Utility of expression of 4-hydroxynonenal tested by immunohistochemistry for cervical cancer.

Introduction: Cervical cancer (CC) is a leading cause of mortality in women around the world, with the highest incidence rate still being in developing countries. The most common aetiological factor is infection with high-risk human papilloma virus viral strains. Oxidative stress through generation of reactive oxygen species leads to lipid peroxidation and DNA damage. Studies show that reactive lipid electrophiles such as 4-hydroxynonenal (4-HNE) produced in the process play an important role in cancer signalling pathways and are a good biomarker for oxidative stress. We aim to investigate the prognostic role of 4-HNE as a biomarker for oxidative stress in patients in early and advanced stages of CC measured by immunohistochemistry. Material and methods: This is a retrospective study of 69 patients treated at our Department of Oncogynaecology. Paraffin embedded tumour tissues were immunohistochemically tested for the levels of expression of 4-HNE. The results for H-score, Allred score, and combined score were investigated for association with tumour size, lymph node status, andInternational Federation of Gynaecology and Obstetrics stage. Results: 4-hydroxynonenal showed higher expression in more advanced stages of CC and in cases with involved lymph nodes. Tumour size was not associated with the levels of 4-HNE. Conclusions: To best of our knowledge, this is the first study to use immunohistochemistry to examine the expression of 4-HNE as a prognostic factor in CC. The 3 score systems showed similar results. The pattern of 4-HNE histological appearance is dependent on the histological origin of cancer and is not universal.

Tackling hurdles in front of young clinical investigators in oncology - Results from an international survey.

INTRODUCTION: Cancer is a leading cause of morbidity and mortality worldwide, and coordinated research efforts are vital to improve global outcomes. Clinical or translational research is usually planned, coordinated and executed by clinical researchers. With this survey we aimed to identify the main hurdles in front of young clinical investigators in oncology. METHODS AND MATERIALS: An anonymized survey was distributed using social media between April and November 2022. Target population were health-care professionals in the field of oncology - physicians, nurses and researchers. We divided participants according to working experience (<40 vs. >40 years of age) and country of practice (Europeans vs. non-Europeans). RESULTS: We received 121 responses from participants practicing in 36 countries. Eighty-seven (72%) of the participants were under 40 years. Eighty-nine (74%) were from European countries and thirty-two (26%) were from non-European. Experienced and European professionals were more likely to be involved in all different aspects of clinical trials. The main source of funding - independently of geographic location - were industry grants. Investigators out of Europe have less participation in international grants. Over 50% of participants dedicate time for clinical research from their personal time and are not paid for it. Almost 50% of investigators don't have access to an experienced mentor in their institution. CONCLUSION: The majority of respondents to our survey are active clinical researchers. Our data indicate that access to education and training as well as possibilities for appropriate networking, and specifically lack of mentorship, are key limiting factors in developing clinical research by healthcare professionals.

The Role of FBXW7 in Gynecologic Malignancies.

The F-Box and WD Repeat Domain Containing 7 (FBXW7) protein has been shown to regulate cellular growth and act as a tumor suppressor. This protein, also known as FBW7, hCDC4, SEL10 or hAGO, is encoded by the gene FBXW7. It is a crucial component of the Skp1-Cullin1-F-box (SCF) complex, which is a ubiquitin ligase. This complex aids in the degradation of many oncoproteins, such as cyclin E, c-JUN, c-MYC, NOTCH, and MCL1, via the ubiquitin-proteasome system (UPS). The FBXW7 gene is commonly mutated or deleted in numerous types of cancer, including gynecologic cancers (GCs). Such FBXW7 mutations are linked to a poor prognosis due to increased treatment resistance. Hence, detection of the FBXW7 mutation may possibly be an appropriate diagnostic and prognostic biomarker that plays a central role in determining suitable individualized management. Recent studies also suggest that, under specific circumstances, FBXW7 may act as an oncogene. There is mounting evidence indicating that the aberrant expression of FBXW7 is involved in the development of GCs. The aim of this review is to give an update on the role of FBXW7 as a potential biomarker and also as a therapeutic target for novel treatments, particularly in the management of GCs.

Current practice in assessment and management of malnutrition in surgical oncology practice - An ESSO-EYSAC snapshot analysis.

