Abstract
Fas (CD95-APO-1), a member of tumor necrosis factor receptor super-family, exists in two forms, transmembrane and soluble (sFas). It had been suggested that circulating sFas levels and/or tissue FasL may reflect the severity of invasive breast ductal carcinoma. Few studies showed that neither DNA-index nor ploidy is an independent prognostic indicator, and there is no correlation with clinical outcome. The S-phase fraction (SPF) has been shown to be useful prognostic factor in both node-negative and node-positive tumors. The present work was done to find a correlation between sFas, tissue FasL, ploidy and SPF with prognostic factors and survival of breast ductal carcinoma patients. The present study included two groups; a patients group comprised 30 patients with breast ductal carcinoma and a control group that comprised 15 patients with benign breast swellings. Serum sFas was measured using commercially available ELISA kit and tissue FasL expression was studied using avidin–biotine immunohistochemical staining technique. Cell cycle studies were performed using flow cytometry. Serum sFas was significantly higher in breast ductal carcinoma group than in the benign breast swelling control group. A significant negative correlation between serum sFas and overall survival was found. Tissue FasL expression was directly correlated with distant metastasis and poor overall survival. A significant direct correlation was found between moderate and high SPF with worse pathologic parameters. Serum sFas level, tissue FasL immuno-expression and S-phase fraction are independent prognostic factors in breast ductal carcinoma cases.
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References
Reed JC (2000) Mechanisms of apoptosis. Am J Pathol 156:1415–1430
Saas P, Walker PR, Hahne M et al (1997) Fas ligand expression by astrocytoma in vivo: maintaining immune privilege in the brain? J Clin Invest 99:1173–1178
Schneioer P, Bodmer JL, Holler N et al (1997) Characterization of Fas (Apo-1, CD95)-Fas ligand interaction. J Biol Chem 272:18827–18833
Griffith TS, Ferguson TA (1997) The role of FasL induced apoptosis in immune privilege. Immunol Today 18:2240–2244
Müschen M, Moers C, Warskulat U, Even J, Niederacher D, Beckmann MW (2000) CD95 ligand expression as a mechanism of immune escape in breast cancer. Immunology 99(1):69–77
Sheen-Chen SM, Chen HS, Eng HL, Chen WJ (2003) Circulating soluble Fas in patients with breast cancer. World J Surg 27(1):10–13, Jan
Suda T, Takahashi T, Golstein P, Nagata S (1993) Molecular cloning and expression of the Fas ligand: a novel member of the tumor necrosis factor family. Cell 75:1169–1186
Keane MM, Ettenberg SA, Lowrey GA, Russell EK, Lipkowitz S (1996) Fas expression and function in normal and malignant breast cell lines. Cancer Res 56:4791–4798
Harrnring C, Reimer T, Jeschke U, Makovitzky J, Kruger K, Gerber B, Kabelitz D, Friese K (2000) Expression of the apoptosis-inducing ligands FasL and TRAIL in malignant and benign human breast tumors. Histochem Cell Biol 113:189–194
Mullauer L, Mosberger I, Grusch M, Rudas M, Chott A (2000) Fas ligand is expressed in normal breast epithelial cells and is frequently upregulated in breast cancer. J Pathol 190:20–30
Mann B, Gratchev A, Bohm C et al (1999) FasL is more frequently expressed in liver metastases of colorectal cancer than in matched primary carcinomas. Br J Cancer 79:1262–1269
Munakata S, Enomoto T, Tsujimoto M et al (2000) Expression of Fas ligand and other apoptosis-related genes and their prognostic significance in epithelial ovarian neoplasms. Br J Cancer 82:1446–1452
Nagashima H, Mori M, Sadanaga N et al (2001) Expression of Fas ligand in gastric carcinoma relates to lymph node metastasis. Int J Oncol 18:1157–1162
