OVEREXPRESSION OF HER2/NEU ONCOGEN, P53 AND ESTROGEN RECEPTOR IN ENDOMETRIAL HYPERPLASIA AND CARCINOMA
AbstractBackground: Endometrial hyperplasia with its two types (simple and complex hyperplasia with or without atypia) is one of the most important endometrial lesions. The probability of progression of endometrial hyperplasia to carcinoma is related to the degree of architectural and/or cytological atypia. There are two fundamentally different pathogenic types of endometrial carcinoma: type I (estrogen related, endometrioid type) and type II (non-estrogen related, non-endometrioid type). Recently, various biomarkers detect prognostic factors in endometrial carcinomas, such as Her2/neu, P53 as well as Estrogen Receptor (ER).
Materials and Methods: During the period from November 2015 to May 2016, 101cases (as blocks) were collected from the archive of different Laboratories. There were 52 cases of endometrial hyperplasia; the other 49 cases were endometrial carcinoma. All the cases were revised histologically (using Hematoxylin and Eosin stain) to identify the types of hyperplasia and carcinoma, as well as the grade of carcinoma and the degree of myometrial invasion. Three markers were applied (Her2/neu, P53 and Estrogen Receptor) by using automated immunohistochemistry staining.
Results: The predominant cases of the endometrial hyperplasia were in the 5th decade with a mean age (44.6) years. The majority were simple hyperplasia without atypia. The endometrial carcinoma cases were predominant in the 6th decade with a mean age (55.5) years. The majorities were of the classical type (65.3%) and grade II (48.9%). Her2/neu expression significantly increased in positivity (p=0.001), while P53 did not show significant changes with disease progression (p= 0.1). Estrogen Receptor immunoreactivity was decreased significantly from simple hyperplasia to carcinoma (p= 0.001). There were no correlation between these triple markers and increasing grade. Although, the number of cases showed more positivity of Her2/neu and P53 with the increasing of myometrial invasion and expression of Estrogen receptor decreased but the relation was statistically not significant (p= 0.9). Among the studied cases, there were 18.2% and 50% of complex hyperplasia without atypia and atypical hyperplasia respectively transmitted to carcinoma, while none of the simple hyperplasia cases showed transmission to carcinoma.
Conclusions: Cases of the endometrial hyperplasia were more prevalent at pre and perimenopausal period while endometrial carcinoma was more prevalent in postmenopausal women. Her2/neu showed more immunoreactivity with progression of the pathological change (increasing morphological and cytological complexity) from endometrial hyperplasia to carcinoma in contrast to Estrogen Receptor expression which showed converse relationship with progression of the disease. Expression of P53 was seen to have more immunoreactivity with high grade and highly invasive tumor
Al-Bader Maie, Ford Christopher, Al-Ayadhy Bushra, Francis Issam (2011). Analysis of estrogen receptor isoforms and variants in breast cancer cell lines. Experimental and Therapeutic; 2 (3):537-544.
Aparna A, Donna C, William M et al. (2009). EphA2 overexpression is associated with lack of hormone receptor expression and poor outcome in endometrial cancer. Cancer; 115(12): 2684-2692.
Bozdoğan Ö, Atasoy P, Erekul S et al. (2002). Apoptosis-Related Proteins and Steroid Hormone Receptors in Normal, Hyperplastic, and Neoplastic Endometrium. International Journal of Gynecological Pathology; 21(4): 375-382.
Cai H, Yun-feng Z, Bi-cheng W, Ling-ling G (2008). Expression of estrogen receptors and protein in endometrial carcinoma. Cancer Therapy; 6: 907-912.
Catasús L, Gallardo A, Cuatrecasas M Prat J (2009). Concomitant PI3K-AKT and p53 alterations in endometrial carcinomas are associated with poor prognosis. Modern Pathology; 22(4):522-529.
Erdem O, Erdem M, Dursun A et al. (2003). Angiogenesis, p53, and bcl-2 expression as prognostic indicators in endometrial cancer: Comparison with traditional clinicopathologic variables. International Journal of Gynecological Pathology; 22(3):254-260
Galic Vijaya, Schiavone Maria, Herzog Thomas, Holcomb Kevin et al. (2013). Prognostic Significance of Mucinous Differentiation of Endometrioid Adenocarcinoma of the Endometrium. Cancer Investigation; 31(7):500-508.