INTRODUCTION: Malnutrition is common in patients suffering from malignant diseases and has a major impact on patient outcomes. Prevention and early detection are crucial for effective treatment. This study aimed to investigate current international practice in the assessment and management of malnutrition in surgical oncology departments. MATERIAL AND METHODS: The survey was designed by European Society of Surgical Oncology (ESSO) and ESSO Young Surgeons and Alumni Club (EYSAC) Research Academy as an online questionnaire with 41 questions addressing three main areas: participant demographics, malnutrition assessment, and perioperative nutritional standards. The survey was distributed from October to November 2021 via emails, social media and the ESSO website to surgical networks focussing on surgical oncologists. Results were collected and analysed by an independent team. RESULTS: A total of 156 participants from 39 different countries answered the survey, reflecting a response rate of 1.4%. Surgeons reported treating a mean of 22.4 patients per month. 38% of all patients treated in surgical oncology departments were routinely screened for malnutrition. 52% of patients were perceived as being at risk for malnutrition. The most used screening tool was the "Malnutrition Universal Screening Tool" (MUST). 68% of participants agreed that the surgeon is responsible for assessing preoperative nutritional status. 49% of patients were routinely seen by dieticians. In cases of severe malnutrition, 56% considered postponing the operation. CONCLUSIONS: The reported rate of malnutrition screening by surgical oncologists is lower than expected (38%). This indicates a need for improved awareness of malnutrition in surgical oncology, and nutritional screening.

Endometrial carcinoma in patients under 40 years of age: insights from the Bulgarian Cancer Registry.

OBJECTIVES: We aimed to investigate the overall survival (OS) of young women with endometrial cancer (EC) in Bulgaria and the impact of histological type on survival. MATERIAL AND METHODS: This is a population-wide retrospective study of patients with EC (≤ 40 years at diagnosis) registered at Bulgarian National Cancer Registry (BNCR) between 1993 and 2020. Patients were re-classified according to the 8th edition of the TNM classification. RESULTS: In total, 30 597 patients were registered and histologically confirmed with malignant tumors of the uterine body. From that, 29 065 of them (95%) had ECs, and the rest had sarcomas. Around 1.64% of all malignant tumors of the uterine body are diagnosed in women under the age of 40. Most of them are diagnosed in the early stage. There was no significant difference in median OS for patients diagnosed before or after 2003. In recent years there was a slight improvement in survival and patients from the last cohort of this study had a 5-year survival rate of 92.5%. Patients with favorable pathology (T1, G1/2) had no lymph node involvement at the time of diagnosis and their 10-year survival rate was 94%. CONCLUSIONS: EC in young women is a rare disease. In most cases, patients are diagnosed in early stageT1, G1/2, N0 and their prognosis is excellent. However, the lack of improvement of OS of young patients with EC in the last three decades shows the need for treatment optimization.

The effects of ROMO1 on cervical cancer progression.

INTRODUCTION: More than 95% of the cases of Cervical cancer (CC) are now linked to infection with Human papilloma virus (HPV) but the infection alone is not sufficient for starting the oncogenesis. Reactive Oxygen Species (ROS) can promote CC cancerogenesis. ROMO1 is a protein that regulates the production of intracellular ROS and influences cancer cell invasion and proliferation. We aimed to investigate the impact of ROS in CC progression, measured by the expression of ROMO1. METHODS AND MATERIALS: This is a retrospective study of 75 patients treated at the Department of Oncogynecology, Medical University of Pleven, Bulgaria. Paraffin embedded tumor tissues were immunohistochemically tested for the levels of expression of ROMO1. The results for both Allred score and H-score were investigated for association with tumor size, lymph node status and FIGO stage. RESULTS: Levels of ROMO1 were significantly higher in FIGO1 stage compared to FIGO2 and FIGO3 according to both scores (for H-score FIGO1 vs FIGO2 p = 0.00012; FIGO 1 vs FIGO3 p = 0.0008; for Allred score FIGO1 vs FIGO2, p = 0.0029; FIGO1 vs FIGO3 (p = 0.012). Statistically significant difference was found according to the H-score between patients with and without metastatic lymph nodes (p = 0.033). CONCLUSION: To the best of our knowledge this is the first study testing immunohistochemically the expression of ROMO1 for CC progression. The levels of ROMO1 were significantly higher in early stage tumors compared to advanced. Bearing in mind that only 75 patients were tested, further studies are required to evaluate the value of ROS in CC.

