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Page 12 of 18 Malentacchi et al. J Cancer Metastasis Treat 2020;6:34 I http://dx.doi.org/10.20517/2394-4722.2020.34

LGALS3BP was significantly enriched in circulating EVs from an EC patient cohort with a high risk of
[81]
recurrence .

Platelet
Platelets contain many different RNA species including miRNAs, circRNAs, and mRNAs that are altered in
[85]
cancer. No studies regarding platelets have been performed on EC .

URINE
miRNA
The improvement of high throughput technologies such as NGS and qPCR allowed the evaluation of
[86]
specific biomarkers, such as cell-free miRNAs, in urine and methylation profile of cell free tumor .
[87]
A study reported a specific downregulation of miR-106b, as well as in serum and plasma samples, in
[24]
comparison with healthy donors .
Recently, Ye reported the identification of several miRNA involved in Grade 3 EC (miR-9, miR-92a, miR-99a,
miR-100, miR-199b, miR-1228, miR-9, miR-1228, miR-9, miR-92a, miR-21, miR-222, miR-223, miR-186
[88]
and miR-204, miR-203, miR-21, miR-887-5p, miR-106b, and miR-200c-3p) .

UTERINE/PERITONEAL LAVAGE CYTOLOGY
Surgical staging of gynecologic neoplasms, mainly in ovarian cancer, include the collection of peritoneal
washings coming from the abdomen and pelvis. The aim of taking peritoneal washings is to identify
occult disease. Peritoneal cytology is supposed to add information on the spread of microscopic peritoneal
disease. However, the peritoneal washing cytology examination may give false positivity in benign diseases
and false negativity in the early stages.

Less is known about the prognostic impact of peritoneal cytology in EC and published data show
inconsistent results, mainly in relation to the prognostic importance of positive cytology to predict relapse
[89]
or metastasis . Recently, the use of cytology PAP-test, usually performed for cervical cancer evaluation,
[90]
has been proposed to analyzed endometrial cancer, in particular the liquid cytology approach (LC) . This
procedure is worth mentioning in this overview, even if this procedure is not a true LB but a procedure
in between biopsy and LB, mainly because the collection procedure is minimally invasive and allows
collecting tumor cells derived from gynecological districts. After uterine lavage with saline solution, the
collection of cancer cells can allow identifying genetic variations related to endometrial cancer by the
washing of the uterine cavity. The data suggest that LC is a feasible and reproducible adjuvant method
for screening endometrial lesions and in combination with classical biopsy can improve the diagnostic
accuracy of endometrial lesions [90-94] .

To identify other biomarkers for implementing cytology, recent studies demonstrated the role of IL-11
protein in uterine fluids related with the amount in endometrial tumor epithelial cells in women with grade
[95]
1 EC . In a case report, in cells deriving from uterine lavage, mutations on PTEN, TP53, PIK3CA, PIK3R1,
KRAS, CTNNB1, FGFR2, RNF43, PPP2R1A, POLE, APC, and FBXW7 were observed; these are genes that
are some of the most frequently mutated in EC [24,96-98] . In addition, exosome contents, mainly referring to
miRNAs, showed that 114 miRNAs (by mRNA array) were significantly dysregulated in EC patients. Eight
miRNAs (miRNA-383-5p, miRNA-10b-5p, miRNA-34c-3p, miRNA-449b-5p, miRNA-34c-5p, miRNA-
200b-3p, miRNA-2110, and miRNA-34b-3p) demonstrated classification performance according to the area
[99]
under the receiver operating characteristic curve .