Differences in Clinical and Biological Features Between Type I and Type II Tumors in FIGO Stages I-II Epithelial Ovarian Carcinoma

Autor: Ingiridur Skirnisdottir, Helena Åkerud, Tomas Seidal
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: International Journal of Gynecological Cancer
ISSN: 1525-1438
1048-891X
Popis: Epithelial ovarian cancer (EOC) is still the leading cause of death among women with gynaecological malignancies.1 Based on histopathology and molecular genetic alterations, ovarian carcinomas are divided into 5 main histological types.2 Furthermore, on the basis of morphologic and molecular genetic studies, the 5 types of ovarian cancer can be classified into 2 groups designated types I and II tumors. Thus, type I tumors are composed of low-grade serous (grade 1), low-grade endometrioid (grade 1 or 2), mucinous, and clear cell carcinomas. Type II tumors consist of high-grade serous (grade 2 or grade 3) and high-grade endometrioid (grade 3).3,4 Type I tumors often present in early stage and are slowly growing from benign cystic neoplasm through borderline tumor. They are relatively stable genetically and rarely harbor TP53 mutations with exception of concomitant KRAS mutations in low-grade mucinous tumors.5 In contrast, type II tumors are rapidly growing and more often present in advanced stage. They are genetically highly unstable and have a high frequency of TP53 mutations. There is mounting evidence that types I and II ovarian tumors develop along different molecular pathways.4,6 Some differences in clinical aspects between types I and II tumors have been noted.1 The classic clinicopathological factors have been proven insufficient to define prognostic subgroups.7 It is now widely accepted that cancer can arise as a cell cycle defect, but cellular homeostasis is regulated by proliferation, growth arrest, and apoptosis.8,9 Apoptosis is a biological process controlled by different regulators and potentially could be a goal for new cancer treatment approaches.10 As a transcription factor, wild-type p53 can limit cell proliferation after DNA damage by arresting the cell cycle or inducing apoptosis through the mitochondrial pathway by activating the expression of bax and PUMA.11 However, certain mutants of p53 can inhibit the proapoptotic function of p53 through the formation of heterotetramer with wild-type p53 and induce oncogenesis after up-regulation of C-MYC (Fig. ​(Fig.11).12 PTEN is a main tumor suppressor and induces apoptosis by up-regulation of wild-type p53.13 The cell cycle regulators p21 and p27 are belonging to 1 (the Cip/kip family) of the 2 major families regulating the cell cycle.14 The p21 gene is the primary mediator of p53-induced cell cycle arrest, and cells lacking functional p53 express only low levels of p21.10 FIGURE 1 Wild p53 has important function for both cell cycle arrest and apoptosis. However, certain mutants of p53 can inhibit the proapoptotic function of p53 through the formation of heterotetramer with wild-type p53 and induce oncogenesis after up-regulation ... The primary aim of this study was to compare some clinicopathological features and differences in the immunohistochemical (IHC) profile for the apoptosis regulators p53, C-MYC, bax, PUMA, and PTEN and the cell cycle regulatory proteins p21 and p27, detected in previous studies,15–18 between the groups of types I and II tumors in patients with International Federation of Gynecology and Obstetrics (FIGO) stages I-II ovarian carcinoma.
Databáze: OpenAIRE
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