MOLECULAR CHARACTERISTICS AND PROGNOSTIC MARKERS IN ENDOMETRIAL INTRAEPITHELIAL NEOPLASIA (CRITICAL REVIEW)

Endometrial carcinoma represents the most common gynaecologic malignancy, which frequently arises from malignant progression of endometrial intraepithelial neoplasia (EIN). Nowadays, there are no defined prognostic markers for the prognosis of the malignant progression of EIN and it still represents the subject of various investigations. Different studies indicate, that sex hormone receptors, DNA damage and apoptosis proteins, as well as epithelial-mesenchymal transformation markers play an important role in the progression of EIN. However, most of the published studies are full of contradictory results, which indicates that additional studies are necessary. In current review, we will discuss the current knowledge about the mentioned markers in terms of the prognosis of EIN.</jats:p

Molecular features of endometrial metaplastic processes, the risk factors for cancer relapse and neoplastic transformation

Endometrial Metaplasia is the process in which normal endometrioid glands are undergoing replacement by other types of benign epithelium. Endometrium can show us a diversity of metaplastic changes. Modified differentiation of Endometrial cells can be due to the presence of degenerative/reparative, hormonal or neoplastic processes. The presence of Epithelial Metaplasia can signify other concomitants benign and malignant processes. Endometrial metaplasia can be either a single process or present with other histopathological changes. There are different types of endometrial metaplasia but the most common is tubal metaplasia. The second most common can be squamous metaplasia, transitional cell metaplasia, arias-Stella reaction/changes, cellular eosinophilic changes and mucinous metaplasia. different types of metaplasia can show us the various type and intensities of expression for P16, Cyclin E, Cyclin A, Ki67, B catenin, ER, CDX2, CD10, P63. The role and importance of distinct types of endometrial metaplasia in the relapse of cancer and neoplastic progression are still unknown. There is the clinical opinion that behind every single metaplastic process there is stem cell reprogramming but the phenomenon of endometrial metaplasia needs more thorough studies.</jats:p

PROBLEMATIC ISSUES IN THE EVALUATION OF MOLECULAR CHARACTERISTICS AND POTENTIAL NEOPLASTIC TRANSFORMATION OF CERVICAL METAPLASIA

Metaplasia represents the replacement of one differentiated cell type with another differentiated cell type, which is frequently seen in uterine cervix, particularly in endocervical epithelium. There are many different types of metaplasia in endocervix. It is suggested that metaplasia represents the fertile soil for the development of neoplasia. However, which cases of metaplasia transform into neoplasia, which type of metaplasia is more realted to neoplastic transformation or if there are some molecular markers which can predict the potential of neoplastic transformation, are nowadays less known. Current review represents the critical discussion of the available literature with regards to the evaluation of molecular markers and the potential of neoplastic transformation in cervical metaplasia.</jats:p

PROBLEMATIC ISSUES IN THE EVALUATION OF PHENOTYPIC PROGNOSTIC MARKERS IN OVARIAN GERM-CELL TUMORS

Ovarian germ-cell tumors represent about 15-20% of all ovarian tumors. They are characterised with high histological and clinical heterogeneity. Ovarian germ-cell tumors can be both benign and malignant. Nowadays, the prognostic markers of ovarian germ-cell tumors are less studied. In particular, there is only limited information about the phenotypic determinants of the malignant transformation of benign germ-cell tumors, as well as lack of information about the relapse development after treatment of malignant germ-cell tumors. In presented review article, the detailed cahracteristics of ovarian germ-cell tumors and the problematic issues in the determination of their prognostic features are discussed.</jats:p

Molecular features of tubo-ovarian epithelial changes in ovarian epithelial tumours

The etiology and pathogenesis of ovarian serous carcinomas as well as prognoses and clinical management are still under vigorous research. The data provided by many studies support the idea that ovarian serous carcinomas are mainly influenced by the changes occurring in the fallopian tube epithelium. This theory is supported by molecular lesions present in high-grade ovarian cancers and fallopian tube neoplasms. This topic needs some additional studies using pathogenetic characteristics like proliferative and apoptotic changes, which will further support and even may take it under suspicious the theory that ovarian carcinomas are originating from the fallopian tube. It is also crucial to study hormonal expressions while there is a lot of information that steroid hormones have a huge role in the pathogenesis of ovarian carcinomas but there is almost very little data on how these influences are related to the fallopian tube neoplasms. A deeper understanding of ovarian tumours and their etiological pathways are important to prevent and determine prognoses, which will enable better therapeutic methods. It has utmost importance to study additional characteristics like stem cell distribution in the fallopian tube epithelium and in ovarian neoplasms. The cancer heterogeneity need also further discussion regarding ovarian cancer novel classifications. This will finally aid the modification of better-personalized treatment.</jats:p

The role of the microbiome in the contribution of progression in cervical neoplasms

The microbiome plays a crucial role in controlling viral infections like the Human Papillomavirus. Getting infected by HPV is not always necessary or not sufficient for the progression of cervical cancer. According to many kinds of research, it was shown that the presence of Human papillomavirus infection is not always connected to the abundance of Lactobacilli and L. gasseri. Besides that some research data suggests an association of cervicovaginal microbiome to viral infections, there are very few things clear about the exact role of the microbiome in carcinogeneses and also about mechanisms and consequences, which are responsible for the HVP persistence and elimination. Recently there are invoked some theoretical models about the Virus-Bacteria-host organism interaction and virus-associated neoplasms are classified into five major types. The characteristics, features and variability of how the cervical epithelial cells maintain to discover various types of pathogen configuration receptors are still under research such as pathogen configuration detection receptors toll-like receptor family (TLR), Retinoic acid-inducible gene 1 (RIG-1) and Nod-like receptor family (NOD). There is a lot more to study thoroughly about how all of these receptors are functioning in virus inducible lesions and what kinds of influences do they have on virus persistence and neoplastic progression</jats:p

Phenotypic features of the immune microenvironment in ovarian epithelial neoplasms and its role in tumour progression

The tumour is characterised by the presence of various amounts of lymphocytic infiltration, which is seen in different areas of cancer and has not only prognostic value the predictive value as well. Tumour-infiltrating lymphocytes (TILs) in ovarian cancer can be associated either with good prognoses or bad prognoses in some cases. The constituent which makes the tumour immune microenvironment is still under vigorous research while they may have the potential to be well modified predictive and prognostic values in ovarian cancer. The data provided by already conducted research are controversial which suggests the need for further deeper studies. Besides this fact, there is no clear determination which histological subtype of ovarian cancer is under research or in many cases all of the morphological types are united. All of these facts mentioned can clarify why the results of many pieces of research provide controversial information. It is crucial that the immune microenvironment of various morphological subtypes of ovarian carcinomas be studied separately and individually.</jats:p