Cytology and Genetics

, Volume 50, Issue 1, pp 32–41 | Cite as

Immunohistochemical and biochemical analysis of mammary gland tumours of different age patients

  • T. LykholatEmail author
  • O. Lykholat
  • S. Antonyuk


Immunohistochemical and biochemical study of infiltrative ductal breast carcinoma and tissue adjacent to the tumour revealed a particular molecular profile and characteristics of the oxidant-antioxidant status neoplasms depending on the age of the patients and the presence of metastases in regional lymph nodes. Some causes of high aggressiveness and low hormone sensitivity of tumours in premenopausal women, as well as stability and high metastatic potential of tumours in postmenopausal women have been found.


breast tumours the molecular profile oxidant-antioxidant characteristics metastasis menopausal status 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Siegel, R., Naishadham, D., and Jemal, A., Cancer statistics, CA Cancer J. Clin., 2013, vol. 63, no. 1, pp. 11–30.CrossRefPubMedGoogle Scholar
  2. 2.
    Youlden, D.R., Cramb, S.M., Yip, C.H., and Baade, P.D., Incidence and mortality of female breast cancer in the Asia–Pacific region, Cancer Biol. Med., 2014, vol. 11, no. 2, pp. 101–115.PubMedCentralPubMedGoogle Scholar
  3. 3.
    Recchia, F., Candeloro, G., Desideri, G., Necozione, S., Recchia, C.O., Cirulli, V., and Rea, S., Triplenegative breast cancer: multipronged approach, singlearm pilot phase II study, Cancer Med., 2012, vol. 1, no. 1, pp. 89–95.PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    Bhikoo, R., Srinivasa, S., Yu, T.C., Moss, D., and Hill, A.G., Systematic review of breast cancer biology in developing countries (part 2): Asian subcontinent and South East Asia, Cancers (Basel), 2011, vol. 3, pp. 2382–2401.PubMedCentralCrossRefPubMedGoogle Scholar
  5. 5.
    Gonzalez-Angulo, A.M., Morales-Vasquez, F., and Hortobagyi, G.N., Overview of resistance to systemic therapy in patients with breast cancer, Adv. Exp. Med. Biol., 2007, vol. 608, pp. 1–22.CrossRefPubMedGoogle Scholar
  6. 6.
    Fernández, A., Giménez, N., Fraile, M., González, S., Chabrera, C., Torras, M., Gonzalez, C., Salas, A., Barco, I., Cirera, L., Cambra, M.J., Veloso, E., and Pessarrodona, A., Survival and clinicopathological characteristics of breast cancer patient according to different tumour subtypes as determined by hormone receptor and Her2 immunohistochemistry. A single institution survey spanning 1998 to 2010, Breast, 2012, vol. 21, no. 3, pp. 366–373.CrossRefGoogle Scholar
  7. 7.
    Hosoda, M., Yamamoto, M., Nakano, K., Hatanaka, K.C., Takakuwa, E., Hatanaka, Y., Matsuno, Y., and Yamashita, H., Differential expression of progesterone receptor, FOXA1, GATA3, and p53 between preand postmenopausal women with estrogen receptor-positive breast cancer, Breast Cancer Res. Treat., 2014, vol. 144, no. 2, pp. 249–261.CrossRefPubMedGoogle Scholar
  8. 8.
    Reddy, K.B., Triple-negative breast cancers: an updated review on treatment options, Curr. Oncol., 2011, vol. 18, no. 4, pp. 173–179.CrossRefGoogle Scholar
  9. 9.
    Recchia, F., Candeloro, G., Necozione, S., Desideri, G., Recchia, C.O., Piazze, J., and Rea, S., Premenopausal hormone-responsive breast cancer with extensive axillary nodes involvement: total estrogen blockade and chemotherapy, Anticancer Res., 2011, vol. 31, no. 2, pp. 671–676.PubMedGoogle Scholar
  10. 10.
    Tummers, Q.R., Verbeek, F.P., Schaafsma, B.E., Boonstra, M.C., van der Vorst, J.R., Liefers, G.J., van de Velde, C.J., Frangioni, J.V., and Vahrmeijer, A.L., Real-time intraoperative detection of breast cancer using near-infrared fluorescence imaging and methylene blue, Eur. J. Surg. Oncol., 2014, vol. 40, no. 7, pp. 850–858.PubMedCentralCrossRefPubMedGoogle Scholar