Electronic brachytherapy for gynecological cancers - a systematic review.

Background: The purpose of this manuscript is to provide an in-depth literature review of the management of endometrial and cervical cancers with electronic brachytherapy. Materials and methods: An extensive literature search was performed and 9 articles were selected based on preset criteria. Results: The reviewed studies provided dosimetric and clinical results. Patient populations were diverse and prescribed doses varied. When treatment plans were compared to those using cobalt 60 (60Co) and iridium 192 (192Ir) sources researchers found lower or equivalent doses in organs at risk while the doses at the applicator surface were significantly higher for electronic brachytherapy. In the eligible studies, a total of 72 patients received treatment with AxxentXoft vaginal applicator, 29 were treated with the Intrabeam vaginal applicator, and 8 with AxxentXoft cervical applicator. Conclusions: All authors found that electronic brachytherapy was safe and well tolerated as higher mucosal doses did not present as adverse clinical effects. Electronic brachytherapy for gynecological cancers has the potential to achieve equivalent tumor control while minimizing bowel and urinary toxicity thus improving the quality of life. More clinical data is needed to stratify patients who would benefit the most.

Infiltration by Intratumor and Stromal CD8 and CD68 in Cervical Cancer.

Background and Objectives: The tumor microenvironment (TME) plays a major role in neoplastic development. Various types of cells can be found in the TME. These cells can be classified into two groups, immunosuppressive and immunostimulatory types, depending on the function they perform in the antitumor immune response (IR). By interacting both with each other and with tumor cells, different immune mechanisms are activated or inhibited, which can suppress or promote the development and progression of cervical cancer (CC). Our aim was to investigate some of the main components of the cellular immune response in TME-tumor-infiltrating cytotoxic T cells (Tc, CD8+) and tumor-associated macrophages (TAMs, CD68+)-in patients with CC. Materials and Methods: We analyzed 72 paraffin-embedded tumor tissues of patients diagnosed and treated at Medical University Pleven, Bulgaria. Patients were classified according to the 2018 FIGO (International Federation of Gynaecology and Obstetrics) classification. From each patient, we selected one histological slide with hematoxylin eosin staining. In a microscopic evaluation, CD8+ T lymphocytes and CD68+-positive macrophages were counted in the tumor and stroma of five randomly selected fields at ×40 magnification (HPF). We analyzed the relationship between intratumoral and stromal CD8 and CD68 expression and FIGO stage and N status. Results: There was no significant association between the expression levels of intratumoral and stromal CD68+ cells in the different FIGO stages and according to the lymph nodes' involvement. For CD8+ cells, the association of stromal infiltration was also not found, but T intratumor infiltration was associated with a higher FIGO stage, despite the fact that the results did not reach significance (p = 0.063, Fisher test). Intratumoral CD8+ cells were significantly associated with positive N status, (p = 0.035). Discussion: The separation of tumor-infiltrating cytotoxic T cells and tumor-associated macrophages into intratumoral and stromal is inconsequential. In our study, the level of infiltration of CD68+ cells in tumors and stromata was not significantly associated with tumor progression or lymph node involvement. The results were different for CD8+ cells, in which levels of infiltration were associated with lymph nodes' statuses. Conclusions: The separate evaluation of CD68+ immune cells in the TME as intratumoral and stromal is not beneficial for defining prognoses, since the presence of these cells is not associated with the patient's stage. In our study, the presence of CD8+ cells was significantly associated with lymph node metastases. The prognostic value of the obtained results can be enriched with an additional study of the lymphocyte phenotype, including B and other subtypes of T lymphocytes, NK cells, as well as molecules involved in the immune response, such as HLA subtypes.

Cancer of the Cervix in Bulgaria: Epidemiology of a Crisis.

