Volume 11, Issue 4 (Vol.11 No.4 Jan 2023)                   rbmb.net 2023, 11(4): 532-546 | Back to browse issues page


XML Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Hagag S, Kodous A, Shaaban H A. Molecular and Immunohistochemical Alterations in Breast Cancer Patients in Upper Egypt. rbmb.net 2023; 11 (4) :532-546
URL: http://rbmb.net/article-1-1053-en.html
Radiation Biology department, National Center for Radiation Research & Technology, Egyptian Atomic Energy Authority, Nasr City, 8029, Cairo, Egypt.
Abstract:   (1953 Views)
Background: Breast cancer (BC) plays a major public health in Egyptian woman. In Upper Egypt, there is an increase in incidence of BC compared to other Egyptian areas. Triple-negative BC, estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-neu-negative, is a high-risk BC that lacks the benefit of specific therapy that targets these proteins. Accurate determination of Caveolin-1(Cav-1), Caveolin-2 (Cav-2) and HER-2/neu status have become of major clinical significance in BC by focusing about its role as a tumor marker for response to different therapies.

Methods: The present study was performed on 73 female BC patients in the South Egypt Cancer Institute. Blood samples were used for Cav-1, Cav-2, and HER-2/neu genes amplification and expression. In addition, immunohistological analysis of mammaglobin, GATA3, ER, PR, and HER-2/neu was done.

Results: There was a statistically significant association between Cav-1, 2 and HER-2/neu genes expression and the age of patients (P< 0.001). There are increase in the level of Cav-1, 2 and increase in HER-2/neu mRNA expression in groups treated with chemotherapy and group treated with both chemotherapy and radiotherapy compared to each group baseline level of genes mRNA expression before treatment. On the contrary, the group treated with chemotherapy, radiotherapy and hormonal therapy revealed increase on the level of Cav-1, 2 and HER-2/neu mRNA expression when compared with their baseline for the same patients before treatment.

Conclusions: Noninvasive molecular biomarkers such as Cav-1 and Cav-2 have been proposed for use in the diagnosis and prognosis for women with BC.
Full-Text [PDF 525 kb]   (1249 Downloads)    
Type of Article: Original Article | Subject: Molecular Biology
Received: 2022/09/22 | Accepted: 2022/10/30 | Published: 2023/04/3