  11. 11.
    Slamon, D.J., Leyland-Jones, B., Shak, S., Fuchs, H., Paton, V., Bajamonde, A., Fleming, T., Eierma, W., Wolter, J., Pegram, M., Baselga, J., and Norton, L., Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2, N. Engl. J. Med., 2001, vol. 344, no. 11, pp. 783–792.CrossRefPubMedGoogle Scholar
  12. 12.
    Di Gioia, D., Dresse, M., Mayr, D., Nagel, D., Heinemann, V., and Stieber, P., Serum HER2 in combination with CA 15-3 as a parameter for prognosis in patients with early breast cancer, Clin. Chim. Acta, 2015, vol. 440, pp. 16–22.CrossRefPubMedGoogle Scholar
  13. 13.
    Rakha, E.A., Starczynski, J., Lee, A.H., and Ellis, I.O., The updated ASCO/CAP guideline recommendations for HER2 testing in the management of invasive breast cancer: a critical review of their implications for routine practice, Histopathology, 2014, vol. 64, no. 5, pp. 609–615.CrossRefPubMedGoogle Scholar
  14. 14.
    Harari, D. and Yarden, Y., Molecular mechanism underlaying Erbb/HER2 action in breast cancer, Oncogene, 2000, vol. 19, no. 53, pp. 6102–6114.CrossRefPubMedGoogle Scholar
  15. 15.
    Mass, R., The role of her-2 expression in predicting response to therapy in breast cancer, Semin. Oncol., 2000, vol. 27, suppl. 11, pp. 46–52.PubMedGoogle Scholar
  16. 16.
    Walker, R.A., Harris, A.L., and Balslev, E., Immunohistochemistry and Breast Cancer. Diagnosis, Therapy and Prognosis, Corporate Headquartes Denmark, 2004.Google Scholar
  17. 17.
    Press, M.F., Bernstein, L., Thomas, P.A., Meisner, L.F., Zhou, J.Y., Ma, Y., Hung, G., Robinson, R.A., Harris, C., El-Naggar, A., Slamon, D.J., Phillips, R.N., Ross, J.S., Wolman, S.R., and Flom, K.J., HER-2/neu gene amplification characterized by fluorescence in situ hybridization: poor prognosis in node-negative breast carcinomas, J. Clin. Oncol., 1997, vol. 15, no. 8, pp. 2894–2904.PubMedGoogle Scholar
  18. 18.
    Pozharisskii, K.M. and Leenman, E.E., The role of immunohistochemical methods for determining the type of treatment and prognosis of tumoral disease, Arkh. Patol., 2000, vol. 62, no. 5, pp. 3–11.PubMedGoogle Scholar
  19. 19.
    Gu, J.W., Young, E., Busby, B., Covington, J., and Johnson, J.W., Oral administration of pyrrolidine dithiocarbamate (PDTC) inhibits VEGF expression, tumor angiogenesis, and growth of breast cancer in female, Cancer Biol. Ther., 2009, vol. 8, no. 6, pp. 514–521.CrossRefPubMedGoogle Scholar
  20. 20.
    Panis, C., Victorino, V.J., Herrera, A.C., Freitas, L.F., De Rossi, T., Campos, F.C., Simao, A.N., Barbosa, D.S., Pinge-Filho, P., Cecchini, R., and Cecchini, A.L., Differential oxidative status and immune characterization of the early and advanced stages of human breast cancer, Breast Cancer Res. Treat., 2012, vol. 133, no. 3, pp. 881–888.CrossRefPubMedGoogle Scholar
  21. 21.
    Giordano, C.R., Mueller, K.L., Terlecky, L.J., Krentz, K.A., Bollig-Fischer, A., Terlecky, S.R., and Boerner, J.L., A targeted enzyme approach to sensitization of tyrosine kinase inhibitor-resistant breast cancer cells, Exp. Cell Res., 2012, vol. 318, no. 16, pp. 2014–2021.CrossRefPubMedGoogle Scholar
  22. 22.
    Himmetoglu, S., Dincer, Y., Ersoy, Y.E., Bayraktar, B., Celik, V., and Akcay, T., DNA oxidation and antioxidant status in breast cancer, J. Investig. Med., 2009, vol. 57, no. 6, pp. 720–723.PubMedGoogle Scholar
  23. 23.
    Chua, P.J., Yip, G.W., and Bay, B.H., Cell cycle arrest induced by hydrogen peroxide is associated with modulation of oxidative stress related genes in breast cancer cells, Exp. Biol. Med. (Maywood), 2009, vol. 234, no. 9, pp. 1086–1094.CrossRefGoogle Scholar
  24. 24.