Eastern Europe continues to have the highest rates of cancer of the uterine cervix (CUC) and human papillomavirus (HPV) infection in Europe. AIM: The aim of this study was to investigate CUC trends in Bulgaria in the context of a lack of a population-based screening program and a demographic crisis. METHODOLOGY: This was a retrospective study of 7861 CUC patients who were registered in the Bulgarian National Cancer Registry (BNCR) between 2013 and 2020 and followed up with until March 2022. We used descriptive statistics and modeling to assess temporal trends in new CUC incidence rates and identify factors associated with survival. RESULTS: Bulgaria's population has decreased by 11.5% between 2011 and 2021. The CUC incidence rate decreased from 29.5/100,000 in 2013 to 23.2/100,000 in 2020 but remains very high. The proportion of patients diagnosed in earlier stages of CUC has decreased over time. Up to 19% of patients with CUC in Bulgaria are diagnosed between the age of 35 and 44 years. The median survival was 101.5 months, with some improvement in later years (adjusted HR = 0.83 for 2017-2020). CONCLUSIONS: In countries with well-established population-based screening, CUC is nowadays considered a rare disease. However, it is not considered rare in Bulgaria. Population-based screening starting at an earlier age is the fastest way to improve outcomes.

Endometrial Cancer Individualized Scoring System (ECISS): A machine learning-based prediction model of endometrial cancer prognosis.

OBJECTIVE: To establish a prognostic model for endometrial cancer (EC) that individualizes a risk and management plan per patient and disease characteristics. METHODS: A multicenter retrospective study conducted in nine European gynecologic cancer centers. Women with confirmed EC between January 2008 to December 2015 were included. Demographics, disease characteristics, management, and follow-up information were collected. Cancer-specific survival (CSS) and disease-free survival (DFS) at 3 and 5 years comprise the primary outcomes of the study. Machine learning algorithms were applied to patient and disease characteristics. Model I: pretreatment model. Calculated probability was added to management variables (model II: treatment model), and the second calculated probability was added to perioperative and postoperative variables (model III). RESULTS: Of 1150 women, 1144 were eligible for 3-year survival analysis and 860 for 5-year survival analysis. Model I, II, and III accuracies of prediction of 5-year CSS were 84.88%/85.47% (in train and test sets), 85.47%/84.88%, and 87.35%/86.05%, respectively. Model I predicted 3-year CSS at an accuracy of 91.34%/87.02%. Accuracies of models I, II, and III in predicting 5-year DFS were 74.63%/76.72%, 77.03%/76.72%, and 80.61%/77.78%, respectively. CONCLUSION: The Endometrial Cancer Individualized Scoring System (ECISS) is a novel machine learning tool assessing patient-specific survival probability with high accuracy.

A very rare case of echinococcus granulosus arising in the ovary and the uterus.

Hydatidosis is a zoonosis caused by the larval form of a cestode of the species Echinococcus granulosus, the canine tapeworm. It can affect any organ of the human body except nails, hair, and cornea. It most often involves the liver, lungs, muscles, and bones. Involvement of organs in the small pelvis is extremely rare, mainly secondary to dissemination of hydatidosis from another organ, and the ovaries are most often involved, followed by the uterus. We present a 41-year-old Caucasian woman with complaints of mild pain, heaviness in the small pelvis, and a fibroid detected by ultrasound examination. She had reported for 2 previous operations for echinococcus cysts, and we found cystic formations in the liver and pelvis by computed tomography. It was decided that it is a recurrence of echinococcosis with a new cyst both in ovary and uterus. A hysterectomy with adnexectomy was performed, and one year later there is no evidence of recurrence of echinococcosis. In the presence of a formation in the small pelvis, one should always think about echinococcosis, especially if there is evidence of previous manifestations of the disease. Diagnosing this disease is extremely important for proper treatment. As rare as uterine involvement is, this possibility should not be overlooked.

Papillary Squamotransitional Cell Carcinoma of the Uterine Cervix with Atypical Presentation: A Case Report with a Literature Review.

Introduction: Cervical cancer is the fourth most prevalent malignancy and the fourth leading cause of cancer-related death in women around the world. Histologically, squamous cell carcinoma (SCC) is the most common form of cervical cancer. SCC has several subtypes, and one of the rarest is papillary squamotransitional cell carcinoma (PSCC). In general, PSCC is believed to have a similar course and prognosis to typical SCC, with a high risk of late metastasis and recurrence. Case report: We discuss the case of a 45-year-old patient diagnosed with PSCC who was admitted to our department in December 2021. The clinical manifestations were pelvic discomfort and lymphadenopathy throughout the body. On admission, all laboratory values, with the exception of C-Reactive Protein (CRP) at 22.35 mg/L and hemoglobin (HGB) at 87.0 g/L, were normal. The clinical and ultrasound examination revealed a painful formation with indistinct borders in the right portion of the small pelvis. Following dilation and curettage, a Tru-Cut biopsy of the inguinal lymph nodes was performed. The investigation histologically indicated PSCC. MRI of the small pelvis showed an endophytic tumor in the cervix with dimensions of 35/26 mm and provided data for bilateral parametrial infiltration; a hetero-intensive tumor originating from the right ovary and involving small intestinal loops measuring 90/58 mm; and generalized lymphadenopathy and peritoneal metastases in the pouch of Douglass. The FIGO classification for the tumor was IVB. The patient was subsequently referred for chemotherapy by the tumor board's decision. Discussion: Despite the generally good prognosis of SCC, PSCC is a rare and aggressive subtype. It is usually diagnosed at an advanced stage and has a poor prognosis. Conclusions: PSCC is a rare subtype of SCC, and its diagnosis and treatment are challenging.

