Correlation between Serum and Tissue Markers in Breast Cancer Iraqi Patients

Main Article Content

Abeer M. Hussain
Alia Hussein Ali
Haider Latif Mohammed

Abstract

Breast cancer is the most prevalent malignancy among women worldwide, in Iraq it ranks the first among the population and the leading cause of cancer related female mortality. This study is designed to investigate the correlations between serum and tissue markers in order to clarify their role in progression or regression breast cancer. Tumor Markers are groups of substances, mainly proteins, produced from cancer cell or from other cells in the body in response to tumor.  The study was carried out from April 2018 to April 2019 with total number of 60 breast cancer women. The blood samples were collected from breast cancer women in postoperative and pretherapeutic who attended teaching oncology hospital of the medical city in Baghdad and the serum markers evaluated by ELISA technique are Carbohydrate Antigen 15-3 (Ca 15-3), Carbohydrate Antigen 27.29 (Ca 27.29), Anti-Mullerian Hormone (AMH), Tumor Necrosis Factor-Alpha (TNF-α), Interleukin-6 (IL-6), Interleukin-10 (IL-10) and Human Epidiymis Protein-4 (HE4). Tissue samples were collected for the same breast cancer women who attended medical city, Baghdad with total number 30. The tissue markers evaluated by Immunohistochemical technique are Estrogen Receptor (ER), Progesterone Receptor (PR), Human Epidermal Growth Factor Receptor 2 (Her 2/neu) and Cyclin E. The results showed a positive significant correlation (p = 0.017) between Ca 27.29 and Her-2/neu, (p = 0.038) between IL-6 and cyclin E phenotype, (p = 0.051) between TNF-α and Cyclin E intensity, (p = 0.005) between HE4 and Her-2/neu, and negative significant correlation (p = 0.058) between IL-10 and ER score and (p = 0.045) between HE4 with Cyclin E intensity. We conclude from these correlations that positive correlations increasing disease progression, like correlation between Ca 27.29 and Her-2/neu, cyclin E with IL-6 and cyclin E with TNF-α. And the negative correlations may contribute to delay disease, like correlation between IL-10 and ER. From the correlations results in this study, it is clear that the Ca 27.29, Her-2 / neu, cyclin E markers play an important role in disease progression.

Article Details

How to Cite
1.
Correlation between Serum and Tissue Markers in Breast Cancer Iraqi Patients. Baghdad Sci.J [Internet]. 2022 Jun. 1 [cited 2024 Nov. 19];19(3):0501. Available from: https://bsj.uobaghdad.edu.iq/index.php/BSJ/article/view/4565
Section
article

How to Cite

1.
Correlation between Serum and Tissue Markers in Breast Cancer Iraqi Patients. Baghdad Sci.J [Internet]. 2022 Jun. 1 [cited 2024 Nov. 19];19(3):0501. Available from: https://bsj.uobaghdad.edu.iq/index.php/BSJ/article/view/4565

References

AICR: American Institute of Cancer Research. Diet, Nutrition, Physical activity and breast cancer.World Cancer Research Fund. 2017 .Pp: 4.

Martínez-Montiel N, Anaya-Ruiz M, Pérez-Santos M, Martínez-Contreras RD. Alternative Splicing in Breast Cancer and the Potential Development of Therapeutic Tools. Genes. 2017 Oct; 8 (217): 1 – 14. Available from www.mdpi.com/journal/genes DOI: 10.3390/genes8100217.

Alwan NAS, Shawkat MM. Treatment Options and Follow-Up among Iraqi Patients with Breast Carcinoma. European J of Med and Health Sci. 2020 March; 2 (2): 1 – 6. DOI: http://dx.doi.org/10.24018/ejmed.2020.2.2.171.

Annual Report, Iraqi Cancer Registry (ICR). 2016. Republic of Iraq, Ministry of Health/Environment Iraqi Cancer Board.

Velpula N, Yathavakilla ChN, Ramesh A. Tumor Markers- A Review. Int J of Oral Health Dentistry. 2017 Jan-Mar; 3 (1): 1 – 5. DOI: 10.18231/2395-499X.2017.0001.

Abed SN, Mahdi HS, Sahib AS, Abo Almaali MHM, AL-Haydar M, Mohsin KK. Serum Levels of Cancer Antigen 15.3 and Estrogen in a Samples of Iraqi Women with Breast Cancer Treated with Anastrazole. Int J of Pharmaceut Res. 2020 Jan [2020 Jun]; 1: 1604- 1608. DOI: https://doi.org/10.31838/ijpr/2020.SP1.246.