    Papa, L. and Germain, D., Estrogen receptor mediates a distinct mitochondrial unfolded protein response, J. Cell Sci., 2011, vol. 124, pp. 1396–1402.PubMedCentralCrossRefPubMedGoogle Scholar
  25. 25.
    Mercier, I., Camacho, J., Titchen, K., Gonzales, D.M., Quann, K., Bryant, K.G., Molchansky, A., Milliman, J.N., Whitaker-Menezes, D., Sotgia, F., Jasmin, J.F., Schwarting, R., Pestell, R.G., Blagosklonny, M.V., and Lisanti, M.P., Caveolin-1 and accelerated host aging in the breast tumor microenvironment: chemoprevention with rapamycin, an mTOR inhibitor and anti-aging drug, Am. J. Pathol., 2012, vol. 181, no. 1, pp. 278–293.PubMedCentralCrossRefPubMedGoogle Scholar
  26. 26.
    Gerber, M. and Segala, C., Aging and cancer: plasma antioxidants and lipid peroxidation in young and aged breast cancer patients, in Free Radicals and Aging, Emerit, I. and Chance, B., Eds., Birkhauser, 2013, pp. 235–246.Google Scholar
  27. 27.
    Kasapovic, J., Pejic, S., Stojiljkovic, V., Todorovic, A., Radosevic-Jelic, L., Saicic, Z.S., and Pajovic, S.B., Antioxidant status and lipid peroxidation in the blood of breast cancer patients of different ages after chemotherapy with 5-fluorouracil, doxorubicin and cyclophosphamide, Clin. Biochem., 2010, vol. 43, nos. 16–17, pp. 1287–1293.CrossRefPubMedGoogle Scholar
  28. 28.
    Petrov, S.V. and Rayhlyn, N.T., Guide to Immunohistochemical Diagnosis of Human Tumours, Kazan, 2004.Google Scholar
  29. 29.
    Huang, H.J., Neven, P., Drijkoningen, M., Paridaens, R., Wildiers, H., Van Limbergen, E., Berteloot, P., Amant, F., Vergote, I., and Christiaens, M.R., Association between tumour characteristics and HER-2/neu by immunohistochemistry in 1362 women with primary operable breast cancer, J. Clin. Pathol., 2005, vol. 58, no. 6, pp. 611–616.PubMedCentralCrossRefPubMedGoogle Scholar
  30. 30.
    Korobeinikova, E.N., Modification of the method for determining TBA-active products, Lab. Delo, 1989, no. 7, pp. 8–9.PubMedGoogle Scholar
  31. 31.
    Klebanov, G.I., Babenkova, I.V., and Teselkin, J.O., Evaluation of the antioxidant activity of blood plasma using yolk lipoprotein, Lab. Delo, 1988, no. 5, pp. 59–62.PubMedGoogle Scholar
  32. 32.
    Owens, C.W.I. and Belcher, R.V., A colorimetric micro-method for determination of glutathione, Biochem. J., 1965, vol. 94, pp. 705–711.PubMedCentralCrossRefPubMedGoogle Scholar
  33. 33.
    Pereslegina, I.A., Activity of antioxidant enzymes of saliva of healthy, Lab. Delo, 1989, no. 11, pp. 20–23.PubMedGoogle Scholar
  34. 34.
    Habdous, M., Vincent-Viry, M., Visvikis, S., and Siest, G., Rapid spectrophotometric method for serum glutathione S-transferases activity, Clin. Chim. Acta, 2002, vol. 326, nos. 1–2, pp. 131–142.CrossRefPubMedGoogle Scholar
  35. 35.
    Razygraev, A.V., Glutathione peroxidase activity in the tissue of the rat pineal gland and its changes during aging, Adv. Gerontology, 2010, vol. 23, no. 3, pp. 392–395.Google Scholar
  36. 36.
    Lowry, O.H., Rosenbrough, N.J., Farr, A.L., and Randall, R.J., Protein measurement with the Folin phenol reagent, J. Biol. Chem., 1951, vol. 193, no. 1, pp. 265–275.PubMedGoogle Scholar
  37. 37.
    Kamarajugadda, S., Cai, Q., Chen, H., Nayak, S., Zhu, J., He, M., Jin, Y., Zhang, Y., Ai, L., Martin, S.S., Tan, M., and Lu, J., Manganese superoxide dismutase promotes anoikis resistance and tumor metastasis, Cell Death Dis., 2013, vol. 4, p. e504.PubMedCentralCrossRefPubMedGoogle Scholar
  38. 38.
    Filipovic, S., Kocic, B., and Petrovic, B., Hormone sensitivity of primary breast carcinoma, J. BUON, 2010, vol. 15, no. 2, pp. 255–262.PubMedGoogle Scholar
  39. 39.
