Gynecological examination is usually completed by transvaginal sonography (TVS), which is usually the first imaging method [1].

When TVS is performed by an experienced examiner, it is not always necessary to perform additional investigations to assess the local extent of the disease when it comes to endometrial cancer, such as magnetic resonance imaging (MRI) and computed tomography (CT) [1, 2].

On TVS, myometrial invasion (MI) appears as iso-hyperechoic tissue relative to the surrounding myometrium. Although MI is often well-diagnosed, it can sometimes only be suspected based on the irregular appearance of the endomyometrial zone [1, 3].

Both objective and subjective TVS methods are used to assess the degree of MI [1]. Objective evaluation is done using the Gordon and Karlsson ratio or method [2, 3, 4, 5].

Subjective TVS assessment of MI (50% or $>$50%) may be as good or better than any objective measurement technique with a sensitivity of 77% and specificity of 81% [1, 5].

Alcázar et al. [4] investigated that the sensitivity and specificity of TVS in detecting deep MI in endometrial cancer (EC) is 82% and 81%.

Currently, TVS represents one of the best possible inexpensive recording techniques. In addition to wide availability and cost-effectiveness, further advantages are that with this technique the examination can be performed quickly, reliably, safely and without additional stress for the patient. The reliability of the method depends on the quality of the ultrasound device, as well as the experience of the doctor performing the examination. The presence of adenomyosis, leiomyoma or endometrial polyps can be an aggravating circumstance in the assessment of MI [5, 6].

The sensitivity, specificity, positive and negative predictive value and diagnostic accuracy achieved in the study by Miklos et al. [6] further justify the integration of TVS into the standard preoperative protocol for EC patients. The rationale is that TVS provides information on the basis of which there is a possibility of making the correct decision about what type of surgical treatment should be performed, thus increasing the survival rates of patients and the overall therapeutic benefit [5, 6].

The aim of this study is to examine the ultrasound characteristics of endometrial cancer in two groups of patients; with myometrial invasion less and greater than 50%.

The basic demographic and clinical characteristics of study participants are shown in Table 1.

The average degrees of MI in EC for the gold standard - pathohistological method, are shown in Table 2.

The three EC dimensions obtained by TVS (expressed in centimeters) are statistically significantly higher in patients with MI $>$50% (Table 3).

The frequency of AP diameter of EC, measured by TVS, of less and greater than 2 centimeters in the two examined groups is shown in Table 4. The frequency of AP diameter of EC greater than 2 cm was statistically significantly higher in the group of subjects with MI $>$50%. (Z = 4.396; p 0.00001) (Table 4).

The volume of EC on TVS expressed in milliliters in the two examined groups is shown in Table 5. The volume of EC in the group of patients with MI $>$50% is statistically significantly higher (Mann Whitney; Z = –3.79; p 0.00014), with a difference of 10.48 milliliters compared to the group of subjects with MI 50% (Table 5).

The distance of the EC from the serosa—the minimum tumor-free zone expressed in centimeters, measured by TVS, is shown in Table 6. The difference in the average distance of the EC from the serosa is 1.1 cm between the two examined groups and is statistically significant (Mann Whitney; Z = 2.05; p = 0.0394) (Table 6).

The concordance of the diagnosis of MI over 50% by means of TVS method was then evaluated against the gold standard - the finding obtained by PHD diagnostics.

When it came to the subjective TVS method, a tabular representation of the concordance of the findings is given in Table 7. The kappa concordance coefficient for the subjective TVS method versus the PHD finding was statistically significant (p 0.001), and was kappa = 0.72. Analysis of the diagnostic accuracy showed that the subjective TVS method compared to the gold standard in the diagnosis of MI $>$50% has a good diagnostic value (Table 6). According to the subjective method of TVS, the degree of MI was overestimated in 5.9% of respondents, underestimated in 23.1%.

Our prospective cohort study, in which we analyzed the ultrasound characteristics of endometrial cancer and the degree of myometrial invasion, showed that there was no statistically significant difference in the assessment of the degree of MI between the subjective TVS method and histopathology as gold standard. Analysis of the diagnostic accuracy showed that the subjective TVS method compared to the gold standard in the diagnosis of MI $>$50% has a good diagnostic value.