References
1. Sabitha K, Kodous A, Rajkumar T. Computational analysis of mutations in really interesting new gene finger domain and BRCA1 c terminus domain of breast cancer susceptibility gene. Asian J Pharm Clin Res. 2016;9(3):96-102.
2. Shaban NZ, Ibrahim NK, Saada HN, El-Rashidy FH, Shaaban HM, Farrag MA, et al. miR-34a and miR-21 as biomarkers in evaluating the response of chemo-radiotherapy in Egyptian breast cancer patients. J Radiat Res Appl Sci. 2022;15(3):285-92. [DOI:10.1016/j.jrras.2022.08.001]
3. Omran MH, Fotouh BE, Shosha WG, Ismail A, Ramadan SS. Gene-Gene Interaction Study Between Genetic Polymorphisms of Folate Metabolism and MTR SNPs on Prognostic Features Impact for Breast Cancer. Rep Biochem Mol Biol. 2022;11(1):89-101. [DOI:10.52547/rbmb.11.1.89] [PMID] [PMCID]
4. Aglan SA, Zaki AM, EL Sedfy AS, El-Sheredy HG, Elgaddar OH. O6-Methylguanine-DNA Methyltransferase and ATP-Binding Cassette Membrane Transporter G2 Promotor Methylation: Can Predict the Response to Chemotherapy in Advanced Breast Cancer? Rep Biochem Mol Biol. 2022;11(1):20-9. [DOI:10.52547/rbmb.11.1.20] [PMID] [PMCID]
5. Verret B, Bottosso M, Hervais S, Pistilli B. The Molecular Predictive and Prognostic Biomarkers in Metastatic Breast Cancer: The Contribution of Molecular Profiling. Cancers (Basel). 2022;14(17):4203. [DOI:10.3390/cancers14174203] [PMID] [PMCID]
6. de Almeida CJG. Caveolin-1 and Caveolin-2 Can Be Antagonistic Partners in Inflammation and Beyond. Front Immunol. 2017;8:1530. [DOI:10.3389/fimmu.2017.01530] [PMID] [PMCID]
7. Qian XL, Pan YH, Huang QY, Shi YB, Huang QY, Hu ZZ, Xiong LX. Caveolin-1: a multifaceted driver of breast cancer progression and its application in clinical treatment. Onco Targets Ther. 2019;12:1539-1552. [DOI:10.2147/OTT.S191317] [PMID] [PMCID]
8. Simón L, Campos A, Leyton L, Quest AFG. Caveolin-1 function at the plasma membrane and in intracellular compartments in cancer. Cancer Metastasis Rev. 2020;39(2):435-53. [DOI:10.1007/s10555-020-09890-x] [PMID] [PMCID]
9. Cassandri M, Smirnov A, Novelli F, Pitolli C, Agostini M, Malewicz M, et al. Zinc-finger proteins in health and disease. Cell Death Discov. 2017;3: 17071. [DOI:10.1038/cddiscovery.2017.71] [PMID] [PMCID]
10. Querzoli P, Pedriali M, Rinaldi R, Secchiero P, Rossi PG, Kuhn E. GATA3 as an Adjunct Prognostic Factor in Breast Cancer Patients with Less Aggressive Disease: A Study with a Review of the Literature. Diagnostics (Basel). 2021;11(4):604. [DOI:10.3390/diagnostics11040604] [PMID] [PMCID]
11. Miettinen M, McCue PA, Sarlomo-Rikala M, Rys J, Czapiewski P, Wazny K, et al. GATA3: a multispecific but potentially useful marker in surgical pathology: a systematic analysis of 2500 epithelial and nonepithelial tumors. Am J Surg Pathol. 2014;38(1):13-22. [DOI:10.1097/PAS.0b013e3182a0218f] [PMID] [PMCID]
12. Catto JWF, Rosario DJ. The road to cystectomy: Who, when and why? EAU Updat Ser. 2005;3:118-28. [DOI:10.1016/j.euus.2005.07.001]
13. Elston CW, Ellis IO, Pinder SE. Pathological prognostic factors in breast cancer. Crit Rev Oncol. 1999;31(3):209-23. [DOI:10.1016/S1040-8428(99)00034-7] [PMID]
14. Vajpeyi R. WHO classification of tumours: pathology and genetics of tumours of the breast and female genital organs. World Heal Organ. 2005, 58(6):671-72.
15. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402-8. [DOI:10.1006/meth.2001.1262] [PMID]
16. Arafah M. Correlation of hormone receptors with Her-2 Neu protein expression and the histological grade in invasive breast cancers in a cohort of Saudi Arabia. Turk Patoloji Derg. 2012;28(1):38-43. [DOI:10.5146/tjpath.2012.01095] [PMID]
