Endogenous estrogen metabolites as oxidative stress mediators and endometrial cancer biomarkers.

BACKGROUND: Endometrial cancer is the most common gynecologic malignancy found in developed countries. Because therapy can be curative at first, early detection and diagnosis are crucial for successful treatment. Early diagnosis allows patients to avoid radical therapies and offers conservative management options. There are currently no proven biomarkers that predict the risk of disease occurrence, enable early identification or support prognostic evaluation. Consequently, there is increasing interest in discovering sensitive and specific biomarkers for the detection of endometrial cancer using noninvasive approaches. CONTENT: Hormonal imbalance caused by unopposed estrogen affects the expression of genes involved in cell proliferation and apoptosis, which can lead to uncontrolled cell growth and carcinogenesis. In addition, due to their ability to cause oxidative stress, estradiol metabolites have both carcinogenic and anticarcinogenic properties. Catechol estrogens are converted to reactive quinones, resulting in oxidative DNA damage that can initiate the carcinogenic process. The molecular anticancer mechanisms are still not fully understood, but it has been established that some estradiol metabolites generate reactive oxygen species and reactive nitrogen species, resulting in nitro-oxidative stress that causes cancer cell cycle arrest or cell death. Therefore, identifying biomarkers that reflect this hormonal imbalance and the presence of endometrial cancer in minimally invasive or noninvasive samples such as blood or urine could significantly improve early detection and treatment outcomes.

Perioperative and Long-Term Anatomical and Subjective Outcomes of Laparoscopic Pectopexy and Sacrospinous Ligament Suspension for POP-Q Stages II-IV Apical Prolapse.

The aim of this paper was to analyze perioperative and long-term outcomes in 114 women undergoing surgery for POP-Q ≥ 2 apical prolapse: sacrospinous ligament colpo/hysteropexy (SSLF/SSHP)­61; laparoscopic pectopexy (LP)­53. Validated questionnaires (PGI-I, ISI, #35 EPIQ, PFIQ-7, PFDI-20) were completed at baseline and follow-up. POP-Q stages II, III and IV were diagnosed in 1 (0.9%), 84 (73.7%) and 29 (25.4%) patients, respectively. Mean operative time and hospital stay were 151.8 ± 36.2 min/2.6 ± 1.1 days for LP and 69 ± 20.4 min (p < 0.001)/2.7 ± 1.0 days for SSLF. Severe intraoperative complications occurred in two (1.8%) patients. Mean follow-up was 26.9 ± 12 and 37.3 ± 17.5 months for LP and SSLF, respectively. At follow-up, significant improvement for all POP-Q points was observed in both groups (p < 0.001). Shortening of total vaginal length was found in both groups, but predominantly in SSLF patients (p = 0.01). The sensation of vaginal bulge (EPIQ) was reduced, and total PFDI-20 and PFIQ-7 scores improved (p < 0.04) in both groups. Subjective success was reported by 40 (75.5%) LP and 44 (72.1%) SSLF patients. ISI detected no deterioration in urinary incontinence. PGI-I, PFDI-20, #35 EPIQ, PFIQ-7 and ISI did not differ between the groups. In conclusion both, SSLF and LP for apical prolapse generate good anatomical and subjective outcomes, with protective effect on the anterior compartment observed for LP.

Comprehensive Review of Fluorescence Applications in Gynecology.

Since the introduction of indocyanine green (ICG) as a fluorophore in near-infrared imaging, fluorescence visualization has become an essential tool in many fields of surgery. In the field of gynecology, recent new applications have been proposed and found their place in clinical practice. Different applications in gynecology were investigated, subcategorized, and overviewed concerning surgical applications and available dyes. Specific applications in which fluorescence-guided surgery was implemented in gynecology are described in this manuscript-namely, sentinel node biopsy, mesometrium visualization, angiography of different organs, safety issues in pregnant women, ureters visualization, detection of peritoneal metastases, targeted fluorophores for cancer detection, fluorescent contamination hysterectomy, lymphography for lower limb lymphedema prevention, tumor margin detection, endometriosis, and metastases mapping. With evolving technology, further innovative research on the new applications of fluorescence visualization in cancer surgery may help to establish these techniques as standards of high-quality surgery in gynecology. However, more investigations are necessary in order to assess if these innovative tools can also be effective to improve patient outcomes and quality of life in different gynecologic malignancies.