Munakata S, Watanabe O, Ohashi K, Morino H (2005) Expression of Fas ligand and bcl-2 in cervical carcinoma and their prognostic significance. Am J Clin Pathol 123(6):879–885
Gatierrez LS, Eliza M, Niven-Fairchild T, Naftolin F, Mor G (1999) The Fas/Fas-ligand system: a mechanism for immune evasion in human breast carcinomas. Breast Cancer Res Treat 54(3):245–253
Robert I (2002) New concepts for the study of anticancer drug resistance [French]. Bull. Cancer 89:17–22
Hortobagyi GN (2001) Adjuvant systemic therapy for early breast cancer: progress and controversies. Clin Cancer Res 7:1839–1842
Ross JS, Linette GP, Stec J, Ross MS, Anwar S, Boguniewicz A (2003) DNA ploidy and cell cycle analysis in breast cancer. Am J Clin Pathol 120(Suppl):S72–S84, (ISSN: 0002-9173)
Chávez-Uribe EM, Viñuela JE, Cameselle-Teijeiro J, Forteza J, Puñal JA, Otero IL, Puente-Dominguez JL (2002) DNA ploidy and cytonuclear area of peritumoral and paratumoral samples of mastectomy specimens: a useful prognostic marker? Eur J Surg 168(1):37–41
Chassevent A, Jourdan ML, Romain S et al (2001) S-phase fraction and DNA ploidy in 633 T1T2 breast cancers: a standardized flow cytometric study. Clin Cancer Res 7(4):909–917, (ISSN: 1078-0432)
Greene FL, Page DL, Fleming ID et al (2002) Breast IN: American joint committee on cancer, AJCC cancer staging manual, 6th edn. Springer, New York, p 171
Burtis CA, Ashwood ER, Bruns DE (2006) Teitz text book of clinical chemistry and molecular diagnostics, 4th edn. Elsevier Saunders, St Louis, pp 870–871, 797–803, 582–590, 546–549, 604–611, 1892–1904 & 1698
Bouillon R, Coopman SW, Degroote DEH, Eliard PH (1990) Immunoradiometric assay of parathyrin polyclonal and monoclonal region specific antibodies. Clin Chem 36(2):271–276
Chen J, Zhou T, Liu C, Shapiro JP, Brauuer MJ, Kieler MC (1994) Protection from Fas-mediated apoptosis by a soluble form of the Fas molecule. Science 263:1759–1762
Chamness GC, McGuire WL (1979) Methods for analyzing steroid receptors in human breast cancer. In: McGuire WL (ed) Breast cancer. Advances in research and treatment. Plenum, New York, p 149
Bębenek M, Duś D, Koźlak J (2006) Fas and Fas ligand as prognostic factors in human breast carcinoma. Med Sci Monit 12(11):CR457–CR461
Almasri NM, 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 Res 7:R598–R604
Feichter GE, Müller A, Kaufmann M et al (1988) Correlation of DNA flow cytometric results and other prognostic factors in primary breast cancer. Int J Cancer 41:823–828
Feichter GE, Kaufmann M, Müller A et al (1989) DNA index and cell cycle analysis of primary breast cancer and synchronous axillary lymph node metastases. Breast Cancer Res Treat 13:17–22
Konrey GG, Pegram MD, Beryt M et al (1999) Therapeutic advantage of chemotherapy drugs in combination with herceptin against human breast cancer cells with HER-2/neu overexpression. Breast Cancer Res Treat 57:114
Kev TJ, Verkasalo PK, Banks E (2001) Epidemiology in breast cancer. Lancet Oncol 2(3):133–140
Reeves GK, Beral V, Green J, Gathan T, Bull D (2006) Hormonal therapy of menopause and breast-cancer risk by histological type: a cohort study and meta-analysis. Lancet Oncol 7(11):910–918
Jager JJ, Jansen RL, Arendo JW (2002) Clinical relevance of apoptotic markers in breast cancer is not yet clear. Apoptosis 7:361–365
Zhang L, Levi E, Majumder P, Yu Y, Aboukameel A, Du J (2007) Transactivator of transcription-tagged cell cycle and apoptosis regulatory protein-1 peptides suppress the growth of human breast cancer cells in vitro and in vivo. Mol Cancer Ther 6:1661–1672