Lymphoepithelioma-like Carcinoma of the Breast Synchronous with a High-Grade Invasive Ductal Carcinoma and Ductal Carcinoma in Situ in a Different Quadrant of the Same Breast: A Case Report.

Lymphoepithelioma-like breast carcinoma (LELC) is a rare type of malignant breast tumor that is not included in the current edition of the World Health Organization (WHO) classification of breast tumors. Currently, there are no clearly defined therapeutic strategies, and the general information on breast LELC is based on sporadic clinical cases described in the medical literature. We present a clinical case that describes a 49-year-old woman with a tumor formation in the right breast, histologically verified as LELC, together with a non-palpable, synchronous high-grade invasive ductal carcinoma and ductal carcinoma in situ Grade 2 (DCIS G2) in a different quadrant of the same breast. To our knowledge, this is the first case described in the literature that combines a LELC with a synchronous carcinoma in the same breast.

Re-excision within a radius of 2 cm in patients with melanoma of the skin - sufficient for local oncological radicalness.

Introduction: Malignant melanoma is one of the most malignant tumours in the human body. Radical re-excision of the tumour bed is a principal part of its surgical treatment. We aim to test the hypothesis that the re-excision with a 2 cm margin in all directions to the scar from the previous biopsy of the primary tumour provides sufficient local control in patients with this disease. Material and methods: This is a prospective descriptive study using STROBE methods, including all 151 patients with malignant melanoma of the skin, diagnosed and treated at the Department of Plastic, Reconstructive, and Aesthetic Surgery, Dr Georgi Stranski University Hospital, Medical University of Pleven, Bulgaria, in the period 2012-2016. Twenty-one cases were omitted from the study during the observation period due to lack of sufficient data. The re-excision was mainly within 2 cm margins in all directions to the scar from the previous biopsy of the primary tumour. Results: Data of all 130 patients with malignant skin melanoma, diagnosed and treated at our single large centre, were prospectively registered and analysed. These were 67 male and 63 female patients with a mean age at diagnosis of 61.6 years (range: 17-91 years). Using the re-excision within 2 cm margins, we identified only 1 (0.77%) patient with a histologically confirmed residual tumour in the re-excised flap. Local recurrence was observed in 13 (10%) patients. Conclusions: Re-excision with a 2 cm margin is sufficient to achieve local surgical radicalness in the treatment of this disease without compromising oncological survival.

Standards in surgical training in advanced pelvic malignancy across Europe and beyond - A Snapshot analysis.

INTRODUCTION: Multimodal treatment of patients with advanced pelvic malignancies (APM) is challenging and surgical expertise is usually concentrated in highly specialised centres. Given significant regional variation in APM surgery, surgical training represents a cornerstone in standardising and future-proofing of this complex therapy. The aim of this study was to describe the availability and current satisfaction levels with surgical training for APM. MATERIAL AND METHODS: An online questionnaire was developed and distributed through the Redcap© platform with 32 questions addressing participant and institution demographics, and training in APM surgeries. The survey was electronically disseminated in 2021 to surgical networks across Europe including all specialities treating APM via the European Society of Surgical Oncology (ESSO). All statistical analysis were performed using R. RESULTS: The survey received 280 responses from surgeons across 49 countries, representing general surgery (36%), surgical oncology (30%), gynaeoncology (15%), colorectal surgery (14%) and urology (5%). Fifty-three percent of participants report performing >25 APM procedures/year. Respondents were departmental chiefs (12%), consultants (34%), specialist surgeons (40%) and fellows (15%). 34% were happy/very happy with their training with 70% satisfaction about their exposure to surgical procedures. Respondents reported a lack of standardised training (72%), monitoring tools (41%) and mentorship (56%). 57% rated attended courses as useful for training, while 80% rated visiting expert centres as useful. CONCLUSION: This study has identified a learning need for improved structured training in APM, with low current satisfaction levels with exposure to APM training. Organisations such as ESSO provide an important platform for visiting expert centres, courses, and structured training.