Kabel AM. Tumor markers of breast cancer: New prospective. J of Oncol Sci. 2017 Jan [2017 Jan 16]; 3 (1): 5 – 11 . Available from http://dx.doi.org DOI: 10.1016/j.jons.2017.01.001.

Loeser A. The insiders guide to Metastatic Breast cancer. A Summary of the disease and its treatments. 2017 .Pp: 7, 8.

Lehmann P, Vélez MP, Saumet J, Lapensée L, Jamal W, Bissonnette F, et al . Anti-Müllerian hormone (AMH): a reliable biomarker of oocyte quality in IVF. J Assist Reprod Genet. 2014 Feb [2014 Feb 27]; 31 (1): 493 – 498. DOI: 10.1007/s10815-014-0193-4.

Helena M. Anti-Müllerian hormone as a marker of ovarian reserve in girls before, during and after treatment for childhood cancer. MSc. Thesis. Lund University; 2017.

Saadullah SM, Sulaiman DM. Anti-Mullerian Hormone Level in Patients with Polycystic Ovary Syndrome. Med J of Babylon. 2018 Oct-Dec [2018]; 15(4): 295 – 299. Available from www.medjbabylon.org . DOI: 10.4103/MJBL.MJBL-98-18.

Eliassen AH, Zeleniuch-Jacquotte A, Rosner B, Hankinson SE. Plasma anti-Müllerian hormone concentrations and risk of breast cancer among premenopausal women in the Nurses’ Health Studies. Cancer Epidemiol Biomarkers Prev. 2016 May [2017 May 1; 25 (5): 854 – 860. DOI: 10.1158/1055-9965.EPI-15-1240.

Kadhum NH. Determination Anti-Mullerian Hormone and Vitamin D in Breast Cancer patients. World J of Pharmaceut Res. 2017 Aug; 6 (9): 48 – 59. DOI: 10.20959/wjpr20179-9232.

Al-Dulaimy NH, Hassan AJ, Al-Araji SM. Estimation of Interferon-α (IFN-α) and Tumor Necrosis Factor-α (TNF-α) in Female Rats Immunized by Human Breast Cancer Cell Line T47D. J of Babylon University/Pure and Applied Sci. 2016; 9 (24): 2449 – 2455.

Katanov Ch, Lerrer Sh, Liubomirski Y, Leider-Trejo L, Meshel T, Bar J, et al . Regulation of the inflammatory profile of stromal cells in human breast cancer: prominent roles for TNF-α and the NF-κB pathway. Stem Cell Res and Therapy. 2015 Apr [2015 May 1]; 6 (87): 1 – 17. DOI: 10.1186/s13287-015-0080-7.

Ma Y, Ren Y, Zhi-Jun D, Cai-Jun W, Yan-Hong J, Xu J. IL-6, IL-8 and TNF-α levels correlate with disease stage in breast cancer patients. Adv Clin Exp Med. 2017; 26 (3): 421 – 426. DOI: 10.17219/acem/62120.

Mercogliano MF, Bruni S, Elizalde PV, Schillaci R. Tumor Necrosis Factor α Blockade: An Opportunity to Tackle Breast Cancer. Front Oncol . 2020 Mar [2020 Apr 22]; 10: 1 – 25. Available from www.frontiersin.org DOI: 10.3389/fonc.2020.00584.

Zappavigna S, Cossu AM, Grimaldi A, Bocchetti M, Ferraro GA, Nicoletti GF, et al. Anti-Inflammatory Drugs as Anticancer Agents. Int J of Mol Sci. 2020 Apr [2020 Apr 9]; 21: 1 – 29. Available from www.mdpi.com/journal/ijms DOI: 10.3390/ijms21072605.

Ahmad N, Ammar A, Storr SJ, Green AR, Rakha E, Ellis IO, et al . IL-6 and IL-10 are associated with good prognosis in early stage invasive breast cancer patients. Cancer Immunol, Immunotherapy. 2017 Dec [2017 Dec 18]; 67: 537 – 549. Available from http:// doi.org DOI: 10.1007/s00262-017-2106-8.

Al.Thwani AN, Mohsin SM. Serum level of Interleukin-6 in Breast Cancer Iraqi Women. Iraqi J of Cancer and Med Genetics. 2012; 5 (1): 42 – 45.