    Broom, R.J., Tang, P.A., Simmons, C., Bordeleau, L., Mulligan, A.M., O’Malley, F.P., Miller, N., Andrulis, L., Brenner, D.M., and Clemons, M.J., Changes in oestrogen receptor, progesterone receptor and Her-2/neu status with time: discordance rates between primary and metastatic breast cancer, Anticancer Res., 2009, vol. 29, no. 5, pp. 1557–1562.PubMedGoogle Scholar
  40. 40.
    Cortez, V., Mann, M., Brann, D.W., and Vadlamudi, R.K., Extranuclear signaling by estrogen: role in breast cancer progression and metastasis, Minerva Ginecol., 2010, vol. 62, no. 6, pp. 573–583.PubMedCentralPubMedGoogle Scholar
  41. 41.
    Wang, S.L., Li, Y.X., Song, Y.W., Wang, W.H., Jin, J., Liu, Y.P., Liu, X.F., and Yu, Z.H., Prognostic value of estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 in node positive breast cancer patients treated by mastectomy, Zhonghua Zhong Liu Za Zhi, 2010, vol. 32, no. 7, pp. 520–525.PubMedGoogle Scholar
  42. 42.
    Harrell, J.C., Dye, W.W., Harvell, D.M., Pinto, M., Jedlicka, P., Sartorius, C.A., and Horwitz, K.B., Estrogen insensitivity in a model of estrogen receptor positive breast cancer lymph node metastasis, Cancer Res., 2007, vol. 67, no. 21, pp. 10582–10591.CrossRefPubMedGoogle Scholar
  43. 43.
    Finn, R.S., Press, M.F., Dering, J., Arbushites, M., Koehler, M., Oliva, C., Williams, L.S., and Di Leo, A., Estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2), and epidermal growth factor receptor expression and benefit from lapatinib in a randomized trial of paclitaxel with lapatinib orplacebo as first-line treatment in HER2-negative or unknown metastatic breast cancer, J. Clin. Oncol., 2009, vol. 27, no. 24, pp. 3908–3915.PubMedCentralCrossRefPubMedGoogle Scholar
  44. 44.
    Arpino, G., Weiss, H., Lee, A.V., Schiff, R., De Placido, S., Osborne, C.K., and Elledge, R.M., Estrogen receptor-positive, progesterone receptor-negative breast cancer: association with growth factor receptor expression and tamoxifen resistance, J. Natl. Cancer Inst., 2005, vol. 97, no. 17, pp. 1254–1261.CrossRefPubMedGoogle Scholar
  45. 45.
    Darb-Esfahani, S., Loibl, S., Muller, B.M., Roller, M., Denkert, C., Komor, M., Schluns, K., Blohmer, J.U., Budczies, J., Gerber, B., Noske, A., Bois, A., Weichert, W., Jackisch, C., Dietel, M., Richter, K., Kaufmann, M., and von Minckwitz, G., Identification of biology-based breast cancer types with distinct predictive and prognostic features: role of steroid hormone and HER2 receptor expression in patients treated with neoadjuvant anthracycline/taxane-based chemotherapy, Breast Cancer Res., 2009, vol. 11, no. 5, p. R69.PubMedCentralCrossRefPubMedGoogle Scholar
  46. 46.
    Rajneesh, C.P., Manimaran, A., Sasikala, K.R., and Adaikappan, P., Lipid peroxidation and antioxidant status in patients with breast cancer, Singapore Med. J., 2008, vol. 49, no. 8, pp. 640–643.PubMedGoogle Scholar
  47. 47.
    Kyndi, M., Sørensen, F.B., Knudsen, H., Overgaard, M., Nielsen, H.M., and Overgaard, J., Estrogen receptor, progesterone receptor, HER-2, and response to postmastectomy radiotherapy in high-risk breast cancer: the Danish breast cancer cooperative group, J. Clin. Oncol., 2008, vol. 26, no. 9, pp. 1419–1426.CrossRefPubMedGoogle Scholar
  48. 48.
    Echiburú-Chau, C., Roy, D., and Calaf, G.M., Metastatic suppressor CD44 is related with oxidative stress in breast cancer cell lines, Int. J. Oncol., 2011, vol. 39, no. 6, pp. 1481–1489.PubMedGoogle Scholar

Copyright information

© Allerton Press, Inc. 2016

Authors and Affiliations

  1. 1.Oles Honchar Dnipropetrovsk National UniversityDnipropetrovskUkraine
  2. 2.University Customs Business and FinanceDnipropetrovskUkraine
  3. 3.Regional Cancer CentreDnipropetrovskUkraine

Personalised recommendations