Why is Immunohistochemical Detection of Metastasized Breast Cancer Cells in the Immunocompetent Host Not Always Easy?
DOI:
https://doi.org/10.30683/1927-7229.2018.07.04.2Keywords:
Breast cancer, metastasis, genotypic and phenotypic changes.Abstract
Metastases of breast cancer cells from the tissue of origin to distant sites including vital organs commonly occurs in patients suffering from breast cancer. Such metastases are detrimental to the quality of life of these patients. Clinical pathologists and basic researchers in the field of oncology commonly use techniques like immunohistochemistry to detect disseminated cancer cells in metastasized regions in an attempt to improve patient outcomes. This review sheds light on genotypic and phenotypic changes in disseminated cancer cells that occur during the ongoing process of metastasis, thereby leading to continuous changes in the expression levels of different markers expressed by these cells and making the immunohistochemical detection of breast cancer cells in the non-cognate tissues difficult.
References
Stelow EB, Yaziji H. Immunohistochemistry, carcinomas of unknown primary, and incidence rates. Seminars in diagnostic pathology 2018; 35: 143-152. https://doi.org/10.1053/j.semdp.2017.11.012 DOI: https://doi.org/10.1053/j.semdp.2017.11.012
Slade MJ, Coombes RC. The clinical significance of disseminated tumor cells in breast cancer. Nat Clin Prac Oncol 2007; 4: 30-41. https://doi.org/10.1038/ncponc0685 DOI: https://doi.org/10.1038/ncponc0685
Allott EH, Geradts J, Sun X, Cohen SM, Zirpoli GR, Khoury T, Bshara W, Chen M, Sherman ME, Palmer JR, Ambrosone CB, Olshan AF, Troester MA. Intratumoral heterogeneity as a source of discordance in breast cancer biomarker classification. Breast Cancer Research 2016; 18: 1-11. https://doi.org/10.1186/s13058-016-0725-1 DOI: https://doi.org/10.1186/s13058-016-0725-1
Bedard PL, Hansen AR, Ratain MJ, Siu LL. Tumour heterogeneity in the clinic. Nature 2013; 501: 355-364. https://doi.org/10.1038/nature12627 DOI: https://doi.org/10.1038/nature12627
Sturgeon CM, Duffy MJ, Stenman U-H, Lilja H, Brünner N, Chan DW, Babaian R, Bast RC, Dowell B, Esteva FJ, Haglund C, Harbeck N, Hayes DF, Holten-Andersen M, Klee GG, Lamerz R, Looijenga LH, Molina R, Nielsen HJ, Rittenhouse H, Semjonow A, Shih I-M, Sibley P, Sölétormos G, Stephan C, Sokoll L, Hoffman BR, Diamandis EP. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Testicular, Prostate, Colorectal, Breast, and Ovarian Cancers. Clinical Chemistry 2008; 54: e11-e79. DOI: https://doi.org/10.1373/clinchem.2008.105601
Olofsson MH, Ueno T, Pan Y, Xu R, Cai F, van der Kuip H, Muerdter TE, Sonnenberg M, Aulitzky WE, Schwarz S, Andersson E, Shoshan MC, Havelka AM, Toi M, Linder S. Cytokeratin-18 is a useful serum biomarker for early determination of response of breast carcinomas to chemotherapy. Clinical cancer research : an official journal of the American Association for Cancer Research 2007; 13: 3198-3206. https://doi.org/10.1158/1078-0432.CCR-07-0009 DOI: https://doi.org/10.1158/1078-0432.CCR-07-0009
Buckley NE, Forde C, McArt DG, Boyle DP, Mullan PB, James JA, Maxwell P, McQuaid S, Salto-Tellez M. Quantification of HER2 heterogeneity in breast cancer–implications for identification of sub-dominant clones for personalised treatment. Scientific reports 2016; 6 DOI: https://doi.org/10.1038/srep23383
Kurozumi S, Padilla M, Kurosumi M, Matsumoto H, Inoue K, Horiguchi J, Takeyoshi I, Oyama T, Ranger-Moore J, Allred DC, Dennis E, Nitta H. HER2 intratumoral heterogeneity analyses by concurrent HER2 gene and protein assessment for the prognosis of HER2 negative invasive breast cancer patients. Breast cancer research and treatment 2016; 158: 99-111. https://doi.org/10.1007/s10549-016-3856-2 DOI: https://doi.org/10.1007/s10549-016-3856-2
Onsum MD, Geretti E, Paragas V, Kudla AJ, Moulis SP, Luus L, Wickham TJ, McDonagh CF, Macbeath G, Hendriks BS. Single-cell quantitative HER2 measurement identifies heterogeneity and distinct subgroups within traditionally defined HER2-positive patients. Am J Pathol 2013; 183: 1446-1460. https://doi.org/10.1016/j.ajpath.2013.07.015 DOI: https://doi.org/10.1016/j.ajpath.2013.07.015
Rahn JJ, Dabbagh L, Pasdar M, Hugh JC. The importance of MUC1 cellular localization in patients with breast carcinoma. Cancer 2001; 91: 1973-1982. https://doi.org/10.1002/1097-0142(20010601)91:11<1973::AID-CNCR1222>3.0.CO;2-A DOI: https://doi.org/10.1002/1097-0142(20010601)91:11<1973::AID-CNCR1222>3.0.CO;2-A
Cimpean AM, Suciu C, Ceausu R, Tatucu D, Muresan AM, Raica M. Relevance of the immunohistochemical expression of cytokeratin 8/18 for the diagnosis and classification of breast cancer. Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie 2008; 49: 479-483.