Ultrasound parameters; three dimensions of EC obtained by TVS, AP diameter of EC greater than 2 cm as well as volume of EC are statistically significantly higher in subjects with MI $>$50%. A significant finding of our study is that the difference in the average distance of the EC from the serosa is 1.1 cm between the two examined groups and is statistically significant.

The average degree of MI measured by the PHD method in our study was 42.71%, the difference between the two groups was significant. There are studies with higher and lower average degrees of MI. The average rate of MI in our study is similar to the study by Prueksaritanond et al. [9], 48.4%. In the study by Oge et al. [10], the average degree of MI was 70%, higher than in our study, given that it was only about patients with stage IB EC, while in the study by Kim et al. [11], the average degree of MI was 18.4%, lower than in our study considering the larger number of patients with IA stage EC.

In our study, according to the gold standard, PHD diagnosis, the superficial degree of MI (50%) is more common, which correlates with the majority of reviewed studies and with the fact that EC is detected at an early stage in most cases [5, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22].

Tumor size is the strongest single TVS predictor of high-risk EC. The three dimensions of EC obtained by TVS (expressed in centimeters) are statistically significantly higher in subjects with MI $>$50%. The AP diameter of the EC in our study is 21.3 mm, while in the Tatar study [21], it is 34.7 mm. Epstein et al. [8] analyzed EC diameter according to histological grades G1 (13 mm), G2 (17 mm) and G3 (23.5 mm), and came to the conclusion that tumor size (diameter and volume) is very important for distinguishing low-risk and high-risk tumors EC. Frühauf et al. [5] measured all three tumor diameters (antero-posterior, cranio-caudal and latero-lateral) and obtained values similar to those in our study.

There is a significant difference in prognosis and treatment between patients with EC smaller than 2 cm or larger than 2 cm [23]. The diagnostic performance of AP tumor diameter $>$2 cm is similar to the Karlsson method in the prediction of deep MI. AP tumor diameter greater than 2 cm increases the chance of metastasis to the lymph nodes [24]. In our study, the frequency of AP EC diameter greater than 2 cm was significantly higher in the group of subjects with MI $>$50%. In the total AP sample, tumor diameter greater than 2 cm was present in 48.3% of cases, similar to the study by Eriksson et al. [25], 43.2%.

In the study by Epstein et al. [8], EC volume was shown in different histological grades G1 (5.1 mL), G2 (7.7 mL) and G3 (14.9 mL). The most significant TVS difference between high-grade and low-grade EC is the size of the tumor (diameter and volume), color score, shape of blood vessels, and damage to the endomyometrial zone [8]. In our study, the average EC volume for the entire sample was 10.6 mL. In the MI 50% group it was 6.1 mL, and in the MI $>$50% group 16.58 mL, significantly higher, with a difference of 10.48 milliliters compared to the group of subjects with MI 50%. We suggest cut off value for EC volume in differentiating deep myometrial invasion form superficial is 10.48 milliliters.

The volume of EC successfully reflects the stage of the disease, the prognosis and the type of surgery required. The percentage of patients with high-risk pathohistological findings (grade 3 and non-endometrioid EC type), deep MI, lymph node invasion, and extrauterine spread of the disease increases with increasing EC volume [23]. The volume of the EC is important for making a decision on the type of surgery required. Preoperatively measured EC volume by MRI can provide useful information about EC stage, lymph node invasion, prognosis, and required surgical treatment. However, the volume of EC is not superior than assessment of the degree of MI in predicting the presence of metastases in the lymph nodes [23].

The distance of EC from the serosa measured by TVS is a promising diagnostic and prognostic marker. Liro et al. [26] compared the usefulness of the distance of EC from the serosa and the degree of MI in assessing the locoregional extension of the disease and lymph node invasion. They came to the conclusion that both methods, alone or in combination, are a significant aid in obtaining preoperative information about the status of lymph nodes. They believe that the use of the distance of EC from the serosa is easier compared to measuring the degree of MI as a marker of EC invasion, given that both methods have similar predictive value in the assessment of invasion and lymph node status. The cut-off value of the distance from the serosa is 5.2 mm in the prediction of lymph node metastases [26].