Sheikhpour E, Noorbakhsh P, Foroughi E, Farahnak S, Nasiri R, Neamatzadeh H. A Survey on the Role of Interleukin-10 in Breast Cancer: A Narrative. Rep Biochem Mol Biol. 2018 Jul; 7 (1): 30 – 37.

Al-Ankoshy AAM, Alatbee AHD. The impact of IL-10 gene polymorphism on progressive Breast cancer. J Pharm Sci and Res. 2019; 11(1): 93-97.

Sirsikar M, Pinnelli VBK, Raghavendra DS. Diagnostic and Prognostic Performance of Human Epididymis Secretary Protein- 4 (HE4) in Cancer Treatment: A Review. World J of Pharmaceut Res. 2016 Dec; 5 (1): 406 – 420.

Celik B, Bulut T. Human epididymis protein 4 may not be a reliable screening biomarker for detecting lung carcinoma patients. Biomed Rep. 2017 Aug; 7 (1): 297 – 300. DOI: 10.3892/br.2017.971.

Kemal Y, Demirag G, Bedir AB-K, Tomak L, Derebey M, Erdem D, et al . Serum human epididymis protein 4 levels in colorectal cancer patients. Mol and Clin Oncol. 2017 Jul; 7 (1): 481 - 485. DOI: 10.3892/mco.2017.1332.

Gunduz UR, Gunaldi M, Isiksacan N, Gunduz S, Okuturlar Y, Kocoglu H. A new marker for breast cancer diagnosis, human epididymis protein 4: A preliminary study. Mol and Clin Oncol. 2016 May; 5: 355 – 360. DOI: 10.3892/mco.2016.919.

AL-Bedairy IH, AL-Faisal AHM, AL-Gazali HR, AL-Mudhafar H. Molecular Subtypes by Immunohistochemical for Iraqi Women with Breast Cancer. Iraqi J of Biotechnol. 2020 Apr [2020 Apr 30]; 19 (1): 19-28.

Chasib ThJ, Al-Hawaz M, Jasim NH. Evaluation of The Estrogen and Progesterone Receptors in Female Breast cancer in Respect to Age, Grade and Stage. Bas J Surg. 2013 Sep; 9 – 14.

Wang J, Xu B. Targeted therapeutic options and future perspectives for HER2-positive breast cancer. Signal transduct. target. ther. 2019 Sep [2019 Aug 22] ; 4 ( 34 ) : 1 – 22. Available from http://doi. Org DOI: 10.1038/s41392-019-0069-2.

Sareyeldin RM, Gupta I, Al-Hashimi I, Al-Thawadi HA, Al Farsi HF, Vranic S, et al . Gene Expression and miRNAs profiling: Function and Regulation in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer. Cancers. 2019 May; 11 (646): 1 – 20. DOI: 10.3390/cancers 11050646.

Furrer D, Paquet C, Jacob S, Diorio C. The Human Epidermal Growth Factor Receptor 2 (HER2) as a prognostic and predictive biomarker: molecular insights into HER2 activation and diagnostic implications. IntechOpen. 2018; 11 – 3. Available from http: // dx.doi.org DOI: 10.5772/intechopen.78271.

Chappuis PO, Donato E, Goffin JR, Wong N, Be´gin LR, Kapusta LR, et al . Cyclin E expression in breast cancer: predicting germline BRCA1 mutations, prognosis and response to treatment. Ann Oncol. 2004 Dec [2005 Mar 31]; 16: 735 – 742. DOI: 10.1093/annonc/mdi149.

Hwang HC, Clurman IS. Cyclin E in normal and neoplastic cell cycles. Oncogene. 2005; 24: 2776 – 2786. DOI: 10.1038/sj.onc.1208613.

Ryu M, Sung ChK, Im YJ, Chun Ch. Activation of JNK and p38 in MCF-7 cells and the In Vitro Anticancer Activity of Alnus hirsute Extract. Molecules. 2020 Feb [2020 Feb 27]; 25(1073): 1-23. Available from www.mdpi.com/journal/molecules DOI: 10.3390/molecules25051073.

Kabiraj A, Gupta J, Khaitan T, Bhattacharya PT. Principle And Techniques of Immunohistochemistry-A Review. Int J Biol Med Res. 2015; 6(3): 5204-5210. Available from www.biomedscidirect.com.

Iqbal BM, Buch A. Hormone receptor (ER, PR, and HER2/neu) status and proliferation index marker (Ki-67) in breast cancers: Their onco-pathological correlation, shortcomings and future trends. Medical J of Dr. D.Y. Patil Univ. 2016 [2016]; 9 (6): 674 – 679. DOI: 10.4103/0975-2870.194180.