Orito T, Shinohara H, Okada Y, Mori M. Heterogeneity of Keratin Expression in Epithelial Tumor Cells of Adenolymphoma in Paraffin Sections. Pathology - Research and Practice 1989; 184: 600-608. https://doi.org/10.1016/S0344-0338(89)80165-7 DOI: https://doi.org/10.1016/S0344-0338(89)80165-7
Lichy JH, Dalbegue F, Zavar M, Washington C, Tsai MM, Sheng Z-M, Taubenberger JK. Genetic Heterogeneity in Ductal Carcinoma of the Breast. Laboratory investigation; a journal of technical methods and pathology 2000; 80: 291-301. https://doi.org/10.1038/labinvest.3780034 DOI: https://doi.org/10.1038/labinvest.3780034
Denisov EV, Litviakov NV, Zavyalova MV, Perelmuter VM, Vtorushin SV, Tsyganov MM, Gerashchenko TS, Garbukov EY, Slonimskaya EM, Cherdyntseva NV. Intratumoral morphological heterogeneity of breast cancer: neoadjuvant chemotherapy efficiency and multidrug resistance gene expression. Scientific reports 2014; 4: 4709. https://doi.org/10.1038/srep04709 DOI: https://doi.org/10.1038/srep04709
Hiley C, de Bruin EC, McGranahan N, Swanton C. Deciphering intratumor heterogeneity and temporal acquisition of driver events to refine precision medicine. Genome biology 2014; 15: 453. https://doi.org/10.1186/s13059-014-0453-8 DOI: https://doi.org/10.1186/s13059-014-0453-8
Badve S, Nakshatri H. Breast-cancer stem cells— beyond semantics. The Lancet Oncology 2012; 13: e43-e48. https://doi.org/10.1016/S1470-2045(11)70191-7 DOI: https://doi.org/10.1016/S1470-2045(11)70191-7
Marusyk A, Almendro V, Polyak K. Intra-tumour heterogeneity: a looking glass for cancer? Nature reviews Cancer 2012; 12: 323-334. https://doi.org/10.1038/nrc3261 DOI: https://doi.org/10.1038/nrc3261
Whitescarver J. Problems of In vitro Culture of Human Mammary Tumor Cells. Journal of Investigative Dermatology 1974; 63: 58-64. https://doi.org/10.1111/1523-1747.ep12678088 DOI: https://doi.org/10.1111/1523-1747.ep12678088
Hanahan D, Weinberg Robert A. Hallmarks of Cancer: The Next Generation. Cell 2011; 144: 646-674. https://doi.org/10.1016/j.cell.2011.02.013 DOI: https://doi.org/10.1016/j.cell.2011.02.013
Negrini S, Gorgoulis VG, Halazonetis TD. Genomic instability
Ferguson LR, Chen H, Collins AR, Connell M, Damia G, Dasgupta S, Malhotra M, Meeker AK, Amedei A, Amin A, Ashraf SS, Aquilano K, Azmi AS, Bhakta D, Bilsland A, Boosani CS, Chen S, Ciriolo MR, Fujii H, Guha G, Halicka D, Helferich WG, Keith WN, Mohammed SI, Niccolai E, Yang X, Honoki K, Parslow VR, Prakash S, Rezazadeh S, Shackelford RE, Sidransky D, Tran PT, Yang ES, Maxwell CA. Genomic instability in human cancer: Molecular insights and opportunities for therapeutic attack and prevention through diet and nutrition. Seminars in Cancer Biology 2015; 35: S5-S24. https://doi.org/10.1016/j.semcancer.2015.03.005 DOI: https://doi.org/10.1016/j.semcancer.2015.03.005
Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to tumor escape. Nature immunology 2002; 3: 991-998. https://doi.org/10.1038/ni1102-991 DOI: https://doi.org/10.1038/ni1102-991
Kmieciak M, Knutson KL, Dumur CI, Manjili MH. HER-2/neu antigen loss and relapse of mammary carcinoma are actively induced by T cell-mediated anti-tumor immune responses. European journal of immunology 2007; 37: 675-685. https://doi.org/10.1002/eji.200636639 DOI: https://doi.org/10.1002/eji.200636639
Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annual review of immunology 2004; 22: 329-360. https://doi.org/10.1146/annurev.immunol.22.012703.104803 DOI: https://doi.org/10.1146/annurev.immunol.22.012703.104803
Mohme M, Riethdorf S, Pantel K. Circulating and disseminated tumour cells
Sanchez-Perez L, Kottke T, Diaz RM, Ahmed A, Thompson J, Chong H, Melcher A, Holmen S, Daniels G, Vile RG. Potent Selection of Antigen Loss Variants of B16 Melanoma following Inflammatory Killing of Melanocytes In vivo. Cancer research 2005; 65: 2009-2017. https://doi.org/10.1158/0008-5472.CAN-04-3216 DOI: https://doi.org/10.1158/0008-5472.CAN-04-3216
Liu K, Caldwell SA, Abrams SI. Immune selection and emergence of aggressive tumor variants as negative consequences of Fas-mediated cytotoxicity and altered IFN-gamma-regulated gene expression. Cancer research 2005; 65: 4376-4388. https://doi.org/10.1158/0008-5472.CAN-04-4269 DOI: https://doi.org/10.1158/0008-5472.CAN-04-4269
