At present, some research efforts are focusing on the evaluation of a variety of tumor associated antigens (TAAs) for a better understanding of tumor biology and genetics of lung tumors. For this reason, we evaluated the tissue expression of carcinoembryonic antigen (CEA) and ior C2 (a cell surface O-linked glycoprotein carbohydrate chain TAA) in lung carcinomas, as well as its correlation with a variety of clinicopathological features. The tissue expression of CEA was evidenced in 22/43 (51.16%) lung carcinomas and it was correlated with mitotic activity, cell pleomorphism indexes, and age of patients. The expression of ior C2 was observed in 15/43 (34.88%) tumors but no correlation with the clinicopathological features mentioned above was obtained. No correlation between both CEA and ior C2 antigens expression and the overall survival (OS) of non-small-cell lung cancer patients was also observed. However, CEA-negative patients displayed higher OS rates as compared with positive ones (69.74 versus 58.26 months). Our results seem to be in agreement with the role of CEA expression in tumor cell proliferation, inhibition of cell polarizations and tissue architecture distortion. The significance of ior C2 antigen in these malignancies and it potential use in diagnosis, prognosis, and/or immunotherapy must be reevaluated. 1. Introduction Lung tumors are one of the leading causes of cancer-related mortality around the world [1]. There are two main variants of the disease, non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). However, NSCLC represents more than 80% of all lung carcinomas [2]. In patients with NSCLC, some genetic and regulatory abnormalities have been considered responsible for the tumor survival advantage. The alterations in gene expression that occur in cells during the malignant transformation usually conduce to the aberrant expression of antigens whether existing or not in normal cells. In this way, some research efforts are focusing on the evaluation of a variety of tumor associated antigens (TAAs) for a better understanding of tumor biology and genetics of lung tumors [3]. Carcinoembryonic antigen (CEA) is a glycoprotein expressed during embryonic and fetal development. It is frequently expressed on the apical surface of gastrointestinal epithelium, although it can also be found in other human epithelium, including lung tissues [4, 5]. Serum expression of CEA has been considered a sensitive and valuable tumor marker for diagnosis, prognosis, and therapy monitoring in lung cancer [6, 7]. Nevertheless, up to now, the
References
[1]
K. Kaira, N. Oriuchi, N. Sunaga, T. Ishizuka, K. Shimizu, and N. A. Yamamoto, “Systemic review of PET and biology in lung cancer,” American Journal of Translational Research, vol. 3, no. 4, pp. 383–391, 2011.
[2]
G. Giaccone and P. A. Zucali, “Src as a potential therapeutic target in non-small-cell lung cancer,” Annals of Oncology, vol. 19, no. 7, pp. 1219–1223, 2008.
[3]
E. Blanchard, “Targeted agents in non small cell lung cancer,” Cancer Therapy, vol. 6, pp. 95–102, 2008.
[4]
K. Kuespert, S. Pils, and C. R. Hauck, “CEACAMs: their role in physiology and pathophysiology,” Current Opinion in Cell Biology, vol. 18, no. 5, pp. 565–571, 2006.
[5]
N. Kokkonen, I. F. Ulibarri, A. Kauppila et al., “Hypoxia upregulates carcinoembryonic antigen expression in cancer cells,” International Journal of Cancer, vol. 121, no. 11, pp. 2443–2450, 2007.
[6]
M. Okada, W. Nishio, T. Sakamoto et al., “Prognostic significance of perioperative serum carcinoembryonic antigen in non-small cell lung cancer: analysis of 1,000 consecutive resections for clinical stage I disease,” Annals of Thoracic Surgery, vol. 78, no. 1, pp. 216–221, 2004.
[7]
R. Molina, J. M. Auge, J. M. Escudero et al., “Mucins CA 125, CA 19.9, CA 15.3 and TAG-72.3 as tumor markers in patients with lung cancer: comparison with CYFRA 21-1, CEA, SCC and NSE,” Tumor Biology, vol. 29, no. 6, pp. 371–380, 2009.