The distance of the EC from the serosa—the minimal tumor-free zone measured by TVS, is greater in the group of subjects with MI 50%, and smaller in the subjects with MI $>$50%. The difference in the average distance of the EC from the serosa is 11 mm between the two examined groups, which is significant. The average distance from the serosa in our study was 11 mm, while in the study by Liro et al. [26] it was 7.39 mm. Thus, our study confirmed that the distance of EC from the serosa correlates with the degree of MI. We suggest cut off value for minimum free myometrial zone in differentiating deep myometrial invasion form superficial is 11 mm.

The kappa concordance coefficient for the subjective method of TVS versus PHD findings was significant, and was kappa = 0.72, significantly higher than in the study by Eriksson et al. [13], in which it was 0.52 and 0.48, while in the study by Savelli et al. [27] it was 0.67. The subjective method of TVS against the gold standard in the diagnosis of MI $>$50% has a good diagnostic value, better than in the studies analyzed below, sensitivity 77%, specificity 94%, positive predictive value (PPV) 91%, negative predictive value (NPV) 84% and overall accuracy 87%.

For the subjective TVS method, the reviewed studies reported sensitivity from 56% to 85%, specificity from 69% to 91.3%, PPV from 61% to 79%, NPV from 79% to 92% and overall accuracy from 75.7% to 84% [4, 5, 13, 14, 15, 16, 21, 24, 27, 28, 29].

In a large prospective study, the performance of subjective and objective TVS methods in the detection of deep MI in grade 1 and 2 EC was compared. A subjective prediction model, which included the histological grade of EC and a subjective assessment of the degree of MI, and an objective prediction model, which included the histological grade and an objective measurement of the distance of the EC from the serosa, were also used. In the three analyzed studies, they came to the conclusion that subjective TVS assessment is superior to ultrasound measurements, objective TVS methods in assessing the degree of MI [5, 14, 24].

Based on our experience during the conducted study, we can list several differences between endometrial hyperplasia, endometrial polyps and endometrial cancer which may be of practical importance. Endometrial hyperplasia gives an ultrasound image of inhomogeneous, hyperechoic and thickened endometrium with small cysts. In the case of an endometrial polyp, there is a clearly limited hyperechoic formation inside the uterine cavity, usually with a scant amount of fluid in the uterine cavity. Ultrasound characteristics of endometrial cancer are thickened endometrium, $>$6 mm, inhomogeneous and hyperechoic, in the case of myometrial invasion, a visible break in the continuity of the endomyometrial halo, the presence of fluid in the uterine cavity.

Our study has limitations, primarily a small sample of study participants and a short period of sample collection. The advantage of the study refers to the prospective, and to the fact that one person performed ultrasound examinations and analyzed all study participants.

The three dimensions, as well as the volume of endometrial cancer, obtained by TVS, are significantly higher in subjects with $>$50% myometrial invasion; there is also a significantly higher frequency of EC diameter greater than 2 cm in the group of subjects with $>$50% myometrial invasion.

The subjective method of TVS has a good diagnostic accuracy in the diagnosis of myometrial invasion $>$50% compared to the histopathology as gold standard.

All data points generated or analyzed during this study are included in this article and there are no further underlying data necessary to reproduce the results.

AC designed the research study. AC performed the research. DH and ZH provided help and advice on the experiments and analyzed the data. All authors contributed to editorial changes in the manuscript. All authors have read and approved the final manuscript.

All subjects gave informed consent to be included before participating in the study. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of the University Clinical Center Tuzla (approval number No 02-09/2-2/20).

Thanks to all the peer reviewers for their opinions and suggestions which improved the quality of our manuscript.

This research received no external funding.

The authors declare no conflict of interest. Dubravko Habek is serving as one of the Editorial Board members/Guest editors of this journal. We declare that Dubravko Habek had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Michael H. Dahan.