Laparoscopic Pectopexy-CUSUM Learning Curve and Perioperative Complications Analysis.

The study aimed to examine the learning curve and perioperative complications for laparoscopic pectopexy (LP). A total of 60 women with stage II-IV apical prolapse who underwent LP were dichotomized into groups: LSH(+) with concomitant laparoscopic supracervical hysterectomy (LSH), LSH(-) after previous supracervical/total hysterectomy. Operative time, estimated blood loss and hospitalization length were evaluated with cumulative sum (CUSUM) analysis and the Kwiatkowski-Phillips-Schmidt-Shin (KPSS) test, separately for two surgeons (A and B). Intraoperative and perioperative complications according to the Clavien-Dindo (C-D) classification were analyzed. Mean operative time, change in hemoglobin level, and postoperative hospital stay were 143.5 ± 23.1 min-1.5 ± 0.5g/dL and 2.5 ± 0.9 days, respectively. LSH during pectopexy was associated with longer operative time (p = 0.01) but not with higher intraoperative bleeding or prolonged hospital stay. Severe complications rate was low (1.7%) with one bowel injury in LSH(-) (C-D grade IIIb). No C-D grade II, IV and V complications were found. Conversion to open pectopexy, return to the operating room or blood transfusion were not required. The KPSS test showed that a steady operative time for Surgeon A was achieved after 28 procedures. A proficiency for laparoscopic pectopexy based on CUSUM analysis was observed after 38-40 procedures.

Interactions of ficolin-3 with ovarian cancer cells.

BACKGROUND: Ficolin-3 is a pattern-recognition molecule with the ability to activate the lectin pathway of complement. It is found in lung, liver and blood, but its physiological role is unclear. We have investigated interaction of recombinant ficolin-3 with malignant cells and tissues. MATERIAL AND METHODS: Cells of various lines of human origin as well as ovarian tissue sections have been studied with the use of flow cytometry and immunohistochemistry. RESULTS: Recombinant (but not serum-derived) ficolin-3 was found to bind strongly to the ovarian cancer cell lines, SKOV-3, OVCAR-3 and ES-2, at concentrations of 2.5 µg/ml and above. Moreover, His-tagged recombinant ficolin-3 (10 µg/ml) preferentially stained ovarian tissue sections from patients with malignant tumours compared with those from patients without. Binding to cell lines was inhibited by EDTA and specific carbohydrate ligands, indicating involvement of the fibrinogen-like domain. Binding was enhanced under mildly acidic conditions and at physiological pH after pre-incubation of cells with mildly acidic buffer. CONCLUSION: Basing on data concerning recombinant protein, it may be suggested that ficolin-3 is involved in immune response in ovarian cancer. However, unidentified serum factor(s) seem(s) to protect cancer cells from recognition by natural or rficolin-3.

The impact of low volume lymph node metastases and stage migration after pathologic ultrastaging of non-sentinel lymph nodes in early-stage cervical cancer: a study of 54 patients with 4.2 years of follow up.

OBJECTIVES: To assess the significance of pathologic ultrastaging (PU) of sentinel (SLN) and non-sentinel (nSLN) lymph nodes (LNs) and the influence on cancer staging in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA2-IB1 cervical cancer. MATERIAL AND METHODS: A retrospective study was conducted with 54 patients divided into two equal-sized groups. In test group (n1), at least one SLN/patient was detected with blue dye. All excised LNs in this group were subjected to PU (4 µm slices/150 µm intervals) with hematoxylin-eosin staining and immunohistochemistry (AE1-AE3 antibodies). In none of the control group (n2) was PU performed, but in 2 patients SLN concept was performed. Patients in both groups underwent radical hysterectomy and lymphadenectomy. The effect of PU was expressed in puTNM and compared with both standard pTNM and FIGO systems. The influence of PU on patients' disease-free survival (DFS) and overall survival (OS) was assessed using Kaplan-Meier curves. RESULTS: In total, 516 LNs were extracted (66 SLNs, 36% bilaterally). Micrometastases (MIC) or isolated tumor cells (ITC) were detected in 34 of the 482 LNs (7.1%), including 16 MICs and 9 ITC in non-SLNs. False negative rates were: 3.7%/side-specific, and 7.4%/both sides. The use of PU resulted in stage change in 2 cases (N and M status change), FIGO stage did not changed. No PU impact on DFS or OS was observed. CONCLUSIONS: The risk of TNM stage migration in early cervical cancer is low, is more likely in inattentively evaluated patients, and has indeterminate prognostic and predictive value. Selection of cases with cT ≤ 2 cm and cN0 is sufficient to avoid the risk of improper staging.