Beatty GL, Paterson Y. IFN-gamma can promote tumor evasion of the immune system in vivo by down-regulating cellular levels of an endogenous tumor antigen. Journal of immunology (Baltimore, Md: 1950) 2000; 165: 5502-5508. DOI: https://doi.org/10.4049/jimmunol.165.10.5502
Beatty GL, Paterson Y. Regulation of tumor growth by IFN-gamma in cancer immunotherapy. Immunologic research 2001; 24: 201-210. https://doi.org/10.1385/IR:24:2:201 DOI: https://doi.org/10.1385/IR:24:2:201
Singh A, Sirohi B, Gupta S. Biomarkers in Breast Cancer and the Implications of Their Discordance. Current Breast Cancer Reports 2013; 5: 266-274. https://doi.org/10.1007/s12609-013-0126-8 DOI: https://doi.org/10.1007/s12609-013-0126-8
Thompson AM, Jordan LB, Quinlan P, Anderson E, Skene A, Dewar JA, Purdie CA. Prospective comparison of switches in biomarker status between primary and recurrent breast cancer: the Breast Recurrence In Tissues Study (BRITS). Breast cancer research : BCR 2010; 12: R92. DOI: https://doi.org/10.1186/bcr2771
Aktas B, Kasimir-Bauer S, Müller V, Janni W, Fehm T, Wallwiener D, Pantel K, Tewes M. Comparison of the HER2, estrogen and progesterone receptor expression profile of primary tumor, metastases and circulating tumor cells in metastatic breast cancer patients. BMC cancer 2016; 16 DOI: https://doi.org/10.1186/s12885-016-2587-4
Somlo G, Lau SK, Frankel P, Hsieh HB, Liu X, Yang L, Krivacic R, Bruce RH. Multiple biomarker expression on circulating tumor cells in comparison to tumor tissues from primary and metastatic sites in patients with locally advanced/inflammatory, and stage IV breast cancer, using a novel detection technology. Breast cancer research and treatment 2011; 128: 155-163. https://doi.org/10.1007/s10549-011-1508-0 DOI: https://doi.org/10.1007/s10549-011-1508-0
Millner LM, Linder MW, Valdes R, Jr. Circulating tumor cells: a review of present methods and the need to identify heterogeneous phenotypes. Ann Clin Lab Sci 2013; 43: 295-304.
Zhang C, Guan Y, Sun Y, Ai D, Guo Q. Tumor heterogeneity and circulating tumor cells. Cancer letters 2016; 374: 216-223. https://doi.org/10.1016/j.canlet.2016.02.024 DOI: https://doi.org/10.1016/j.canlet.2016.02.024
Vlems FA, Ruers TJM, Punt CJA, Wobbes T, van Muijen GNP. Relevance of disseminated tumour cells in blood and bone marrow of patients with solid epithelial tumours in perspective. European Journal of Surgical Oncology (EJSO) 2003; 29: 289-302. https://doi.org/10.1053/ejso.2002.1394 DOI: https://doi.org/10.1053/ejso.2002.1394
Deng G, Krishnakumar S, Powell AA, Zhang H, Mindrinos MN, Telli ML, Davis RW, Jeffrey SS. Single cell mutational analysis of PIK3CA in circulating tumor cells and metastases in breast cancer reveals heterogeneity, discordance, and mutation persistence in cultured disseminated tumor cells from bone marrow. BMC cancer 2014; 14: 456. https://doi.org/10.1186/1471-2407-14-456 DOI: https://doi.org/10.1186/1471-2407-14-456
Fehm T, Krawczyk N, Solomayer E-F, Becker-Pergola G, Dürr-Störzer S, Neubauer H, Seeger H, Staebler A, Wallwiener D, Becker S. ERalpha-status of disseminated tumour cells in bone marrow of primary breast cancer patients. Breast Cancer Research 2008; 10: 1-8. https://doi.org/10.1186/bcr1869 DOI: https://doi.org/10.1186/bcr2143
El Nemr Esmail RS, El Farouk Abdel-Salam LO, Abd El Ellah MM. Could the Breast Prognostic Biomarker Status Change During Disease Progression? An Immunohistochemical Comparison between Primary Tumors and Synchronous Nodal Metastasis. Asian Pacific journal of cancer prevention : APJCP 2015; 16: 4317-4321. https://doi.org/10.7314/APJCP.2015.16.10.4317 DOI: https://doi.org/10.7314/APJCP.2015.16.10.4317
Hanagiri T, Shigematsu Y, Shinohara S, Takenaka M, Oka S, Chikaishi Y, Nagata Y, Baba T, Uramoto H, So T, Yamada S. Clinical significance of expression of cancer/testis antigen and down-regulation of HLA class-I in patients with stage I non-small cell lung cancer. Anticancer research 2013; 33: 2123-2128.
