Fatima Djilali DOULA, Latifa MOHAMMEDI, Farida MESLI, Rchid SENHADJI

Immunohistochemical evaluation of mitogenic activity in breast cancers by TFF1/PS2 protein and HER2 oncoprotein expression in western Algeria

Breast carcinoma is a disease with a tremendous heterogeneity in its clinical behavior. Newer prognostic factors and predictors of response to therapy are needed. The purpose of the current study was to investigate TFF1 expression in breast cancer, and its relation with tumor malignancy and proliferation measured by HER2 status. This is a prospective study conducted on 538 women with primary ductal/lobular invasive breast carcinomas in the department of pathology at the regional military university hospital of Oran (Algeria). The mitogenic activity was evaluated by a conventional immunohistochemical (IHC) approach, validated as a replacement technique for microarray analysis by labeling the antigens TFF1, HER2, ERα, and PgR. Correlations between the different parameters were carried out. TFF1 was correlated positively with hormonal receptors (HR) (P<0.0001) and negatively with HER2 (P<0.0001) and histological grade but with marginal significance (P<0.1). According to mitogenic activity, patients were individualized into two subgroups: low proliferation tumors (Luminal A) representing 51.3% of cases and high proliferation ones representing 48.7% of cases (Luminal B, Basal, HER2, Claudin-Low). Mitogenic activity majored by HER2 overexpression correlates with aggressiveness parameters such as high histological SBR grade, larger tumor size, young age at presentation, and negative TFF1/HR status. IHC methods are less expensive and more cost-effective for the establishment of molecular subclasses.

Keywords:

Breast cancer, HER2, mitogenic activity, TFF1,

PDF

___

Elston CW. and Ellis JO. 1991. Pathological prognostic factors in breast cancer. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 19: 403-410. https://dx.doi.org/ 10.1111/j.1365-2559.1991.tb00229.x
Vincent-salomon A, Rousseau A, Jouve M, Beuzeboc P, Sigal-Zafrani B, Fréneaux P, Rosty C, Nos C, Campana F, Klijanienko J, Al Ghuzlan A, Sastre-Garau X. 2004. Breast Cancer Study Group. Proliferation markers predictive of the pathological response and disease outcome of patients with breast carcinomas treated by anthracycline-based preoperative chemotherapy. Eur J Cancer. 40 (10):1502-1508. https://doi: 10.1016/j.ejca.2004.03.014. [Pub Med] [Cross Ref]
Bollet MA, Sigal-Zafrani B, Gambotti L, Extra JM, Meunier M, Nos C., Dendale R, Campana F, Kirova YM, Diéras V, Fourquet A. 2006. For The Institut Curie Breast Cancer Study Group. Pathological response to preoperative concurrent chemo-radiotherapy for breast cancer: Results of a phase II study. Eur J Cancer. 42(14):2286–2295. https:// doi:10.1016/j.ejca.2006.03.026. [Pub Med]
Macgrogan G, Mauriac L, Durand M, Bonichon F, Trojani M, de Mascarel I, Coindre JM. 1996. Primary chemotherapy in breast invasive carcinoma: predictive value of the immunohistochemical detection of hormonal receptors, p53, c-erbB-2, MiB1, pS2 and GST pi. Br J Cancer. 74 (9):1458-1465.
Guarneri V, Broglio K, Kau SW, Cristofanilli M, Buzdar AU, Valero V, Buchholz T, Meric F, Middleton L, Hortobagyi GN, Gonzalez-Angulo AM. 2006. Prognostic value of pathologic complete response after primary chemotherapy in relation to hormone receptor status and other factors. J Clin Oncol. 24 (7):103-144.
Kwok TC, Rakha EA, Lee AH, Grainge, M., Green, A.R., Ellis, I.O., Powe, D.G. 2010. Histological grading of breast cancer on needle core biopsy: the role of immunohistochemical assessment of proliferation. Histopathology; 57 (2): 212-219. https://dx.doi: 10.1111/j.1365-2559.2010.03620.x
Buache E, Etique N, Alpy F, Stoll I, Muckensturm M, Reina-San-Martin B, Chenard MP, Tomasetto C, Rio MC. 2011. Deficiency in trefoil factor 1 (TFF1) increases tumorigenicity of human breast cancer cells and mammary tumor development in TFF1-knockout mice. Oncogene. 30: 3261-3273. https://doi:10.1038/onc.2011.41
Ioakim-Liossi A, Karakitsos P, Markopoulos C, Aroni K, Delivelioti K, Gogas J, Kyrkou K. 1997. Expression of pS2 Protein and Estrogen and Progesterone Receptor Status in Breast Cancer. Acta Cytol. 41(3): 713-716. https://dx.doi: 10.1159/000332690 Source: PubMed
Almasri NM. and AL Hamad M. 2005. Immunohistochemical evaluation of human epidermal growth factor receptor 2 and estrogen and progesterone receptors in breast carcinoma in Jordan. Breast Cancer Research. 7, 598-604. http://dx.doi. breast-cancer-research.com/content/7/5/R598
Ayadi L, Khabir A, Amouri H, Karray SD, Abdallah GM, Boudawara T. 2008. Correlation of HER-2 overexpression with clinico pathological parameters in Tunisian breast carcinoma. World J. of Surgical Onc. 6: 112. http://dx.doi:10.1186/1477-7819-6-112
Zhou L, Yan TJ, Yiwei DG, Shen Z, Shao Z, Lu J. 2011. Prognostic and predictive value of TFF1 for adjuvant endocrine therapy in Chinese women with early ER positive breast cancer: Comparing aromatase inhibitors with tamoxifen. The Breast. 20: 15-20. http://dx.doi:10.1016/j.breast.2010.06.002
Allred DC, Harvey JM, Berardo M, Clark GM. 1998. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol. 11: 155-168.
Ribieras S, Tomasetto C, Rio. MC. 1998. The pS2/TFF1 trefoil factor, from basic research to clinical applications. Biochimica ET Biophysica Acta (BBA). 1378 (1): 61-77. http://dx.doi.org/10.1016/S0304-419X(98)00016-X
Huang H J, Neven P, Drijkoningen M, Paridaens R, Wildiers H, Van Limbergen E, Berteloot P, Amant F, Vergote I, Christiaens MR. 2005. Association between tumour characteristics and HER-2/neu by immunohistochemistry in 1362 women with primary operable breast cancer. J Clin Pathol. 58:611–616. https://dx.doi: 10.1136/jcp.2004.022772.x
Li A-q, Zhou Sl, Li M, Xu Y, Shui RH, Yu BH, Yang W. 2015. Clinicopathologic Characteristics of Oestrogen Receptor-Positive/Progesterone Receptor-Negative/Her2 Negative Breast Cancer According to a Novel Definition of Negative Progesterone Receptor Status: A Large Population-Based Study from China. PLoS ONE. 10(5):e0125067. https://dx.doi:10.1371/journal.pone.0125067.x
Hammond ME, Hayes DF, Wolff AC, Mangu PB, Temin S. 2010. American society of clinical oncology/college of American pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Oncol Pract. 6: 195-197.
Inaji H, Koyam H, Motomura K, Noguchi S. 1996. Differential distribution of ErbB-2 and pS2 proteins in ductal carcinoma in situ of the breast. Breast Cancer Res Treat. 37(1): 89-92. F. D. Doula et al. / JABS, 12 (1): 41-45, 2018, www.nobel.gen.tr 45
Pichon MF. and Milgrom E. 1993. Clinical significance of the estrogen regulated pS2 protein in mammary tumors. Oncology/Hematology. I5: 13-21.
Crosier M, Scott D, Ronald GW, CLIVE D, GRIFFITHS M, MAY FEB, Bruce RW. 2001. High Expression of the Trefoil Protein TFF1 in Interval Breast Cancers. American Journal of Pathology. 159(1): 215-221.
Rio MC, Bellocq JP, Gairard B, Rasmussen UB, Krust A, Koehl C, Calderoli H, Schiff V, Renaud R, Chambon P. 1987. Specific expression of the pS2 gene in subclasses of breast cancers in comparison with expression of the estrogen and progesterone receptors and the oncogene ERBB2. Proc. Natl Acad. Sci. 84: 9243-9247.
Amiry N, Kong X, Muniraj N, Kannan N, Grandison P.M, Lin J, Yang Y, Vouyovitch CM, Borges S, Perry J K, Mertani HC, Zhu T, Liu D, Lobie PE. 2011. Trefoil Factor-1 (TFF1) Enhances Oncogenicity of Mammary Carcinoma Cells. Endocrinology. 150 (10):4473-4483. https://dx. doi: 10.1210/en.2009-0066.x
Andrew DJ. And Ewald AJ. 2010. Morphogenesis of epithelial tubes: Insights into tube formation, elongation, and elaboration. Dev Biol. 341: 34–55.
Markicevic M, Dzodic R, Buta M, Buta M, Kanjer K, Mandusic V, Neskovic-Konstantinovic Z, Nikolic-Vukosavljevic D. 2014. Trefoil Factor 1 in Early Breast Carcinoma: A Potential Indicator of Clinical Outcome during the First 3 Years of Follow-Up. Int. J. Med. Sci. 11(7), 663-673. https:// doi: 10.7150/ijms.8194