Conservative treatment of borderline ovarian tumors: the experience of one clinical center.

OBJECTIVES: Borderline ovarian tumors have favorable survival rates, however, prognostic factors are still discussed. The aim was to investigate the outcome for women treated conservatively with respect to different tumor-dependent and tumor-independent prognostic factors. MATERIAL AND METHODS: 194 women treated surgically between years 1978 and 2007. Influence of conservative or radical surgical treatment on survival was evaluated. RESULTS: The overall 5-year survival rate was 93.1% and 96.8% respectively for radical and conservative treatment. The mean time of survival was longer in women treated conservatively (p = 0.03), but this was an outcome of their younger age; when age was eliminated as a determining factor; the type of treatment had not influenced the length of postoperative survival (p=0.57). Conservative treatment was chosen more frequently for younger women. Factors that are detrimental to survival are age, postmenopausal detection of borderline ovarian tumors, an advanced stage of progression, a bilateral localization of tumors, the occurrence of invasive peritoneal implants and a serous rather than a mucinous histological type of borderline ovarian tumor more frequently occurred in women treated radically Borderline ovarian tumors recurred in 16.7% of women after conservative treatment and in 3.5% of women after radical treatment. Of women with preserved fertility 25.7% became pregnant at least once and 21.2% of the group as a whole delivered children at term; none of the pregnancies were fertility-assisted. CONCLUSIONS: Conservative treatment does not have a deleterious effect on the prognosis of women provided that unfavorable prognostic factors are identified.

[Micrometastases in sentinel lymph node in endometrial cancer patients]. / Mikroprzerzuty w wartowniczym wezle chlonnym u chorych na raka endometrium.

BACKGROUND: Detection of micrometastases in sentinel lymph nodes (SLN) extends our knowledge of lymphatic spread in endometrial cancer, although its clinical significance has not yet been confirmed. OBJECTIVES: The aim of study was to determine the incidence of SLN micrometastases and to analyze the association between micrometastases and disease relapse. MATERIAL AND METHODS: Fifty-four patients with endometrioid endometrial cancer underwent routine surgical therapy and sentinel lymph node biopsy (SLNB). SLNB was performed using two techniques: cervical injection of 99mTc-labelled albumin or blue dye and fundal injection of blue dye. SLNs were subjected to ultrastaging with immunohistochemistry (AE1/AE3, 150µm). RESULTS: At least one SLN was detected in 51 patients (94.4%) and bilateral SLN detection was achieved in 80.4%. Nodal macrometastases were found in 3 patients (6.3%). SLNB enabled us to detect nodal macrometastases in 2 out of those 3 patients. In the third case, detection of SLN micrometastasis allowed to correctly determine the nodal status, thus avoiding the false negative result of SLNB. In 48 patients with detected 184 SLNs, there were 4 patients (8.3%) with micrometastases and 4 (8.3%) with ITC foci. No significant associations between the presence of risk factors (grade, myometrial invasion, cervical invasion, lymphovascular space invasion) and incidence of micrometastases and/or ITC foci in SLNs were found. CONCLUSIONS: Detection of micrometastases may result in lower false-negative rate, thus increasing SLNB safety.

Sentinel Lymph Node Biopsy in Endometrial Cancer--Comparison of 2 Detection Methods.

OBJECTIVES: Sentinel lymph node biopsy (SLNB) can identify patients with nodal metastases who are eligible for tailored treatment. The aim of study was to compare the SLN detection rates using cervical and subserosal administration of 2 tracers. RESULTS: In group 1 (82 patients), SLNB was performed using radiocolloid injected to the cervix and blue dye administered to the fundus. In group 2, blue dye was injected to cervix and fundus (106 patients). Only SLNB was performed in 128 (68.1%) women. In the remaining 60 (31.9%) patients, pelvic/para-aortic lymphadenectomy together with SLNB was performed. Groups 1 and 2 did not differ with regard to the frequencies of SLNB and lymphadenectomy. The detection rate for both groups was 90.9%. Bilateral detection was achieved in 72.5%. Para-aortic SLNs were found in 9.6%. Detection rates in groups 1 and 2 were 95.1% and 87.7% (P = 0.065). In comparison of cervical administration of radioisotope and subserosal injection of blue dye in group 1, we found a significant difference for total SLN detection (91.5% vs 74.4%, P < 0.05) and no significant difference for bilateral detection (73.3% vs 59.1%, P = 0.776). We did not find differences in the para-aortic SLN detection rates achieved after administration of a radiotracer and injection of a blue dye (4.9% vs 9.8%, P = 0.184). Eighteen patients (9.6%) presented with nodal disease, including 15 women with SLN involvement. The false-negative rate, calculated for patients subjected to lymphadenectomy, was 12.5% (1/8); using the SLNB surgical algorithm, it was 10% (1/10). CONCLUSIONS: Cervical administration of a tracer, especially radioisotope, results in high SLN detection rates. In turn, the subserosal injection can be used only as an adjuvant method for SLNB. Low para-aortic SLN detection rates observed after cervical administration of a tracer do not seem to be a serious limitation of this technique.