Mendez R, Ruiz-Cabello F, Rodriguez T, Del Campo A, Paschen A, Schadendorf D, Garrido F. Identification of different tumor escape mechanisms in several metastases from a melanoma patient undergoing immunotherapy. Cancer immunology, immunotherapy : CII 2007; 56: 88-94. https://doi.org/10.1007/s00262-006-0166-2 DOI: https://doi.org/10.1007/s00262-006-0166-2
Rivoltini L, Carrabba M, Huber V, Castelli C, Novellino L, Dalerba P, Mortarini R, Arancia G, Anichini A, Fais S, Parmiani G. Immunity to cancer: attack and escape in T lymphocyte-tumor cell interaction. Immunological reviews 2002; 188: 97-113. https://doi.org/10.1034/j.1600-065X.2002.18809.x DOI: https://doi.org/10.1034/j.1600-065X.2002.18809.x
Knutson KL, Lu H, Stone B, Reiman JM, Behrens MD, Prosperi CM, Gad EA, Smorlesi A, Disis ML. Immunoediting of cancers may lead to epithelial to mesenchymal transition. Journal of immunology (Baltimore, Md: 1950) 2006; 177: 1526-1533. https://doi.org/10.4049/jimmunol.177.3.1526 DOI: https://doi.org/10.4049/jimmunol.177.3.1526
Gorges TM, Tinhofer I, Drosch M, Röse L, Zollner TM, Krahn T, von Ahsen O. Circulating tumour cells escape from EpCAM-based detection due to epithelial-to-mesenchymal transition. BMC cancer 2012; 12: 1-13. https://doi.org/10.1186/1471-2407-12-178 DOI: https://doi.org/10.1186/1471-2407-12-178
Larue L, Bellacosa A. Epithelial-mesenchymal transition in development and cancer: role of phosphatidylinositol 3
Voulgari A, Pintzas A. Epithelial–mesenchymal transition in cancer metastasis: Mechanisms, markers and strategies to overcome drug resistance in the clinic. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 2009; 1796: 75-90. https://doi.org/10.1016/j.bbcan.2009.03.002 DOI: https://doi.org/10.1016/j.bbcan.2009.03.002
Foroni C, Broggini M, Generali D, Damia G. Epithelial–mesenchymal transition and breast cancer: Role, molecular mechanisms and clinical impact. Cancer treatment reviews 2012; 38: 689-697. https://doi.org/10.1016/j.ctrv.2011.11.001 DOI: https://doi.org/10.1016/j.ctrv.2011.11.001
Wu Y, Sarkissyan M, Vadgama J. Epithelial-Mesenchymal Transition and Breast Cancer. Journal of Clinical Medicine 2016; 5: 13. https://doi.org/10.3390/jcm5020013 DOI: https://doi.org/10.3390/jcm5020013
Bill R, Christofori G. The relevance of EMT in breast cancer metastasis: Correlation or causality? FEBS letters 2015; 589: 1577-1587. https://doi.org/10.1016/j.febslet.2015.05.002 DOI: https://doi.org/10.1016/j.febslet.2015.05.002
Palma CdS, Grassi ML, Thomé CH, Ferreira GA, Albuquerque D, Pinto MT, Melo FUF, Kashima S, Covas DT, Pitteri SJ, Faca VM. Proteomic analysis of epithelial to mesenchymal transition reveals crosstalk between SNAIL and HDAC1 in breast cancer cells. Molecular & Cellular Proteomics 2016 DOI: https://doi.org/10.1074/mcp.M115.052910
Duffy MJ, Evoy D, McDermott EW. CA 15-3: Uses and limitation as a biomarker for breast cancer. Clinica Chimica Acta 2010; 411: 1869-1874. https://doi.org/10.1016/j.cca.2010.08.039 DOI: https://doi.org/10.1016/j.cca.2010.08.039
DeSouza MM, Mani SK, Julian J, Carson DD. Reduction of mucin-1 expression during the receptive phase in the rat uterus. Biology of reproduction 1998; 58: 1503-1507. https://doi.org/10.1095/biolreprod58.6.1503 DOI: https://doi.org/10.1095/biolreprod58.6.1503
Horne AW, Lalani EN, Margara RA, White JO. The effects of sex steroid hormones and interleukin-1-beta on MUC1 expression in endometrial epithelial cell lines. Reproduction (Cambridge, England) 2006; 131: 733-742. https://doi.org/10.1530/rep.1.00883 DOI: https://doi.org/10.1530/rep.1.00883