Gargi R (2013). Endometrial Hyperplasia: A Clinicopathological Study in a Tertiary Care Hospital. The Journal of Obstetrics and Gynecology of India; 63(6): 394–398.
Goto T, Takano M, Aoyama T et al. (2012). Prognosis of high-grade endometrial cancer: a comparison of serous-type and clear cell type to grade 3 endometrioid-types. European Journal of Gynecological Oncology; 33(6):579-583.
Ilie D, Georgescu CV, Simionescu C (2011): "Immunohistochemical Aspects of Endometrium Hyperplasia in Perimenopause". Current Health Sciences Journal; 37(2):20-67.
Ilyés L, Rădulescu C, Grama O et al. (2011) Overexpression of HER2/neu Receptor–Prognostic Factor in Endometrial Cancer. Acta medicine marissiensis; 57(5):55-62.
Kumar V, Cotran S, Robbins L (2003). Robbins basic pathology-7th edition. Philadelphia: Saunders. 691-694.
Lacey J V, Ioffe Jr, B M Ronnett, B Rush et al. (2008). Endometrial carcinoma risk among women diagnosed with endometrial hyperplasia: the 34-year experience in a large health plan. British Journal of Cancer; 98: 45–53.
Lacey J, Chia M (2009). Endometrial hyperplasia and the risk of progression to carcinoma. Maturitas; 63(1):39–44.
Maliheh A, Giti N, Seyyedeh K (2014). Comparison of Crude and Age-Specific Incidence Rates of Breast, Ovary, Endometrium and Cervix Cancers in Iran, 2005. Asian Pacific Journal of Cancer Prevention; 15 (6): 2461-2464.
Mariani Andrea, Sebo Thomas , Katzmanna Jerry et al. (2005). HER-2/neu Overexpression and Hormone Dependency in Endometrial Cancer: Analysis of Cohort and Review of Literature. ANTICANCER RESEARCH ; 25: 2921-2928.
Morrison C, Cohn DE, Zanagnolo V et al. (2006). HER-2 is an independent prognostic factor in endometrial cancer: association with outcome in a large cohort of surgically staged patients. Journal of Clinical Oncology; 24(15):2376-2385.
Okuda Tsuyoshi, Sekizawa Akihiko, Purwosunu Yuditiya et al. (2010). Genetics of Endometrial Cancers. Obstetrics and Gynecology International; 13: 3-8.
Osz J, Yann B, Carole P et al. (2012). Structural basis for a molecular allosteric control mechanism of cofactor binding to nuclear receptors. Proceeding of the National Academy of Science; 109(10): 588-594.
Pieczyńska B, Szymon W, Anton Ż et al. (2011). Analysis of PTEN, estrogen receptor and progesterone receptor expression in endometrial hyperplasia using tissue microarray. Polish Journal of Pathology; 3: 133-138.
Ragni N, Simone F, Federico P et al. (2005). The association between p53 expression, stage and histological features in endometrial cancer. European Journal of Obstetrics, Gynecology and Reproductive Biology; 123(1): 111–116.
Srijaipracharoen S, Tangjitgamol S, Tanvanich S, Manusirivithaya S et al. (2010). Expression of ER, PR, and Her-2/neu in endometrial cancer: a clinicopathological study. Asian Pacific Journal of Cancer Prevention; 11(1):215-20.
Takreem A, Nargis D, Sadia R (2009). Incidence of endometrial hyperplasia in 100 cases presenting with polymenorrhagia in premenopausal women. Journal of Ayub Medical College, Abbottabad; 21(2):60-63
Uchikaw J, Tanri S, Hsien-Chang S et al. (2003). Expression of steroid receptor coactivators and corepressors in human endometrial hyperplasia and carcinoma with relevance to steroid receptors and Ki-67. Cancer expression; 98(10):2207–2213.
Vogelstein B, Lane D, Levine A (2000). Surfing the p53 network. Nature; 408: 307–310.
It is the policy of the Journal of Duhok University to own the copyright of the technical contributions. It publishes and facilitates the appropriate re-utilize of the published materials by others. Photocopying is permitted with credit and referring to the source for individuals use.
Copyright © 2017. All Rights Reserved.