Prognostic Utility of CD47 in Cancer of the Uterine Cervix and the Sensitivity of Immunohistochemical Scores.

INTRODUCTION: Cancer of the uterine cervix (CUC) is still one of the most frequent oncological diagnoses in women. The specific interactions between the tumor cells of CUC and the cells and tissues in the tumor microenvironment can affect cancer cells' invasive and metastatic potential and can modulate tumor's progression and death. CD47 is a trans-membranous immunoglobulin, expressed in many cells. It protects the cells from being destroyed by the circulating macrophages. AIM: We aimed to evaluate the prognostic role of CD47 expressed in the tumor tissues of patients with CUC for tumor progression and to find the most sensitive immunohistochemical score for defining the cut-off significantly associated with tumor biology and progression. MATERIALS AND METHODS: Paraffin-embedded tumor tissues from 86 patients with CUC were included in the study. Clinico-morphological data for patients, such as age and stage at diagnosis according to FIGO and TNM classification, were obtained from the hospital electronic medical records. Immunohistochemical staining was performed with rabbit recombinant monoclonal CD47 antibody (Clone SP279). The final result was interpreted based on three reporting models in immunohistochemistry: H-score, Allred score and combined score. RESULTS: The expression of CD47 was higher in tumors limited in the cervix compared with those invading other structures, and it did not depend on the nodal status. The results of immunohistochemical staining were similar regardless of which immunohistochemical method was used. The most significant correlation with TNM stage was observed with the H-score (p = 0.00018). The association with the Allred and combined score was less significant, with p values of 0.0013 and 0.0002, respectively. CONCLUSION: The expression of CD47 in the cancer cells is prognostic for tumor invasion in the surrounding structures, independent of lymph node engagement. The H-score is the most sensitive immunohistochemical score to describe tumor stage. To the best of our knowledge, this is the first study evaluating the significance of CD47 expression in CUC.

Intraoperative Radiotherapy with Balloon-Based Electronic Brachytherapy System-A Systematic Review and First Bulgarian Experience in Breast Cancer Patients.

(1) Background: We aimed to analyze currently available studies with intraoperative radiotherapy (IORT) as a choice of treatment where the Xoft Axxent® electronic brachytherapy (eBx) system was used as a single-dose irradiation and an exclusive radiotherapy approach at the time of surgery in patients with early breast cancer (EBC). We also compared the results of the systematic review to the Bulgarian experience. (2) Methods and Materials: We performed a systematic review of the studies published before February 2021, which investigate the application of a single-fraction 20 Gy radiation treatment, delivered at the time of lumpectomy in EBC patients with the Xoft Axxent® eBx System. A systematic search in PubMed, Scopus, and ScienceDirect was performed. The results are reported following the PRISMA guidelines. The criteria on patients' selection for IORT (the additional need for EBRT), cosmetic outcomes, and recurrence rate from the eligible studies are compared to the treatment results in Bulgarian patients. (3) Results: We searched through 1032 results to find 17 eligible studies. There are no published outcomes from randomized trials. When reported, the cosmetic outcomes in most of the studies are defined as excellent. The observed recurrence rate is low (1-5.8%). Still, the number of patients additionally referred to postoperative external breast radiotherapy (EBRT) is up to 31%. Amongst the 20 patients treated in Bulgaria, the cosmetic outcomes are also evaluated as excellent, five of which (25%) are referred for EBRT. Within median follow-up of 39 months, there was one local and one distal recurrence. (4) Conclusions: Current evidence demonstrates the Xoft Axxent® eBx system as a safe and feasible technique for IORT delivery in EBC patients. There are no randomized controlled trials conducted at this time point to prove its long-term effectiveness. Better patient selection and a reimbursement strategy have to be proposed to extend the application of this technique in Bulgaria.

LncRNA MORT (ZNF667-AS1) in Cancer-Is There a Possible Role in Gynecological Malignancies?