[Endometrial cancer in young women--clinical and molecular aspects]. / Rak blony sluzowej trzonu macicy u mlodych kobiet--aspekty kliniczne i molekularne.

OBJECTIVES: The aim the study was to compare two groups of endometrial cancer patients (below and above 45 years of age) in the aspect of clinicopathological and molecular data. MATERIAL AND METHODS: The study encompassed 456 primary tumour samples retrospectively collected from a cohort of endometrial cancer patients, primarily treated by surgery Molecular analysis covered: copy number variations of 10 genes (TOP2A, ERBB1, ERBB2, ERBB3, ERBB4, MYC, CCND1, ESR1, PIK3CA, RAD21) analyzed by quantitative PCR; mRNA expression of 6 genes (SCGB2A2, RAD27, RUNX1, SNAI1, SNAI2, PROM1) analyzed with the use of reverse transcription quantitative PCR; protein expression analysis of 8 markers (PGR, ESR1; ERBB1, ERBB2, ERBB3, ERBB4, TOP2A, pAKT1) performed with the use of immunohistochemistry. RESULTS: The younger group of patients was characterized by less frequent hypertension (p <0.00007), less frequent myometrial infiltration (p=0.002) and longer overall survival (p=0.003). Apart from RAD21 gene aberrations, which were more frequent in younger patients (p=0.02), the study revealed no statistically significant differences between the groups. CONCLUSIONS: The study showed no molecular differences in the profile of younger and older endometrial cancer patients. Data on both the prognostic and predictive significance of RAD21 in endometrial cancer are still insufficient. The clinical profile of younger patients with endometrial carcinoma was slightly better when compared to elderly patients. Younger patients were characterized by longer overall survival.

Mannose-Binding Lectin (MBL) and MBL-associated serine protease-2 (MASP-2) in women with malignant and benign ovarian tumours.

Mannose-Binding Lectin (MBL) is a serum pattern recognition molecule, able to activate complement in association with MASP proteases. Serum levels of MBL and MASP-2, activities of MBL-MASP complexes, single nucleotide polymorphisms of the MBL2 and MASP2 genes and/or their specific mRNA expression in ovarian sections were investigated in 128 patients suffering from primary ovarian cancer (OC) and compared with 197 controls (C), encompassing both patients with benign ovarian tumours (n = 123) and others with no ovarian pathology (n = 74). MBL deficiency-associated genotypes were more common among OC patients than among controls. The O/O group of genotypes was associated with ovarian cancer (OR 3.5, p = 0.02). In A/A homozygotes, MBL concentrations and activities were elevated in the OC group and correlated with C-reactive protein. Moreover, high MBL serum levels were associated with more advanced disease stage. No differences in distribution of the MASP2 +359 A>G (D120G) SNP or MASP-2 serum levels were found between cancer patients and their controls. However, the highest frequency of the A/G (MASP2) and LXA/O or O/O (MBL2) genotypes was found among OC patients with tumours of G1-2 grade (well/moderately differentiated). Furthermore, MBL deficiency-associated genotypes predicted prolonged survival. None of the parameters investigated correlated with CA125 antigen or patients' age. The local expression of MBL2 and MASP2 genes was higher in women with ovarian cancer compared with controls. It is concluded that the expression of MBL and MASP-2 is altered in ovarian cancer, possibly indicating involvement of the lectin pathway of complement activation in the disease.

Clinical feasibility and diagnostic accuracy of detecting micrometastatic lymph node disease in sentinel and non-sentinel lyph nodes in cervical cancer: outcomes and implications.