17. Fabi A, Di Benedetto A, Metro G, Perracchio L, Nisticò C, Di Filippo F, at al. HER2 protein and gene variation between primary and metastatic breast cancer: significance and impact on patient care. Clin Cancer Res. 2011;17(7):2055-64. [DOI:10.1158/1078-0432.CCR-10-1920] [PMID]
18. Rydén L, Landberg G, Stål O, Nordenskjöld B, Fernö M, Bendahl PO. HER2 status in hormone receptor positive premenopausal primary breast cancer adds prognostic, but not tamoxifen treatment predictive, information. Breast Cancer Res Treat. 2008;109(2):351-7. [DOI:10.1007/s10549-007-9660-2] [PMID]
19. Ansquer Y, Mandelbrot L, Lehy T, Salomon L, Dhainaut C, Madelenat P, et al. Expression of BRCA1, HER-1 (EGFR) and HER-2 in sporadic breast cancer and relationships to other clinicopathological prognostic features. Anticancer Res. 2005;25(6C):4535-41.
20. Margalit DN, Sreedhara M, Chen YH, Catalano PJ, Nguyen PL, Golshan M, et al. Microinvasive breast cancer: ER, PR, and HER-2/neu status and clinical outcomes after breast-conserving therapy or mastectomy. Ann Surg Oncol. 2013;20(3):811-8. [DOI:10.1245/s10434-012-2640-8] [PMID]
21. Bánkfalvi A, Simon R, Brandt B, Bürger H, Vollmer I, Dockhorn-Dworniczak B, et al. Comparative methodological analysis of erbB-2/HER-2 gene dosage, chromosomal copy number and protein overexpression in breast carcinoma tissues for diagnostic use. Histopathology. 2000;37(5):411-9. [DOI:10.1046/j.1365-2559.2000.00984.x] [PMID]
22. Alunni-Fabbroni M, Sandri MT. Circulating tumour cells in clinical practice: Methods of detection and possible characterization. Methods.2010;50(4):289-97. [DOI:10.1016/j.ymeth.2010.01.027] [PMID]
23. El Hag MI, Hag AM, Ha JP, Michael CW. Comparison of GATA-3, mammaglobin, GCDFP-15 expression in breast carcinoma in serous effusions: A cell-block micro-array study. Pleura Peritoneum. 2017;2(3):143-8. [DOI:10.1515/pp-2017-0014] [PMID] [PMCID]
24. Asselin-Labat ML, Sutherland KD, Barker H, Thomas R, Shackleton M, Forrest NC, et al. Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation. Nat Cell Biol. 2007;9(2):201-9. [DOI:10.1038/ncb1530] [PMID]
25. Shield PW, Papadimos DJ, Walsh MD. GATA3: a promising marker for metastatic breast carcinoma in serous effusion specimens. Cancer Cytopathol. 2014;122(4):307-12. [DOI:10.1002/cncy.21393] [PMID]
26. Braxton DR, Cohen C, Siddiqui MT. Utility of GATA3 immunohistochemistry for diagnosis of metastatic breast carcinoma in cytology specimens. Diagn Cytopathol. 2015;43(4):271-7. [DOI:10.1002/dc.23206] [PMID]
27. Huo L, Gong Y, Guo M, Gilcrease MZ, Wu Y, Zhang H, et al. GATA‐binding protein 3 enhances the utility of gross cystic disease fluid protein‐15 and mammaglobin A in triple‐negative breast cancer by immunohistochemistry. Histopathology. 2015;67(2):245-54. [DOI:10.1111/his.12645] [PMID]
28. Sangoi AR, Shrestha B, Yang G, Mego O, Beck AH. The Novel Marker GATA3 is Significantly More Sensitive Than Traditional Markers Mammaglobin and GCDFP15 for Identifying Breast Cancer in Surgical and Cytology Specimens of Metastatic and Matched Primary Tumors. Appl Immunohistochem Mol Morphol. 2016;24(4):229-37. [DOI:10.1097/PAI.0000000000000186] [PMID] [PMCID]
29. Lee J, Min W, Kim S, Son B. Comparison of serum HER-2/neu between trastuzumab-based regimen and anthyracycline-based regimen during neoadjuvant chemotherapy in advanced primary breast cancer. J Clin Oncol. 2009;27(15 suppl):e11582. [DOI:10.1200/jco.2009.27.15_suppl.e11582]
30. McArdle CS, McMillan DC, Greenlaw N, Morrison DS. Adjuvant radiotherapy and chemotherapy in breast cancer: 30 year follow-up of survival. BMC Cancer. 2010;10:398. [DOI:10.1186/1471-2407-10-398] [PMID] [PMCID]
31. Zhang W, Becciolini A, Biggeri A, Pacini P, Muirhead CR. Second malignancies in breast cancer patients following radiotherapy: a study in Florence, Italy. Breast Cancer Res. 2011;13(2):R38. [DOI:10.1186/bcr2860] [PMID] [PMCID]
