Microsatellite Instability (MSI) as Genomic Marker in Endometrial Cancer: Toward Scientific Evidences

Abstract

Endometrial Cancer is the most frequent tumor in western world nations, with 142,000 new cases each year and 42,000 casualties. This form of cancer typically affects women between 55 and 65 years of age, and ranks fourth among female tumors. Endogenous predisposing conditions to endometrial cancer development are: late menopause, early menarche and hyperestrogenism, while hormone replacement therapy, obesity, alcohol, diabetes, and a diet rich in animal fats as well as chronic liver disease, are the exogenous factors. This tumor may also have an hereditary predisposition, as in the Lynch Syndrome or in HNPCC (Hereditary NonPolyposis Colorectal Cancer), since genetic modifications induced by the "MisMatch Repair" genes lead to a tumoral development susceptibility, not only in the colon. The phenotypical consequences of these genetic modifications may be found in the microsatellite instability (MSI) and in the loss of heterozygosity (LOH), which generate the replication errors in positive phenotypes repeats. These express the incapability to repair short nucleotide insertions or deletions, generated by a wrong DNA replication. Due to such genetic modifications, new allelic variants arise in the endometrial tissue, confirming the high degree of this genetic disorder. Recent studies showed that the MSI and LOH in endometrial cells may be associated with the possible loss in the expression of cellular control and with the possible degeneration of the cell growth phenomenon. There is also a possibility of utilizing these new genetic markers in the endometrial mucosa to study these tissues and to detect any possible neoplastic transformations, thanks to Genomics.

Prevention of lymphocele in female pelvic lymphadenectomy by a collagen patch coated with the human coagulation factors: A pilot study

“…Other histological types tend to have a poorer prognosis, since they are more aggressive (high grade ¼ G3) and present at a more advanced FIGO stage. These include clear cell and serous carcinomas [2].…”

“…Endometrial cancer spreads directly into surrounding tissues, such as corpus uteri and cervix, but disease spread also occurs via lymphatic vessels. Lymphatic drainage of the womb is primarily via the pelvic lymph nodes, which surround the external and common iliac vessels, and then on to the para-aortic lymph nodes [2].…”

Lymphocele Prevention After Pelvic Laparoscopic Lymphadenectomy by a Collagen Patch Coated With Human Coagulation Factors: A Matched Case-Control Study

“…1 Most patients with endometrial cancer present with early disease (International Federation of Gynecology and Obstetrics [FIGO] stage I), where the disease is confined to the uterus. 2 The lymphatic drainage of the uterine corpus is complex, with a bilateral and a bipartite lymphatic pathway. The lower uterine segment drains to the pelvic lymph nodes via the broad ligaments, parametria, and paracervical pathway; the upper segment of the uterine corpus drains into the paraaortic lymph nodes via the infundibulopelvic ligaments.…”

Microsatellite instability analysis in uterine cavity washings as a screening tool for endometrial cancer in Lynch syndrome

“…Indeed, MSI can be observed in endometrial cancer, but is never found in normal endometrium, even in LS patients [10]. In cancer cases, there is an association between the absence of expression of either MLH1 or MSH2, the presence of germline mutations in the hMLH1 and hMSH2 genes, and the existence of tumor MSI [13]. In a case report, MSI and loss of expression of a MMR protein were found in endometrial hyperplasia without atypia 7 months before the diagnosis of endometrial cancer, suggesting that DNA repair defect appears early in the carcinogenesis process [14].…”