Gynecological cancers (GCs) are currently among the major threats to female health. Moreover, there are different histologic subtypes of these cancers, which are defined as 'rare' due to an annual incidence of <6 per 100,000 women. The majority of these tend to be associated with a poor prognosis. Long non-coding RNAs (lncRNAs) play a critical role in the normal development of organisms as well as in tumorigenesis. LncRNAs can be classified into tumor suppressor genes or oncogenes, depending on their function within the cellular context and the signaling pathways in which they are involved. These regulatory RNAs are potential therapeutic targets for cancer due to their tissue and tumor specificity. However, there still needs to be a deeper understanding of the mechanisms by which lncRNAs are involved in the regulation of numerous biological functions in humans, both in normal health and disease. The lncRNA Mortal Obligate RNA Transcript (MORT; alias ZNF667-AS1) has been identified as a tumor-related lncRNA. ZNF667-AS1 gene, located in the human chromosome region 19q13.43, has been shown to be silenced by DNA hypermethylation in several cancers. In this review, we report on the biological functions of ZNF667-AS1 from recent studies and describe the regulatory functions of ZNF667-AS1 in human disease, including cancer. Furthermore, we discuss the emerging insights into the potential role of ZNF667-AS1 as a biomarker and novel therapeutic target in cancer, including GCs (ovarian, cervical, and endometrial cancers).

An Overview of the Role of Long Non-Coding RNAs in Human Choriocarcinoma.

Choriocarcinoma (CC), a subtype of trophoblastic disease, is a rare and highly aggressive neoplasm. There are two main CC subtypes: gestational and non-gestational, (so called when it develops as a component of a germ cell tumor or is related to a somatic mutation of a poorly differentiated carcinoma), each with very diverse biological activity. A therapeutic approach is highly effective in patients with early-stage CC. The advanced stage of the disease also has a good prognosis with around 95% of patients cured following chemotherapy. However, advancements in diagnosis and treatment are always needed to improve outcomes for patients with CC. Long non-coding (lnc) RNAs are non-coding transcripts that are longer than 200 nucleotides. LncRNAs can act as oncogenes or tumor suppressor genes. Deregulation of their expression has a key role in tumor development, angiogenesis, differentiation, migration, apoptosis, and proliferation. Furthermore, detection of cancer-associated lncRNAs in body fluids, such as blood, saliva, and urine of cancer patients, is emerging as a novel method for cancer diagnosis. Although there is evidence for the potential role of lncRNAs in a number of cancers of the female genital tract, their role in CC is poorly understood. This review summarizes the current knowledge of lncRNAs in gestational CC and how this may be applied to future therapeutic strategies in the treatment of this rare cancer.

Adenosquamous Carcinoma of the Uterine Cervix - Impact of Histology on Clinical Management.

INTRODUCTION: Historically, the incidence rate of cervical cancer (CC) in Eastern Europe and particularly in Bulgaria has constantly been higher than that in the other European countries. Adenosquamous carcinoma (ASC) is a rare histological subtype of CC with incidence rate of less than 6 per 100,000. We aimed to analyze the epidemiology and prognosis of all Bulgarian patients with ASC, registered at the Bulgarian National Cancer Registry (BNCR), and to compare patients' characteristics and outcomes with those of patients, treated at a large specialized institution - the Department of Gynecologic Oncology, University Hospital in Pleven, Bulgaria. MATERIALS AND METHODS: This is a retrospective study of all cases of ASC, registered at the BNCR for a 10-year period of time. The Kaplan-Meier analysis with Log rank test was used to estimate the significant differences. RESULTS: The incidence rate of ASC was calculated as 3.2% of all CC registered in BNCR and 4.97% of all stage I patients, treated in our department. The 5-year overall survival (OS) rate of all patients with ASC tumors from the registry was 50.5%. A total of 171 (48.4%) of the patients had T1 tumors and a 5-year OS of 67.1%. Lymph node status was a significant prognostic factor for OS (p=0.001). Thirty-one patients with T1 tumors and ASC histology were treated in our department for the same period of time. Lymph node metastases were found in 10 of them (32.2%). The 5-year observed OS in ASC group was 74.19%. CONCLUSION: The histological subtype of cancer of the uterine cervix has an impact on prognosis and should not be simply considered as a descriptive characteristic but a poor prognostic feature and should be an integral part of the decision-making in clinical management of patients.