Karakas C, Biernacka A, Bui T, Sahin AA, Yi M, Akli S, et al. Cytoplasmic Cyclin E and Phospho-Cyclin - Dependent Kinase 2 Are Biomarkers of Aggressive Breast Cancer. The Am J of Pathol. 2016 Feb; 186 (7): 1900 – 1912. Available from http:// dx.doi.org DOI: 10.1016/j.ajpath.2016.02.024.

Zhuangwei LV, Liu M, Shen J, Xiang D, Yunfeng MA, Yanhong JI. Association of serum interleukin 10, interleukin 17A and transforming growth factor-α levels with human benign and malignant breast diseases. Exper and Ther Med. 2018 Jan; 15: 5475 – 5480. DOI: 10.3892/etm.2018.6109.

Bhattacharjee HK, Bansal VK, Nepal B, Srivastava S, Dinda AK, Misra MC. Is Interleukin 10 (IL10) Expression in Breast Cancer a Marker of Poor Prognosis? Indian J Surg Oncol. 2016 Feb [2016 Feb 20]; 7 (3): 320 – 325. DOI: 10.1007/s13193-016-0512-6.

Qiao Y, He H, Jonsson Ph, Sinha I, Zhao Ch, Dahlman -Wright K. AP-1 Is a Key Regulator of Proinflammatory Cytokine TNF- α mediated Triple-negative Breast Cancer Progression . The J of biol chem. 2016 Jan; 291 (10): 5068 – 5079. DOI: 10.1074/jbc.M115.702571.

Carruba G, D’Agostino P, Miele M, Calabro M, Barbera C, Di Bella G, et al . Estrogen Regulates Cytokine Production and Apoptosis in PMA-Differentiated, Macrophage-Like U937 Cells. J of Cell Biochem. 2003 May; 90: 187 – 196. DOI: 10.1002/jcb.10607.

Yerushalmiv R, Tyldesley S, Kennecke H, Speers C, Woods R, Knight B, et al . Tumor markers in metastatic breast cancer subtypes: frequency of elevation and correlation with outcome. Ann of Oncol. 2011 May; 23 (2): 338 – 345. DOI: 10.1093/annonc/mdr154.

Klee GG, Schreiber WE. MUC1 Gene–Derived Glycoprotein Assays for Monitoring Breast Cancer (CA 15-3, CA 27.29, and BR) Are They Measuring the Same Antigen? Arch Pathol Lab Med. 2004 Jun; 128: 1131 – 1135.

Conley SJ, Bosco EE, Tice DA, Hollingsworth RE, Herbst R, Xiao Z. HER2 drives Mucin-like 1 to control proliferation in breast cancer cells. Oncogene. 2015 Nov [2016 Jan 4]; 35: 4225 – 4234. DOI: 10.1038/onc.2015.487.

Raina D, Uchida Y, Kharbanda A, Rajabi H, Panchamoorthy G, Jin C, et al . Targeting the MUC1-C oncoprotein downregulates Her-2 activation and abrogates trastuzumab resistance in breast cancer cells. Oncogene. 2014 Jun [2014 Dec 26]; 33 (26): 3422 – 3431. DOI: 10.1038/onc.2013.308.

Akoz G, Diniz G, Ekmekci S, Ekin ZY, Uncel M. Evaluation of human epididymal secretory protein 4 expression according to the molecular subtypes (luminal A, luminal B, human epidermal growth factor receptor 2-positive, triple-negative) of breast cancer. Indian J Pathol Microbiol. 2018 [2018 Jul 30 ] ; 61 ( 3 ): 323 – 329 .

Zhu L, Zhuang H, Wang H, Tan M, Schwab CL, Deng L, et al. Overexpression of HE4 (human epididymis protein 4) enhances proliferation, invasion and metastasis of ovarian cancer. Oncotarget. 2015 Oct; 1 – 16.

Hsu JL, Hung M-Ch. The role of HER2, EGFR, and other receptor tyrosine kinases in breast cancer. Cancer Metastasis Rev. 2016 Dec [2017 Dec 1]; 35 (4): 575 – 588. DOI: 10.1007/s10555-016-9649-6.

Wei L-H, Baumann H, Tracy E, Wang Y, Hutson A, Rose-John S, et al . Interleukin-6 Trans signalling enhances photodynamic therapy by modulating cell cycling. Brit J of Cancer. 2007 Oct [2007 Nov 6 ]; 97 : 1513 – 1522. DOI: 10.1038/sj.bjc.6604073.