[8]
H. Matsuguma, R. Nakahara, S. Igarashi et al., “Pathologic stage I non-small cell lung cancer with high levels of preoperative serum carcinoembryonic antigen: clinicopathologic characteristics and prognosis,” Journal of Thoracic and Cardiovascular Surgery, vol. 135, no. 1, pp. 44–49, 2008.
[9]
M. Jung, S. H. Kim, Y. J. Lee et al., “Prognostic and predictive value of carcinoembryonic antigen and cytokeratin-19 fragments levels in advanced non-small cell lung cancer patients treated with gefitinib or erlotinib,” Yonsei Medical Journal, vol. 53, no. 5, pp. 931–939, 2012.
[10]
J. Wang, Y. Ma, Z. H. Zhu, D. R. Situ, Y. Hu, and T. H. Rong, “Expression and prognostic relevance of tumor carcinoembryonic antigen in stage IB non-small cell lung cancer,” Journal of Thoracic Disease, vol. 4, no. 5, pp. 490–496, 2012.
[11]
A. M. Vazquez, B. Tormo, A. Velandia et al., “Characterization of the colorectal antigen IOR-C2,” Hybridoma, vol. 11, no. 2, pp. 245–256, 1992.
[12]
A. M. Vazquez, B. R. Tormo, M. Alfonso et al., “Characterization of ior C5 colorectal tumor associated antigen,” Inmunologia, vol. 14, no. 3, pp. 130–132, 1995.
[13]
N. Iznaga-Escobar, M. Ramos-Suzarte, A. Morales-Morales, L. Torres-Arocha, N. Rodríguez-Mesa, and R. Pérez-Rodríguez, “99mTc-labeled murine ior C5 monoclonal antibody in colorectal carcinoma patients: pharmacokinetics, biodistribution, absorbed radiation doses to normal organs and tissues and tumor localization,” Methods and Findings in Experimental and Clinical Pharmacology, vol. 26, no. 9, pp. 687–696, 2004.
[14]
N. Iznaga-Escobar, M. Ramos-Zusarte, A. Morales-Morales, G. Nú?ez-Gandolff, and R. Pérez-Rodríguez, “99mTc-ior C5: diagnostic for colorectal cancer,” Drugs of the Future, vol. 29, no. 2, pp. 127–135, 2004.
[15]
M. Ramos-Suzarte, A. P. Pintado, N. R. Mesa et al., “Diagnostic efficacy and safety of 99mTc-labeled monoclonal antibody Ior c5 in patients with colorectal and anal carcinomas: final report clinical trial phase I/II,” Cancer Biology and Therapy, vol. 6, no. 1, pp. 22–29, 2007.
[16]
M. Ramos-Suzarte, Inmunogammagrafía de Tumores de Origen Epitelial, Académica Espa?ola, 2012.
[17]
M. Ramos-Suzarte, N. Rodríguez-Mesa, and J. Perfecto-Oliva, Inmunogammagrafía con los AcM ior c5 e Ior Cea1 en Cáncer Colorrectal. Tumores Primarios, Metástasis y Recidivas, Editorial Académica, 2013.
[18]
J. V. Gavilondo, A. M. Vázquez, S. Fong, et al., “Anticuerpos monoclonales contra el antígeno carcinoembrionario en ensayos inmunohistoquímicos e inmunocitoquímicos,” Interferón Y Biotecnología, vol. 4, no. 2, pp. 143–156, 1987.
[19]
R. Blanco, C. E. Rengifo, M. Cede?o, M. Frómeta, E. Rengifo, and A. Carr, “Immunoreactivity of the 14F7 Mab (raised against N-glycolyl GM3 ganglioside) as a positive prognostic factor in non-small cell lung cancer,” Pathology Research International, vol. 2012, Article ID 235418, 12 pages, 2012.