Leong CF, Raudhawati O, Cheong SK, Sivagengei K, Noor Hamidah H. Epithelial membrane antigen (EMA) or MUC1 expression in monocytes and monoblasts. Pathology 2003; 35: 422-427. https://doi.org/10.1080/00313020310001602576 DOI: https://doi.org/10.1080/00313020310001602576
Wang J, El-Bahrawy M. Expression profile of mucins (MUC1, MUC2, MUC5AC, and MUC6) in ovarian mucinous tumours: changes in expression from benign to malignant tumours. Histopathology 2015; 66: 529-535. https://doi.org/10.1111/his.12578 DOI: https://doi.org/10.1111/his.12578
Barnd DL, Lan MS, Metzgar RS, Finn OJ. Specific, major histocompatibility complex-unrestricted recognition of tumor-associated mucins by human cytotoxic T cells. Proceedings of the National Academy of Sciences of the United States of America 1989; 86: 7159-7163. https://doi.org/10.1073/pnas.86.18.7159 DOI: https://doi.org/10.1073/pnas.86.18.7159
Agrawal B, Reddish MA, Longenecker BM. In vitro induction of MUC-1 peptide-specific type 1 T lymphocyte and cytotoxic T lymphocyte responses from healthy multiparous donors. Journal of immunology (Baltimore, Md: 1950) 1996; 157: 2089-2095.
Pecher G, Finn OJ. Induction of cellular immunity in chimpanzees to human tumor-associated antigen mucin by vaccination with MUC-1 cDNA-transfected Epstein-Barr virus-immortalized autologous B cells. Proceedings of the National Academy of Sciences of the United States of America 1996; 93: 1699-1704. https://doi.org/10.1073/pnas.93.4.1699 DOI: https://doi.org/10.1073/pnas.93.4.1699
Magarian-Blander J, Ciborowski P, Hsia S, Watkins SC, Finn OJ. Intercellular and intracellular events following the MHC-unrestricted TCR recognition of a tumor-specific peptide epitope on the epithelial antigen MUC1. Journal of immunology (Baltimore, Md: 1950) 1998; 160: 3111-3120.
Akagi J, Hodge JW, McLaughlin JP, Gritz L, Mazzara G, Kufe D, Schlom J, Kantor JA. Therapeutic antitumor response after immunization with an admixture of recombinant vaccinia viruses expressing a modified MUC1 gene and the murine T-cell costimulatory molecule B7. Journal of immunotherapy (Hagerstown, Md: 1997) 1997; 20: 38-47. https://doi.org/10.1097/00002371-199701000-00004 DOI: https://doi.org/10.1097/00002371-199701000-00004
Wachowska M, Muchowicz A, Golab J. Targeting Epigenetic Processes in Photodynamic Therapy-Induced Anticancer Immunity. Frontiers in Oncology 2015; 5 DOI: https://doi.org/10.3389/fonc.2015.00176
Kontani K, Taguchi O, Narita T, Izawa M, Hiraiwa N, Zenita K, Takeuchi T, Murai H, Miura S, Kannagi R. Modulation of MUC1 mucin as an escape mechanism of breast cancer cells from autologous cytotoxic T-lymphocytes. British Journal of Cancer 2001; 84: 1258-1264. https://doi.org/10.1054/bjoc.2000.1744 DOI: https://doi.org/10.1054/bjoc.2000.1744
Lakshminarayanan V, Supekar NT, Wei J, McCurry DB, Dueck AC, Kosiorek HE, Trivedi PP, Bradley JM, Madsen CS, Pathangey LB, Hoelzinger DB, Wolfert MA, Boons GJ, Cohen PA, Gendler SJ. MUC1 Vaccines, Comprised of Glycosylated or Non-Glycosylated Peptides or Tumor-Derived MUC1, Can Circumvent Immunoediting to Control Tumor Growth in MUC1 Transgenic Mice. PloS one 2016; 11: e0145920. DOI: https://doi.org/10.1371/journal.pone.0145920
Anandkumar A, Devaraj H. Tumour immunomodulation: mucins in resistance to initiation and maturation of immune response against tumours. Scandinavian journal of immunology 2013; 78: 1-7. https://doi.org/10.1111/sji.12019 DOI: https://doi.org/10.1111/sji.12019
Oudejans JJ, ten Berge RL, Meijer C. Immune escape mechanisms in ALCL. Journal of clinical pathology 2003; 56: 423-425. https://doi.org/10.1136/jcp.56.6.423 DOI: https://doi.org/10.1136/jcp.56.6.423
