Aksiller lenf nodu metastazlı invaziv duktal meme karsinomda E-cadherin, p53, c-erb-B2 (HER- 2/neu) ve steroid reseptörleri (ER, PgR) ekspresyonu arasındaki ilişki

Year 2015, , 99 - 104, 14.09.2015

Nihal Kılınç

https://doi.org/10.5472/MMJoa.2802.07

Abstract

Amaç: Aksiller lenf nodu metastazlı invaziv duktal meme karsinomda E-cadherin, p53 tümör supressör gen, c-erbB-2 (HER2/neu) ve steroid reseptörleri (ER ve PgR) ekspresyonu arasındaki ilişkiyi araştırmak amaçlanmıştır.Hastalar ve Yöntem: Bu çalışmada, 30 aksiller lenf nodu metastazlı ve 30 aksiller lenf nodu metastazı mevcut olmayan invaziv duktal meme karsinomlu 60 hasta immunokimyasal metodu kullanılarak E-cadherin ve c-erbB-2, ER ve PgR antikorları değerlendirildi.Bulgular: İnvaziv duktal meme karsinomlu 60 hastanın 39’unda (%65) E-cadherin ile boyanma tesbit edilmedi. Sırasıyla ER, PgR, p53, ve c-erb-B2, 60 hastanın 36’ında (%60), 60 hastanın 26’ında (%43,3), 60 hastanın 33’ünde (%55), and 60 hastanın 29’unda (%48,3) pozitif boyanma görüldü. PgR ve c-erb-B2 boyanması lenf nodu metastazı ile ilişkili idi (sırasıyla, p=0,009, p=0,001). E-cadherin proteini ile yaş arasında ilişki görülmedi. E-cadherin ile lenf nodu metastazı ve p53 arasında ilişki görüldü (sırasıyla, p

Keywords

Meme karsinomu, E-cadherin, p53, c-erb-B2, ER, PgR Metastaz

Relation between the expression of E-cadherin, p53,c-erb-B2 (HER-2/neu) and steroid receptors (ER, PgR) in invasive ductal breast carcinoma with axillary lymph node metastases

Abstract

Objective: This study explores the correlation between the expression of E-cadherin, p53 tumor suppressor gene, c-erb-B2 (HER-2/neu) and steroid receptors (ER, PgR) in invasive ductal breast carcinoma with axillary lymph node metastases.

Patients and Methods: We have investigated tumor samples from sixty patients with invasive ductal breast carcinoma. 30 of the patients had axillary lymph node metastases and 30 had no axillary lymph node metastases. Tumor tissues of these patients were evaluated by immunohistochemistry for E-cadherin, p53, c-erb-B2 (HER-2/neu) and steroid receptors (ER, PgR). 

Results: E-cadherin staining was not expressed in 39 patients (65%) with invasive ductal breast carcinoma. ER, PgR, p53, and c-erb-B2 signals were positive in 36 (60%), 26 (43.3%), 33 (55%), and 29 (48.3%) of the patients, respectively. PgR and c-erb-B2 expression was associated with lymph node metastases (p=0.009, p=0.001, respectively). No association was found between the reduced E-cadherin protein and age. The presence of E-cadherin was associated with axillary lymph node metastases and p53 (p<0.009, p<0.001, respectively).

Conclusion: We found that, the p53 protein may play a role in regulation of E-cadherin protein expression in invasive ductal breast carcinomas with axillary lymph node metastases.

