Specific features of proliferation and apoptosis in non-invasive adenocarcinoma of endometrium and adenocarcinoma with invasion into myometrium
DOI:
https://doi.org/10.14739/2310-1237.2014.1.25957Keywords:
Сarcinoma of Endometrium, Neoplasm Invasiveness, Cell Proliferation, ApoptosisAbstract
Introduction. The development of tumors occurs as a multistage process, where each step corresponds to certain genetic changes of cells and it is a reflection characteristic of different histological forms of cancer. This usually multiple changes include the expression of several oncogenes and inactivation of two or more suppressor genes. Such events are a critical step in the transformation of normal cells into malignant. It is known that the pathogenesis of cancer of the endometrium is the imbalance result of the proliferative and apoptotic processes. Therefore it is particularly important to gain in-depth pathomorphological study of uterine mucosa from cellular and molecular determination of prognosis of tumors that includes immunohistochemical (IHC) diagnostic markers of proliferative activity and apoptosis processes. These studies are aimed to differential diagnosis of invasive and non-invasive adenocarcinomas of the endometrium (AE).
Aim of investigation is the study of proliferative and apoptotic activity in the cells of non-invasive adenocarcinoma of endometrium and adenocarcinoma with invasion into myometrium with an attention to the invasive zone.
Materials and methods. The complex pathomorphological research and immunohistochemical study were provided in histological specimens of operative material of 104 women aged from 41 up to 80 years with non-invasive adenocarcinoma of endometrium and invasive adenocarcinoma with invasion into myometrium. The immunohistochemical study was performed with an indirect immunoperoxidase method in formalin-fixed, paraffin-embedded endometrium specimens obtained from 30 (28,85%) women with non-invasive adenocarcinoma, 30 (28,85%) women with adenocarcinoma with invasion into myometrium and 44 (42,3%) women with adenocarcinoma with invasion into myometrium, in which directly zone of myometrial invasion was studied. IHC study was performed using antibodies Mo a-Hu Ki-67 Antigen, Clone MIB-1, Mo a-Hu p53 Protein, Clone DO-7,Mo a-Hu Bcl-2 Oncoprotein Clone 124, WAF 1 Antibody 3. Clone DCS 60.2 and Mo a-Hu Caspase Ab-3, Сlone 3CSP03 and visualization system DAKO EnVision+ with diaminobenzidine. Endometrial tissues of 20 gynecologically healthy women were used as samples for test-control.
Results. The high expression of cell proliferation marker Ki-67 was found in non-invasive and invasive AE (3,3 ± 0,08 points in the noninvasive AE and 3,5 ± 0,07 points in the invasive AE). Invasive adenocarcinoma of the endometrium differs from AE without invasion of the myometrium in significantly higher levels of expression of p53 gland epithelium (index of labeled nuclei was 19,77±3,11% in the invasive AE vs 11,06±0,27% in the form of non-invasive tumor, p <0,05). In comparative IHC analysis high expression of inhibitor of cyclin-dependent kinases r21WAF in gland epithelial cells was identified both in non-invasive and invasive adenocarcinoma of the endometrium. It was established that adenocarcinoma of the endometrium without myometrial invasion differs from invasive AE also in significantly higher levels of expression of caspase-3 (58,09±4,52% of cells in the invasive AE vs. 48,55±6,3% of cells in AE without invasion). In women with invasive adenocarcinoma of the endometrium low expression of apoptosis inhibitor bcl-2 in numerically small epitheliocytes of glands and in stroma lymphocytes is determined, it is almost twice significantly lower than in adenocarcinoma of the endometrium without myometrial invasion (p<0.05). The level of Ki-67 expression in tumor cells of invasive zone was lower than in the main mass of adenocarcinoma, and levels of p53 and caspasa-3 expression in these two zones were the same.
Conclusions. Invasive adenocarcinoma of the endometrium differs from adenocarcinoma without invasion into the myometrium in significantly higher levels of nuclear expression of Ki-67, p53 and cytoplasmic expression of caspase-3 by atypical epithelium of glands and almost twice lower expression of bcl-2. And these two groups of adenocarcinomas have the same high level of p21WAF1 expression.
References
Chernyshova, A. L., Kolomiets, L. A., Bochkareva, N. V., & Kritskaya, N. G. (2010) Immunogistohimicheskie kriterii prognoza pri rake e`ndometrija [Immunohistochemical prognostic criteria for endometrial cancer]. Sibirskij onkologicheskij zhurnal,1(37), 79–84. [in Russian].
Pozharisskij, K. M., Samsonova, E. A., & Ten, V. P. (2005) Immunogistokhimicheskij profi l’ e`ndometrioidnoj adenokarcinomy tela matki: ER, PR, HER-2, Ki-67 i ikh prognosticheskoe znachenie [Imunohistochemical profi le endometrial adenocarcinoma of the uterus ER, PR, HER-2, Ki 67 and their prognostical meaning]. Arkhyv patolohyy, 2, 13 17. [in Russian].
Risberg, B., Karlsson, K., Abeler, V., Lagrelius, A., Davidson, B., & Karlsson, M. G. (2002). Dissociated Expression of Bcl-2 and Ki-67 in Endometrial Lesions: Diagnostic and Histogenetic Implications. International Journal of Gynecological Pathology, 21(2), 155–160.
Ioachim, E., Kitsiou, E., Mitselou, A., Zagorianakou, N., Charalabopoulos, K., Salmas, M., et al. (2003) p21(WAF1/Cip1) protein expression in normal, hyperplastic and malignant endometrium. Correlation with hormone receptor status, C ERBB 2 oncoprotein, BCL 2 and other cell cycle related proteins (RB, P53, Ki 67, PCNA). Experimental Oncology, 25(3), 200–205.
Nordström, B., Strang, P., Bergström, R., Nilsson, S., & Tribukait, B. (1996). A comparison of proliferation markers and their prognostic value for women with endometrial carcinoma: Ki-67, proliferating cell nuclear antigen, and fl ow cytometric S-phase fraction. Cancer, 78(9), 1942–1951.
Kyselev, V. Y, Lyashhenko, A. A. (2005) Molekulyarnye mekhanizmy regulyacii giperplasticheskikh processov [Molecular mechanisms of regulation of hyperplastic processes]. Moscow: Dimitrejd Grafik Grupp. [in Russian].
Dallenbach-Hellweg, G., Schmidt, D., Dallenbach-Hellweg, G., & Dallenbach, F. (2010) Atlas of Endometrial Pathology. Berlin, Heidelberg: Sprienger.
Pallazo, J. P., Mercer, W. E., Kovatich, M. S., & Hugh, M. (2004) Immunohistochemical localization of p21 WAF1/Cip1 in Normal, Hyperplastic, and Neoplastic Uterine Tissues. Human Pathol, 28(1), 60–66.
Buchynska, L. G., & Nesina, I. P. (2006) Expression of the cell cycle regulators p53, p21WAF1/CIP1 and p16INK4A in human endometrial adenocarcinoma. Experimental Oncology, 28(2), 152–155.
Porichi, O., Nikolaidou, M. E., Apostolaki, A., Tserkezoglou, A., Arnogiannaki, N., Kassanos, D., et al. (2009) Panotopoulou E. BCL-2, BAX and P53 expression profi les in endometrial сarcinoma as studied by real-time PCR and іmmunohistochemistry. Anticancer Res, 29, 3977–3982.
Downloads
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (SeeThe Effect of Open Access).