Mukherjee P, Ginardi AR, Madsen CS, Sterner CJ, Adriance MC, Tevethia MJ, Gendler SJ. Mice with Spontaneous Pancreatic Cancer Naturally Develop MUC-1-Specific CTLs That Eradicate Tumors When Adoptively Transferred. The Journal of Immunology 2000; 165: 3451-3460. https://doi.org/10.4049/jimmunol.165.6.3451 DOI: https://doi.org/10.4049/jimmunol.165.6.3451
Villalba M, Rathore MG, Lopez-Royuela N, Krzywinska E, Garaude J, Allende-Vega N. From tumor cell metabolism to tumor immune escape. The international journal of biochemistry & cell biology 2013; 45: 106-113. https://doi.org/10.1016/j.biocel.2012.04.024 DOI: https://doi.org/10.1016/j.biocel.2012.04.024
Julian J, Dharmaraj N, Carson DD. MUC1 is a substrate for gamma-secretase. Journal of cellular biochemistry 2009; 108: 802-815. https://doi.org/10.1002/jcb.22292 DOI: https://doi.org/10.1002/jcb.22292
Sanchez C, Chan R, Bajgain P, Rambally S, Palapattu G, Mims M, Rooney CM, Leen AM, Brenner MK, Vera JF. Combining T-cell immunotherapy and anti-androgen therapy for prostate cancer. Prostate cancer and prostatic diseases 2013; 16: 123-131, s121. DOI: https://doi.org/10.1038/pcan.2012.49
Roulois D, Blanquart C, Panterne C, Gueugnon F, Gregoire M, Fonteneau JF. Downregulation of MUC1 expression and its recognition by CD8(+) T cells on the surface of malignant pleural mesothelioma cells treated with HDACi. European journal of immunology 2012; 42: 783-789. https://doi.org/10.1002/eji.201141800 DOI: https://doi.org/10.1002/eji.201141800
Dorn DC, Harnack U, Pecher G. Down-regulation of the human tumor antigen mucin by gemcitabine on the pancreatic cancer cell line capan-2. Anticancer research 2004; 24: 821-825.
Adriance MC, Gendler SJ. Downregulation of Muc1 in MMTV-c-Neu tumors. Oncogene 2004; 23: 697-705. https://doi.org/10.1038/sj.onc.1207165 DOI: https://doi.org/10.1038/sj.onc.1207165
Raina D, Uchida Y, Kharbanda A, Rajabi H, Panchamoorthy G, Jin C, Kharbanda S, Scaltriti M, Baselga J, Kufe D. Targeting the MUC1-C oncoprotein downregulates HER2 activation and abrogates trastuzumab resistance in breast cancer cells. Oncogene 2014; 33: 3422-3431. https://doi.org/10.1038/onc.2013.308 DOI: https://doi.org/10.1038/onc.2013.308
Li Y, Yu WH, Ren J, Chen W, Huang L, Kharbanda S, Loda M, Kufe D. Heregulin targets gamma-catenin to the nucleolus by a mechanism dependent on the DF3/MUC1 oncoprotein. Molecular cancer research : MCR 2003; 1: 765-775.
Kufe DW. MUC1-C oncoprotein as a target in breast cancer: activation of signaling pathways and therapeutic approaches. Oncogene 2013; 32: 1073-1081. https://doi.org/10.1038/onc.2012.158 DOI: https://doi.org/10.1038/onc.2012.158
Jordan NV, Bardia A, Wittner BS, Benes C, Ligorio M, Zheng Y, Yu M, Sundaresan TK, Licausi JA, Desai R, O’Keefe RM, Ebright RY, Boukhali M, Sil S, Onozato ML, Iafrate AJ, Kapur R, Sgroi D, Ting DT, Toner M, Ramaswamy S, Haas W, Maheswaran S, Haber DA. HER2 expression identifies dynamic functional states within circulating breast cancer cells. Nature 2016; 537: 102-106. https://doi.org/10.1038/nature19328 DOI: https://doi.org/10.1038/nature19328
Wood KC. Two faces of circulating breast cancer cells. Science Translational Medicine 2016; 8: 356ec149-356ec149. DOI: https://doi.org/10.1126/scitranslmed.aah7023
Arteaga Carlos L, Engelman Jeffrey A. ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics. Cancer Cell 2014; 25: 282-303. https://doi.org/10.1016/j.ccr.2014.02.025 DOI: https://doi.org/10.1016/j.ccr.2014.02.025
Krawczyk N, Banys M, Neubauer H, Solomayer EF, Gall C, Hahn M, Becker S, Bachmann R, Wallwiener D, Fehm T. HER2 status on persistent disseminated tumor cells after adjuvant therapy may differ from initial HER2 status on primary tumor. Anticancer research 2009; 29: 4019-4024.