Keywords

Breast carcinoma, E-cadherin, p53, c-erb-B2, ER, PgR, Metastases

References

• 1. Park D, Karesen R, Ulrika A, Noven T, Sauer T. Expression pattern of adhesion molecules (E-cadherin, alpha-, beta-, gamma-catenin and c1audin-7), their influence on survival in primary breast carcinoma, and their corresponding axillary lymph node metastasis. APMIS 2007;115:52-65. doi: 10.1111/ j.1600-0463.2007.apm_524.x
• 2. Kovacs A, Dhillon J, Walker R A. Expression of P-cadherin, but not E-cadherin or N-cadherin, relates to pathological and functional differentiation of breast carcinomas. Mol Path 2003;56:318-22. doi:10.1136/mp.56.6.318
• 3. Mohammadizadeh F, Ghasemibasir H, Rajabi P, Naimi A, Eftekhari A, Mesbah A. Correlation of E-cadherin expression and routine immunohistochemistry panel in breast invasive ductal carcinoma. Cancer Biomark 2009;5:1-8. doi: 10.3233/ CBM-2009-0551
• 4. Singhai R, Patil VW, Jaiswal SR, Patil SD, Tayade MB, Patil AV. E-Cadherin as a diagnostic biomarker in breast cancer. North Am J Med Sci 2011;3:227-33. doi.org/10.4048/ jbc.2013.16.1.16
• 5. Bukholm IK, Nesland JM, Karesen R, Jacobsen U, BorresenDale AL. Expression of E-cadherin and its relation to the p53 protein status in human breast carcinomas. Virchows Arch 1997; 431:317-21. doi: 10.1007/s004280050105.
• 6. Kilinc N, Yaldiz M. p53, c-erbB-2 expression and steroid hormone receptors in breast carcinoma: correlations with histopathological parameters. Eur J Gynaecol Oncol 2004;25:606-10.
• 7. Yao ZX, Lu LJ, Wang RJ, et al. Discordance and clinical significance of ER, PR, and HER2 status between primary breast cancer and synchronous axillary lymph node metastasis. Med Oncol 2014;31:798. doi: 10.1007/s12032-013-0798-y
• 8. Bloom HJ, Richardson WW. Histological grading and prognosis in breast cancer; a study of 1409 cases of which 359 have been followed for 15 years. Br J Cancer 1957;11:359-77.
• 9. Ostrowski JL, Sawan A, Henry L, et al. p53 expression in human breast cancer related to survival and prognostic factors: an immunohistochemical study. J Pathol 1991;164:75-81.
• 10. Mahler-Araujo B, Savage K, Parry S, Reis-Filho JS. Reduction of E-cadherin expression is associated with non-lobular breast carcinomas of basal-like and triple negative phenotype. J Clin Pathol 2008;61:615-20. doi:10.1136/jcp.2007.053991.
• 11. Frickea E, Hermannstadtera C, Kellera G, et al. Effect of wild-type and mutant E-cadherin on cell proliferation and responsiveness to the chemotherapeutic agents Cisplatin, Etoposide, and 5-Fluorouracil. Oncology 2004;66:150-9. doi: 10.1159/000077442
• 12. Bukholm IK, Nesland JM, Burresen-Dale AL. Reexpression of E-cadherin, a catenin and b-catenin, but not of c-catenin, in metastatic tissue from breast cancer patients. J Pathol 2000;1:190:15-9. doi: 10.1002/(SICI)1096- 9896(200001)190:1<15:AID-PATH489>3.0.CO;2-L.
• 13. Gupta A, Deshpande CG, Badve S. Role of E-Cadherins in development of lymphatic tumor emboli. Cancer 2003;9:2341- 7. doi: 10.1002/cncr.11332.
• 14. Kim YT, Choi EK, Kim JW, Km OK, Kim SH Yang WI. Expression of E-cadherin and o-,I3-,y-catenin proteins in endometrial carcinoma. Yonsei Med J 2002;43:701-13. doi. org/10.3349/ymj.2002.43.6.701.
• 15. Nedergaard L, Haerslev T, Jacobsen GK. Immunohistochemical study of estrogen receptors in primary breast carcinomas and their lymph node metastases including comparison of two monoclonal antibodies. APMIS 1995;103:20-4. doi:10.1111/j.1699-0463.1995.tb01074.x
• 16. Raica M, Cîmpean AM, Ceausu RA, et al. Hormone receptors and HER2 expression in primary breast carcinoma and corresponding lymph node metastasis: do we need both? Anticancer Res 2014;34:1435-40. doi:10.1007/s12032-013- 0798-y
• 17. Yang LF, Song ST, Li XB, et al. Expression of c-erbB2 protein and its relation to prognosis in 284 primary breast cancer patients. Zhonghua Zhong Liu Za Zhi 2006;28:294-7.
• 18. Cobanoglu U, Ersoz S, Turgutalp H, Reis A, Ozoran Y. Correlation of Ecadherin expression with clinicopathological parameters in breast carcinoma. Saudi Med J 2004;25:1024-7.
• 19. Rakha EA, Abd EI Rehim D, Pinder SE, Lewis SA, Ellis IO. E-cadherin expression in invasive non-lobular carcinoma of the breast and its prognostic significance. Histopathology 2005;46:685-93. doi:10.1111/j.1365-2559.2005.02156.x.
• 20. Jeschke U, Mylonas I, Kuhn C, et al. Expression of E-cadherin in human ductal breast cancer carcinoma in situ, invasive carcinoma, their lymph node metastasis, their distant metastasis, carcinomas with recurrence and in recurrence. Anticancer Res 2007;27:1969-74.
• 21. Jones Jl, Royall JE, Walker RA. E-cadherin relates to EGFR expression and lymph node metastasis in primary breast carcinoma. Br J Cancer 1996;74:1287-41. doi:10.1038/ bjc.1996.522.
• 22. Hunt NCA, Douglas-Jones AG,Jasani B, Morgan JM, Pignatelli M. Loss of E-cadherin expression associated with lymph node metastases in small breast carcinomas. Virchows Archiv 1997;430:285-9.
• 23. Harigopal M, Berger AJ, Camp Rl, Rimm Dl, Kluger HM. Automated quantitative analysis of E-cadherin expression in lymph node metastases is predictive of survival in invasive ductal breast cancer. Clin Cancer Res 2005; 11:4083-9.
• 24. Howard EM, lau SK, lyles RH, et al. Correlation and expression of p53, HER-2, vascular endothelial growth factor (VEGF), and e-cadherin in a high-risk breast-cancer population. Int J Clin Oncol 2004;9:154-60. doi:10.1007/s10147-004-0386-4.
• 25. Charpin C, Garcia S, Bouvier C, et al. E-cadherin quantitative immunocytochemical assays in breast carcinomas. J Pathol 1997;181:294-300. doi:10.1002/(SICI)1096- 9896(199703)181:3<294:AID-PATH772>3.0.CO;2-V.
• 26. Parker C, Rampaul RS, Pinder SE, et al. E-cadherin as a prognostic indicator in primary breast cancer. Br J Cancer 2001;85:1958-63. doi: 10.1054/ bjoc.2001.2178.
• 27. Hosaka N, Ryu T, Cui W, et al. Relationship of p53, BcI-2, Ki-67 index and E-cadherin expression in early invasive breast cancers with comedonecrosis as an accelerated apoptosis. J Clin Pathol 2006;59:692-8. doi:10.1136/jcp.2005.030296.