Pan Y, Claret FX. Jab1/Csn5 Signaling in Breast Cancer. Intech. 2017; 199 – 211. Available from http:// dx.doi.org DOI: 10.5772/66174.

Shackleford TJ, Claret FX. JAB1/CSN5: a new player in cell cycle control and cancer. Cell Division. 2010 [2010 ] ; 5 ( 26 ) : 1 – 14 . DOI: 10.1186/1747-1028-5-26.

Dhillon NK, Mudryj M. Cyclin E overexpression enhances cytokine-mediated apoptosis in MCF7 breast cancer cells. Genes Immun. 2002 Dec; 4: 336 – 342. DOI: 10.1038/sj.gene.6363973.

Lee AV, Oesterreich S, Davidson NE. MCF-7 Cells—Changing the Course of Breast Cancer Research and Care for 45 Years. JNCI J Natl Cancer Inst. 2015 Feb; 107 (7): 1 – 4. DOI: 10.1093/jnci/djv073.

Wang J, Deng L, Zhuang H, Liu J, Liu D, Li X, et al . Interaction of HE4 and ANXA2 exists in various malignant cells—HE4–ANXA2–MMP2 protein complex promotes cell migration. Cancer Cell Int. 2019 May [2019 Jun 13]; 19 (161): 1- 12. Available from http:// doi.org DOI: 10.1186/s12935-019-0864-4.

Gibbs LD, Chaudhary P, Mansheim K, Hare RJ, Mantsch RA, Vishwanatha JK. ANXA2 Expression in African American triple-negative breast cancer patients. Breast Cancer Res and Treat. 2018 Oct [2018 Nov 26]; 1 – 8. Available from http:// doi.org DOI: 10.1007/s10549-018-5030-5.

Wu M, Sun Y, Xu F, Liang Y, Liu H, Yi Y. Annexin A2 Silencing Inhibits Proliferation and Epithelial-to mesenchymal Transition through p53-Dependent Pathway in NSCLCs. J of Cancer. 2019 Jan; 10 (5): 1077 – 1085. DOI: 10.7150/jca.29440

Bashour SI, Doostan I, Keyomarsi K, Valero V, Ueno NT, Brown PH, et al. Rapid Breast Cancer Disease Progression Following Cyclin Dependent Kinase 4 and 6 Inhibitor Discontinuation. J of Cancer. 2017 Jul; 8 (1): 2004 – 2009. DOI: 10.7150/jca.18196.

Alawadi AF, Al-Nuaimi DS, Al-Naqqash MA, Alshewered AS. Time to Progression of Early Versus Advanced Breast Cancer in Iraq. La Prensa Medica Argentina. 2019 Dec [2020 Jan 2]; 106 (1): 1 – 5.

Al Zobair AA, Jasim BI, Al Obeidy BF, Jawher NMT. Prognostic impact of hormone and HER2 status on the prognosis of breast cancer in Mosul. Ann. Trop. Med. Public Health . 2020 Apr; 23(7): 844 – 854. Available from http://doi.org DOI: 10.36295/ASRO.2020.2375.

Goldvaser H, Korzets Y, Shepshelovich D, Yerushalmi R, Sarfaty M, Ribnikar D, et al. Deescalating Adjuvant Trastuzumab in HER2-Positive Early-Stage Breast Cancer: A Systemic Review and Meta-Analysis. JNCI Cancer Spectrum. 2019 Mar[2019 Apr 26]; 3(2): 1 – 8. Available from http://creativecommons.org/licenses/by-nc/4.0/ DOI: 10.1093/jncics/pkz033.

Hunt KK, Karakas C, Ha MJ, Biernacka A, Yi M, Sahin AA, et al. Cytoplasmic Cyclin E Predicts Recurrence in Patients with Breast Cancer. Clin Cancer Res. 2016 Nov[2017 Jun 15]; 23(12): 2991 – 3002. Available from www.aacrjournals.org DOI: 10.1158/1078-0432.CCR-16-2217.

Delk NA, Hunt KK, Keyomarsi K. Altered Subcellular Localization of Tumor-Specific Cyclin E Isoforms Affects Cyclin-Dependent Kinase 2 Complex Formation and Proteasomal Regulation. Cancer Res. 2009 Apr; 69(7): 2817 – 2825. Available from PMC DOI: 10.1158/0008-5472.CAN-08-4182.