Motyl T, Gajkowska B, Zarzy J, Gajewska M, Lamparska P (2006) Apoptosis and autophagy in mammary gland remodeling and breast cancer chemotherapy. J Physiol Pharmacol 7:17–32
Sheen-Chen SM, Chen HS, Eng HL, Chenw J (2003) Circulating soluble Fas in patients with breast cancer. World J Surg 27:10–13
Djerbi M, Screpanti Y, Catrini A et al (1999) The inhibitor of death receptor signaling. FLICE inhibitory protein defines a new class of tumor progression factors. J Exp Med 190:1025–1031
Nemesansky E, Tasnadi K, Juhasz P (1971) Diagnostic value of alkaline phosphatase isoenzyme in cancer patients. Cancer 27:1388–1397
Kao P, Cmklee GG, Taylor R, Heath H (1990) Parathyroid hormone related peptide in plasma of patients with hypercalcaemia and malignant lesions. Mayo Clin Proc 65:1399–1407
Koomagi R, Volm M (1999) Expression of Fas (CD95/APO-1) and Fas ligand in lung cancer, its prognostic and predictive relevance. Int J Cancer 84:239–243
Nagao M, Nakajima Y, Hisanaga M et al (1999) The alteration of Fas receptor and ligand system in hepatocellular carcinoma: how do hepatoma cells escape from the host immune surveillance in vivo? Hepatology 30:413–421
Shibakita M, Tachibana M, Dahr DK et al (1999) Prognostic significance of Fas and Fas ligand expression in human esophageal cancer. Clin Cancer Res 5:2464–2469
Ohno S, Tachibana M, Shibakita M et al (2000) Prognostic significance of Fas and Fas ligand system-associated apoptosis in gastric cancer. Ann Surg Oncol 7:750–757
Mottolese M, Buglioni S, Bracalenti C et al (2000) Prognostic relevance of altered Fas (CD95)-system in human breast cancer. Int J Cancer 89:127–132
Bebenek M, Duś D, Koźlak J (2007) Fas/Fas-ligand expressions in primary breast cancer are significant predictors of its skeletal spread. Anticancer Res 27(1A):215–218
Sjöström J, Blomqvist C, Boguslawski K et al (2002) The predictive value of bcl-2, bcl-xL, bag-1, Fas, and FasL for chemotherapy response in advanced breast cancer. Clin Cancer Res 8:811–816
Kute TE, Quadri Y, Muss H et al (1995) Flow cytometry in node-positive breast cancer: cancer and leukemia group B protocol 8869. Cytometry 22:297–306
Bryant J, Fisher B, Gunduz N et al (1998) S-phase fraction combined with other patient and tumor characteristics for the prognosis of node-negative, estrogen-receptor positive breast cancer. Breast Cancer Res Treat 51:239–253
Toikkanen S, Pylkkanen L, Joensuu H (1997) Invasive lobular carcinoma of the breast has better short- and long-term survival then invasive ductal carcinoma. Br J Cancer 76:1234–1240
Remvikos Y, Magdelenat H, Dutrillaux B (1995) Genetic evolution of breast cancers. III. Age-dependent variations in the correlations between biological indicators of prognosis. Breast Cancer Res Treat 34:25–33
Leonardi E, Cristofori A, Caffo O, Dalla Palma P (1997) Cytometric DNA analysis and prognostic biomarkers in breast carcinoma. Expression of P53 product in the different ploidy classes. Anal Cell Pathol 15:31–45
Dettmar P, Harbeck N, Thomssen C et al (1997) Prognostic impact of proliferation-associated factors MIB1 (Ki67) and s-phase fraction in node-negative breast cancer. Br J Cancer 75:1525–1533
Rudolph P, Alm P, Heidebrech H et al (1999) Immunologic proliferation marker Ki-S2 as prognostic indicator for lymph node-negative breast cancer. Natl Cancer Inst (Bethesda) 91:271–278
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El-Sarha, A.I., Magour, G.M., Zaki, S.M. et al. Serum sFas and Tumor Tissue FasL Negatively Correlated with Survival in Egyptian Patients Suffering from Breast Ductal Carcinoma. Pathol. Oncol. Res. 15, 241–250 (2009). https://doi.org/10.1007/s12253-008-9109-x
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DOI: https://doi.org/10.1007/s12253-008-9109-x