Houssami N, Macaskill P, Balleine RL, Bilous M, Pegram MD. HER2 discordance between primary breast cancer and its paired metastasis: tumor biology or test artefact? Insights through meta-analysis. Breast cancer research and treatment 2011; 129: 659-674. https://doi.org/10.1007/s10549-011-1632-x DOI: https://doi.org/10.1007/s10549-011-1632-x
Turner NH, Di Leo A. HER2 discordance between primary and metastatic breast cancer: assessing the clinical impact. Cancer treatment reviews 2013; 39: 947-957. https://doi.org/10.1016/j.ctrv.2013.05.003 DOI: https://doi.org/10.1016/j.ctrv.2013.05.003
Bidard F-C, Peeters DJ, Fehm T, Nolé F, Gisbert-Criado R, Mavroudis D, Grisanti S, Generali D, Garcia-Saenz JA, Stebbing J, Caldas C, Gazzaniga P, Manso L, Zamarchi R, de Lascoiti AF, De Mattos-Arruda L, Ignatiadis M, Lebofsky R, van Laere SJ, Meier-Stiegen F, Sandri M-T, Vidal-Martinez J, Politaki E, Consoli F, Bottini A, Diaz-Rubio E, Krell J, Dawson S-J, Raimondi C, Rutten A, Janni W, Munzone E, Carañana V, Agelaki S, Almici C, Dirix L, Solomayer E-F, Zorzino L, Johannes H, Reis-Filho JS, Pantel K, Pierga J-Y, Michiels S. Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data. The Lancet Oncology 2014; 15: 406-414. https://doi.org/10.1016/S1470-2045(14)70069-5 DOI: https://doi.org/10.1016/S1470-2045(14)70069-5
Krishnamurthy S, Bischoff F, Ann Mayer J, Wong K, Pham T, Kuerer H, Lodhi A, Bhattacharyya A, Hall C, Lucci A. Discordance in HER2 gene amplification in circulating and disseminated tumor cells in patients with operable breast cancer. Cancer medicine 2013; 2: 226-233. https://doi.org/10.1002/cam4.70 DOI: https://doi.org/10.1002/cam4.70
Jäger BAS, Finkenzeller C, Bock C, Majunke L, Jueckstock JK, Andergassen U, Neugebauer JK, Pestka A, Friedl TWP, Jeschke U, Janni W, Doisneau-Sixou SF, Rack BK. Estrogen Receptor and HER2 Status on Disseminated Tumor Cells and Primary Tumor in Patients with Early Breast Cancer. Translational Oncology 2015; 8: 509-516. https://doi.org/10.1016/j.tranon.2015.11.009 DOI: https://doi.org/10.1016/j.tranon.2015.11.009
Pusztai L, Viale G, Kelly CM, Hudis CA. Estrogen and HER-2 Receptor Discordance Between Primary Breast Cancer and Metastasis. The Oncologist 2010; 15: 1164-1168. https://doi.org/10.1634/theoncologist.2010-0059 DOI: https://doi.org/10.1634/theoncologist.2010-0059
St. Romain P, Madan R, Tawfik OW, Damjanov I, Fan F. Organotropism and prognostic marker discordance in distant metastases of breast carcinoma: fact or fiction? A clinicopathologic analysis. Human Pathology 2012; 43: 398-404. https://doi.org/10.1016/j.humpath.2011.05.009 DOI: https://doi.org/10.1016/j.humpath.2011.05.009
Sighoko D, Liu J, Hou N, Gustafson P, Huo D. Discordance in Hormone Receptor Status Among Primary, Metastatic, and Second Primary Breast Cancers: Biological Difference or Misclassification? Oncologist 2014; 19: 592-601. https://doi.org/10.1634/theoncologist.2013-0427 DOI: https://doi.org/10.1634/theoncologist.2013-0427
Hartkopf AD, Banys M, Meier-Stiegen F, Hahn M, Röhm C, Hoffmann J, Helms G, Taran FA, Wallwiener M, Walter C, Neubauer H, Wallwiener D, Fehm T. The HER2 status of disseminated tumor cells in the bone marrow of early breast cancer patients is independent from primary tumor and predicts higher risk of relapse. Breast cancer research and treatment 2013; 138: 509-517. https://doi.org/10.1007/s10549-013-2470-9 DOI: https://doi.org/10.1007/s10549-013-2470-9
Worschech A, Kmieciak M, Knutson KL, Bear HD, Szalay AA, Wang E, Marincola FM, Manjili MH. Signatures associated with rejection or recurrence in HER-2/neu-positive mammary tumors. Cancer research 2008; 68: 2436-2446. https://doi.org/10.1158/0008-5472.CAN-07-6822 DOI: https://doi.org/10.1158/0008-5472.CAN-07-6822