BACKGROUND: Lymph node (LN) micrometastatic disease has come to prominence since ultrastaging was shown to improve the quality of LN procedures in epithelial cancers. The aim of the study was to evaluate the feasibility and diagnostic usefulness of detecting micrometastases in sentinel (SLN) and non-sentinel LNs (nSLN) in cervical cancer MATERIAL AND METHODS: Twelve consecutive patients with cervical cancer stages IA to IIA, classified according to the Union for International Cancer Control (UICC) and divided into two groups: A (7) and B (5), with and without SLN procedure with methylene blue dye, who underwent radical hysterectomy and lymph nodes removal, were recruited for the study. All LNs were evaluated in hematoxylin-eosin (HE) staining and immunohistochemically (IHC) in ultrastaging with anti-cytokeratin AE1/AE3 antibodies. A detailed analysis was performed with regard to the technical and histopathological aspects of the procedure. RESULTS: More LNs could be extracted and studied in group A as compared to group B (210 vs. 70, mean 30 vs. 14, respectively p < 0.0005). A total of 13 SLNs were extracted, and the identification rate was 71% (5/7 in group A). One micrometastatic LN was found in each of the groups (16% cases), but the preliminary classification of the advancement stage was changed only in 1 case from the labeled nodes group (group A--from pN0 with HE to pN1 with IHC). CONCLUSIONS: Presence or absence of metastases in SLN(s) should not be sufficient amount of information for a surgeon or an oncologist, who ought to have data about all of the removed lymph nodes (sent to ultrastaging). In order for the surgery to be performed properly it is vital to ensure that SLNs were removed. Assessment of the N status ought to be taken into consideration in the classification according to the International Federation of Gynecology and Obstetrics (FIGO).

The importance and perspective of magnetic resonance imaging in the evaluation of endometriosis.

MR imaging is becoming increasingly important in the assessment of patients with endometriosis. Its multiplanar capabilities and superior soft tissue contrast are particularly useful in the detection of deep infiltrating endometriotic implants. Endometriosis, defined as the presence of endometrial glands and stroma outside the endometrium, is among the most common gynaecological disorders affecting women in their reproductive age. The diagnosis and evaluation of the extension of endometriosis are difficult only with physical examination and laparoscopy. According to the authors' personal experience, a special MRI technique and some imaging guidelines regarding different anatomical localizations of endometriosis are discussed. This review is a brief presentation of current evidence on the diagnostic accuracy of MRI in the evaluation of endometriosis concerning other diagnostic methods, the limitations of MRI and its essential usefulness for preoperative diagnosis of deep pelvic endometriosis, and future perspectives in monitoring this disease.

[Clinical significance of lymph node micrometastases in cervical cancer]. / Kliniczne znaczenie mikroprzerzutów w wezlach chlonnych w raku szyjki macicy.

In most cancers of epithelial origin, metastases to the lymph nodes constitute the most important prognostic factor and are predictive of the results of the surgical and adjuvant therapies. Data on the lymph node status allows to design an appropriate treatment plan. Despite advances in gynecologic oncology the importance of lymph node micrometastases in cervical cancer especially in nonsentinel lymph nodes which are detected by ultrastaging, has not been fully elucidated. The purpose of the article is to familiarize the reader with the state of current knowledge on cervical cancer micrometastases. The authors attempt to answer the question about the benefits of lymph node assessment in the search for micrometastases in cervical cancer as well as to address emerging doubts.

Preoperative detection of sentinel lymph nodes in endometrial cancer using SPECT/CT.

We report the use of SPECT/CT in sentinel lymph node biopsy in endometrial cancer. The patient was a 54-year-old woman with the diagnosis of endometrial adnenocarcinoma, grade 2. Preoperative MRI and transvaginal ultrasound scans revealed tumor infiltrating more than 50% of the myometrium. The patient was qualified for total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic/paraaortic lymphadenectomy. Before the surgery, 2 cervical injections of the (99m)Tc-labeled nanocolloid (0.5 mCi) were administered and the SPECT/CT was performed using a standard dual-head gamma camera and a 6-slice spiral CT component.

Ficolin-2 and ficolin-3 in women with malignant and benign ovarian tumours.