32. Fard ZT, Nafisi N. The Relationship Between 6 Polymorphisms of Caveolin-1 Gene and the Risk of Breast Cancer. Clin Breast Cancer. 2018;18(5): e893-e898. [DOI:10.1016/j.clbc.2018.01.005] [PMID]
33. Pucci M, Bravatà V, Forte GI, Cammarata FP, Messa C, Gilardi MC, Minafra L. Caveolin-1, breast cancer and ionizing radiation. Cancer Genomics Proteomics. 2015;12(3):143-52.
34. Yeong J, Thike AA, Ikeda M, Lim JCT, Lee B, Nakamura S, et al. Caveolin-1 expression as a prognostic marker in triple negative breast cancers of Asian women. J Clin Pathol. 2018;71(2):161-7. [DOI:10.1136/jclinpath-2017-204495] [PMID]
35. Kang J, Park JH, Lee HJ, Jo U, Park JK, Seo JH, et al. Caveolin-1 Modulates Docetaxel-Induced Cell Death in Breast Cancer Cell Subtypes through Different Mechanisms. Cancer Res Treat. 2016;48(2):715-26. [DOI:10.4143/crt.2015.227] [PMID] [PMCID]
36. Badana AK, Chintala M, Gavara MM, Naik S, Kumari S, Kappala VR, et al. Lipid rafts disruption induces apoptosis by attenuating expression of LRP6 and survivin in triple negative breast cancer. Biomed Pharmacother. 2018;97:359-368. [DOI:10.1016/j.biopha.2017.10.045] [PMID]
37. Du C, Chen L, Zhang H, Wang Z, Liu W, Xie X, Xie M. Caveolin-1 limits the contribution of BKCa channel to MCF-7 breast cancer cell proliferation and invasion. Int J Mol Sci. 2014;15(11):20706-22. [DOI:10.3390/ijms151120706] [PMID] [PMCID]
38. S Shi XY, Xiong LX, Xiao L, Meng C, Qi GY, Li WL. Downregulation of caveolin 1 upregulates the expression of growth factors and regulators in co culture of fibroblasts with cancer cells. Mol Med Rep. 2016;13(1):744-52. 39. Wang R, He W, Li Z, Chang W, Xin Y, Huang T. Caveolin-1 functions as a key regulator of 17β-estradiol-mediated autophagy and apoptosis in BT474 breast cancer cells. Int J Mol Med. 2014;34(3):822-7. [DOI:10.3892/ijmm.2014.1836] [PMID]
39. Shi Y, Tan SH, Ng S, Zhou J, Yang ND, Koo GB, et al. Critical role of CAV1/caveolin-1 in cell stress responses in human breast cancer cells via modulation of lysosomal function and autophagy. Autophagy. 2015;11(5):769-84. [DOI:10.1080/15548627.2015.1034411] [PMID] [PMCID]
40. Witkiewicz AK, Kline J, Queenan M, Brody JR, Tsirigos A, Bilal E, et al. Molecular profiling of a lethal tumor microenvironment, as defined by stromal caveolin-1 status in breast cancers. Cell Cycle. 2011;10(11):1794-809. [DOI:10.4161/cc.10.11.15675] [PMID] [PMCID]
41. Mallini P, Lennard T, Kirby J, Meeson A. Epithelial-to-mesenchymal transition: what is the impact on breast cancer stem cells and drug resistance. Cancer Treat Rev. 2014;40(3):341-8. [DOI:10.1016/j.ctrv.2013.09.008] [PMID]
42. Ariana M, Arabi N, Pornour M, Vaseghi H, Ganji SM, Alivand MR, et al. The diversity in the expression profile of caveolin II transcripts, considering its new transcript in breast cancer. J Cell Biochem. 2018;119(2):2168-2178. [DOI:10.1002/jcb.26378] [PMID]
43. Chung YC, Kuo JF, Wei WC, Chang KJ, Chao WT. Caveolin-1 Dependent Endocytosis Enhances the Chemosensitivity of HER-2 Positive Breast Cancer Cells to Trastuzumab Emtansine (T-DM1). PLoS One. 2015;10(7) :e0133072. [DOI:10.1371/journal.pone.0133072] [PMID] [PMCID]
44. Lee SR. Critical Role of Zinc as Either an Antioxidant or a Prooxidant in Cellular Systems. Oxid Med Cell Longev. 2018; 20;2018:9156285. [DOI:10.1155/2018/9156285] [PMID] [PMCID]

Add your comments about this article : Your username or Email:
CAPTCHA

Send email to the article author


Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2015 All Rights Reserved | Reports of Biochemistry and Molecular Biology

Designed & Developed by : Yektaweb