Manjili MH, Arnouk H, Knutson KL, Kmieciak M, Disis ML, Subjeck JR, Kazim AL. Emergence of immune escape variant of mammary tumors that has distinct proteomic profile and a reduced ability to induce "danger signals". Breast cancer research and treatment 2006; 96: 233-241. https://doi.org/10.1007/s10549-005-9044-4 DOI: https://doi.org/10.1007/s10549-005-9044-4
Kmieciak M, Morales JK, Morales J, Bolesta E, Grimes M, Manjili MH. Danger signals and nonself entity of tumor antigen are both required for eliciting effective immune responses against HER-2/neu positive mammary carcinoma: implications for vaccine design. Cancer immunology, immunotherapy : CII 2008; 57: 1391-1398. https://doi.org/10.1007/s00262-008-0475-8 DOI: https://doi.org/10.1007/s00262-008-0475-8
Marth C, Muller-Holzner E, Greiter E, Cronauer MV, Zeimet AG, Doppler W, Eibl B, Hynes NE, Daxenbichler G. Gamma-interferon reduces expression of the protooncogene c-erbB-2 in human ovarian carcinoma cells. Cancer research 1990; 50: 7037-7041.
Knutson KL, Almand B, Dang Y, Disis ML. Neu antigen-negative variants can be generated after neu-specific antibody therapy in neu transgenic mice. Cancer research 2004; 64: 1146-1151. https://doi.org/10.1158/0008-5472.CAN-03-0173 DOI: https://doi.org/10.1158/0008-5472.CAN-03-0173
Pietrantonio F, Caporale M, Morano F, Scartozzi M, Gloghini A, De Vita F, Giommoni E, Fornaro L, Aprile G, Melisi D, Berenato R, Mennitto A, Volpi CC, Laterza MM, Pusceddu V, Antonuzzo L, Vasile E, Ongaro E, Simionato F, de Braud F, Torri V, Di Bartolomeo M. HER2 loss in HER2-positive gastric or gastroesophageal cancer after trastuzumab therapy: Implication for further clinical research. Int J Cancer 2016; 139: 2859-2864. https://doi.org/10.1002/ijc.30408 DOI: https://doi.org/10.1002/ijc.30408
Woelfle U, Sauter G, Santjer S, Brakenhoff R, Pantel K. Down-regulated expression of cytokeratin 18 promotes progression of human breast cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 2004; 10: 2670-2674. https://doi.org/10.1158/1078-0432.CCR-03-0114 DOI: https://doi.org/10.1158/1078-0432.CCR-03-0114
Yin B, Zhang M, Zeng Y, Li Y, Zhang C, Song Y. Downregulation of cytokeratin 18 is associated with paclitaxelresistance and tumor aggressiveness in prostate cancer. International journal of oncology 2016; 48: 1730-1736. https://doi.org/10.3892/ijo.2016.3396 DOI: https://doi.org/10.3892/ijo.2016.3396
Mego M, Mani SA, Lee BN, Li C, Evans KW, Cohen EN, Gao H, Jackson SA, Giordano A, Hortobagyi GN, Cristofanilli M, Lucci A, Reuben JM. Expression of epithelial-mesenchymal transition-inducing transcription factors in primary breast cancer: The effect of neoadjuvant therapy. Int J Cancer 2012; 130: 808-816. https://doi.org/10.1002/ijc.26037 DOI: https://doi.org/10.1002/ijc.26037
Pantel K, Schlimok G, Angstwurm M, Weckermann D, Schmaus W, Gath H, Passlick B, Izbicki JR, Riethmuller G. Methodological analysis of immunocytochemical screening for disseminated epithelial tumor cells in bone marrow. Journal of hematotherapy 1994; 3: 165-173. https://doi.org/10.1089/scd.1.1994.3.165 DOI: https://doi.org/10.1089/scd.1.1994.3.165
Yu M, Selvaraj SK, Liang-Chu MMY, Aghajani S, Busse M, Yuan J, Lee G, Peale F, Klijn C, Bourgon R, Kaminker JS, Neve RM. A resource for cell line authentication, annotation and quality control. Nature 2015; 520: 307-311. https://doi.org/10.1038/nature14397 DOI: https://doi.org/10.1038/nature14397
Allen M, Bjerke M, Edlund H, Nelander S, Westermark B. Origin of the U87MG glioma cell line: Good news and bad news. Science Translational Medicine 2016; 8: 354re353-354re353. DOI: https://doi.org/10.1126/scitranslmed.aaf6853
