53 and ARID1A. Two patients carried germline pathogenic mutation in cancer-predisposing genes BRCA1 or BARD1. Microsatellite instable phenotype was detected in 5/22 (22.7%) SEO, but in one case only in the endometrial tumor. In conclusion, our results showed that all 22 SEOs were clonally related, irrespectively of their clinico-pathological features. Even low grade and low stage tumors classified as independent primaries, according to the conventional morphological criteria, have a clonal origin. From the practical point of view, only the conventional morphological criteria should be used for the classification (staging) of these tumors. However, molecular profiling of these tumors may have prognostic and predictive meaning.

Clonal relationship and directionality of progression of synchronous endometrial and ovarian carcinomas in patients with DNA mismatch repair-deficiency associated syndromes

“…Combining our previously published synchronous EC/OC Lynch syndrome case, SV2 [ 12 ], with the analyses performed here, we report a 40% (2/5) rate of independent primary tumors versus metastatic lesions in patients with Lynch syndrome. This is in contrast to sporadic synchronous clinically independent ECs/OCs, which have been consistently shown to be clonally related and metastases from each other, as demonstrated by both our group and others [ 13 – 16 , 41 , 44 , 45 ].…”

Summary of BARD1 Mutations and Precise Estimation of Breast and Ovarian Cancer Risks Associated with the Mutations

“…A total of 265 studies were further assessed by the full-text review, of which 145 studies not meeting the criteria (described in the Methods section and Figure S1 ) were excluded. Finally, for the analysis, we included 123 studies: 120 studies from the PubMed search and 3 hand-searched studies [ 15 , 16 , 18 , 19 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , …”

Synchronous quadruple primary malignancies of the cervix, endometrium, ovary, and stomach in a single patient: A case report and review of literature

“…In ovarian tumors the criteria include the the presence of endometriosis, size and laterality of the tumor, surface implants, hilar location, lympho vascular space invasion, and multinodularity. SEOC is ordinarily more likely to be stage I disease with endometrioid histology[6,7]. In the present case we ultimately considered both to be primary carcinomas in the uterus corpus and ovary.…”

“…As well as congenital genetic mutations, somatically acquired genetic abnormalities such as punctiform mutations, loss of heterozygosity and microsatellite instability can also contribute to carcinogenesis[2]. Hájková et al[7] conducted comprehensive molecular analysis in 22 SEOC patients and reported that clonal origin was confirmed in all of them by way of at least one shared mutation in PTEN, AKT1, PIK3CA, KRAS, TP53, or ARID1A. Microsatellite instability phenotypes were detected in 5/22 (22.7%) SEOC of the patients.…”