[20]
K. Matsuoka, S. Sumitomo, N. Nakashima, D. Nakajima, and N. Misaki, “Prognostic value of carcinoembryonic antigen and CYFRA21-1 in patients with pathological stage I non-small cell lung cancer,” European Journal of Cardio-Thoracic Surgery, vol. 32, no. 3, pp. 435–439, 2007.
[21]
R. Sirisriro, V. Boonkitticharoen, P. Kraiphibul et al., “Detection of colorectal carcinoma by anti-CEA monoclonal antibody (IOR-CEA1) labeled with (99m)Tc scintigraphy,” Hepato-Gastroenterology, vol. 47, no. 32, pp. 405–413, 2000.
[22]
S. Benchimol, A. Fuks, S. Jothy, N. Beauchemin, K. Shirota, and C. P. Stanners, “Carcinoembryonic antigen, a human tumor marker, functions as an intercellular adhesion molecule,” Cell, vol. 57, no. 2, pp. 327–334, 1989.
[23]
R. A. Screaton, L. Z. Penn, and C. P. Stanners, “Carcinoembryonic antigen, a human tumor marker, cooperates with Myc and Bcl-2 in cellular transformation,” Journal of Cell Biology, vol. 137, no. 4, pp. 939–952, 1997.
[24]
C. Ordo?ez, R. A. Screaton, C. Ilantzis, and C. P. Stanners, “Human carcinoembryonic antigen functions as a general inhibitor of anoikis,” Cancer Research, vol. 60, no. 13, pp. 3419–3424, 2000.
[25]
S. Hammarstr?m, “The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues,” Seminars in Cancer Biology, vol. 9, no. 2, pp. 67–81, 1999.
[26]
C. Ilantzis, L. Demarte, R. A. Screaton, and C. P. Stanners, “Deregulated expression of the human tumor marker CEA and CEA family member CEACAM6 disrupts tissue architecture and blocks colonocyte differentiation,” Neoplasia, vol. 4, no. 2, pp. 151–163, 2002.
[27]
W. Hauck and C. P. Stanners, “Control of carcinoembryonic antigen gene family expression in a differentiating colon carcinoma cell line, Caco-2,” Cancer Research, vol. 51, no. 13, pp. 3526–3533, 1991.
[28]
B. B. Singer, I. Scheffrahn, R. Kammerer, N. Suttorp, S. Ergun, and H. Slevogt, “Deregulation of the CEACAM expression pattern causes undifferentiated cell growth in human lung adenocarcinoma cells,” PLoS ONE, vol. 5, no. 1, Article ID e8747, 2010.
[29]
A. Koumarianou, G. Fountzilas, P. Kosmidis et al., “Non small cell lung cancer in the elderly: clinico-pathologic, management and outcome characteristics in comparison to younger patients,” Journal of Chemotherapy, vol. 21, no. 5, pp. 573–583, 2009.
[30]
D. Mauri, G. Pentheroudakis, D. Bafaloukos et al., “Non-small cell lung cancer in the young: a retrospective analysis of diagnosis, management and outcome data,” Anticancer Research, vol. 26, no. 4, pp. 3175–3182, 2006.
[31]
H. Minami, M. Yoshimura, H. Matsuoka, S. Toshihiko, and N. Tsubota, “Lung cancer treated surgically in patients years of age,” Chest, vol. 120, no. 1, pp. 32–36, 2001.
[32]
M. Cede?o, C. E. Rengifo, M. Ramos-Suzarte, R. Blanco, E. Rengifo, and F. Nogales, “IOR C2: a tumor associated antigen as potential target for immunotherapy in epithelial ovarian cancer,” Acta Microscópica, vol. 22, no. 3, 2013.
[33]
M. E. Solano, A. Perera, J. F. Batista, et al., “Immunoscintigraphic diagnosis of Ovarian Cancer with Tc-99m labeled MAb ior-c5: first Clinical Results,” World Journal of Nuclear Medicine, vol. 2, pp. 30–36, 2003.