Ficolins are serum pattern recognition molecules. They have opsonic properties and are able to activate complement via the lectin pathway. This paper reports investigations concerning ficolin-2 and ficolin-3 in ovarian cancer (OC). Their serum levels, single nucleotide polymorphisms of the corresponding FCN2 and FCN3 genes and specific mRNA expression in ovarian sections were investigated in 128 patients suffering from primary OC and 197 controls operated on for reasons other than malignancies. The latter consisted of two reference groups: those with benign tumours (n = 123) and those with normal ovaries (NO) (n = 74). Serum ficolin-2 and ficolin-3 concentrations were higher among patients with malignant disease when compared with either of the reference groups. A significant correlation between ficolin-2 and ficolin-3 concentrations was found, while no correlations with CA125 antigen or CRP were observed. No differences in the frequency of single nucleotide polymorphisms at sites -64, -4 (promoter), +6359, or +6424 (exon 8) (FCN2 gene) nor in the frame-shift mutation 1637delC (FCN3 gene) were found between investigated groups. In contrast to serum concentrations, the expression of FCN2 gene (reported for the first time in ovarian sections) was significantly lower in women with OC in comparison with patients with NO but not with benign ovarian tumours. In case of FCN3 gene, its expression levels in OC group inversely correlated with serum ficolin-3 and were lower in comparison with controls.

Comparison of SPECT-CT results and intraoperative detection of sentinel lymph nodes in endometrial cancer.

OBJECTIVES: The aim of the study was to compare the results of single-photon emission computed tomography-computed tomography (SPECT-CT) with those of intraoperative gamma probe detection and assess the clinical utility of SPECT-CT for sentinel lymph node biopsy in endometrial cancer. MATERIALS AND METHODS: We investigated 70 patients with endometrial cancer who underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and sentinel lymph node biopsy (routine pelvic and para-aortic lymphadenectomy was additionally performed in high-risk patients). Tc-99m radiocolloid albumin was injected into the cervix and a blue dye was injected superficially into the fundus. RESULTS: SPECT-CT revealed hot spots in 64 patients (91.4%). The detection rates were 97.1 and 94.3% using the combined technique and the hand-held gamma probe, respectively. In 19 cases (27.1%) 35 hot spots detected on SPECT-CT were not diagnosed as sentinel lymph nodes (SLNs) during surgery. In each patient with undetected hot spots located in the common iliac or para-aortic regions, hot SLNs were found during surgery in the obturator or external iliac region. In addition, SPECT-CT had detected 88.9% of the SLNs found during surgery. With respect to the 13 cases not detected on SPECT-CT, the hot SLNs had very low activity. Using the combined method, 95.1% of SLNs were found in typical locations (external iliac or obturator nodes). There were two metastatic nodes: one in SLN and one in nonsentinel node. CONCLUSION: SPECT-CT yields a high SLN detection rate; however, there is significant discrepancy in comparison with intraoperative findings, which limits its clinical utility. In addition, in the majority of cases SLNs are found in typical areas, which means that they can be reliably detected using an intraoperative gamma probe.

Deregulation of RAD21 and RUNX1 expression in endometrial cancer.

Cohesins and cohesin-regulated genes are deregulated in numerous types of human cancer. However, data concerning their status and role in endometrial cancer are scarce. This study aimed to determine the clinical significance of double-strand-break repair protein rad21 homolog (RAD21) and runt-related transcription factor 1 (RUNX1) gene dosage and mRNA expression in endometrial cancer. RAD21 is a component of the cohesin complex, crucial for chromosome segregation and DNA repair. RUNX1 is the transcription factor implicated in RAD21 regulation. The study group included 144 endometrial cancer patients. RAD21 and RUNX1 expression profiles were measured by reverse-transcription quantitative PCR. RAD21 gene dosage was determined by quantitative PCR. RAD21 gene dosage was associated with RAD21 mRNA expression (ϱ=0.22; p=0.009). Furthermore, RAD21 expression strongly correlated with RUNX1 expression (ϱ=0.43; p<0.0000001). Increased RAD21 gene dosage correlated with more advanced tumor stage (p=0.021), higher grade (p=0.021), cervical involvement (p=0.01) and the absence of obesity (p=0.025), while RAD21 mRNA expression correlatd with cervical involvement (p=0.027). The mRNA expression of RAD21 and RUNX1 was found to be deregulated and co-dependent in endometrial cancer. RAD21 gene dosage is associated with unfavorable tumor characteristics. However, elucidating the role of these molecular markers in endometrial oncogenesis requires further investigation, including functional studies and survival analysis.