CDX2 Overexpression in Barrett’s Esophagus and Esophageal Adenocarcinoma


Background: Patients with Barrett’s esophagus have an increased risk of developing esophageal adenocarcinoma. Our purpose was to determine CDX2 expression in esophageal mucosa and establish a correlation between this marker and the progression of disease. Methods: We analyzed biopsies and surgical specimens from 150 patients who were divided into five groups according to histopathological diagnosis: G1, normal mucosa (n = 29); G2, esophagitis (n = 19); G3, columnar epithelium without intestinal metaplasia (n = 26); G4, Barrett’s esophagus (n = 32), and G5, adenocarcinoma (n = 44). Immuno-histochemical determination of CDX2 expression was considered positive in the presence of nuclear staining. Results: No CDX2 expression was detected in the G1 or G3 groups; 5% of G2, 62.5% of G4 and 70.5% of G5 patients were CDX2 positive. There was a statistically significant difference between the G4 and G5 groups compared to the G1, G2 and G3 (p < 0.05). Conclusions: CDX2 expression was observed among patients with Barrett’s esophagus and adenocarcinoma compared to other groups. CDX2 was not expressed in the phases preceding Barrett’s esophagus, but there was no linear correlation between CDX2 expression and metaplasia-adenocarcinoma progression.

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Streher, L. , Campos, V. , Mazzini, G. , Binato, M. , Meurer, L. , Edelweiss, M. and Gurski, R. (2014) CDX2 Overexpression in Barrett’s Esophagus and Esophageal Adenocarcinoma. Journal of Cancer Therapy, 5, 657-663. doi: 10.4236/jct.2014.57074.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Lord, R.V. (1999) Norman Barrett, “Doyen of Esophageal Surgery”. Annals of Surgery, 229, 428-439.
[2] DeMeester, S.R. and DeMeester, T.R. (2000) Columnar Mucosa and Intestinal Metaplasia of the Esophagus: Fifty Years of Controversy. Annals of Surgery, 231, 303-321.
[3] Caygill, C.P., Watson, A., Lao-Sirieix, P. and Fitzgerald, R.C. (2004) Barrett’s Oesophagus and Adenocarcinoma. World Journal of Surgical Oncology, 7, 12.
[4] Sampliner, R.E. (2002) Updated Guidelines for the Diagnosis, Surveillance, and Therapy of Barrett’s Esophagus. American Journal of Gastroenterology, 97, 1888-1895.
[5] Sampliner, R.E. (1998) Practice Guidelines on the Diagnosis, Surveillance, and Therapy of Barrett’s Esophagus. The Practice Parameters Committee of the American College of Gastroenterology. American Journal of Gastroenterology, 93, 1028-1032.
[6] Conio, M., Lapertosa, G., Blanchi, S. and Filiberti, R. (2003) Barrett’s Esophagus: An Update. Critical Reviews in Oncology/Hematology, 46, 187-206.
[7] Jenkins, G.J., Doak, S.H., Parry, J.M., D’Souza, F.R., Griffiths, A.P. and Baxter, J.N. (2002) Genetic Pathways Involved in the Progression of Barrett’s Metaplasia to Adenocarcinoma. British Journal of Surgery, 89, 824-837.
[8] Ronkainen, J., Aro, P., Storskrubb, T., Johansson, S.E., Lind, T., Bolling-Sternevald, E., Vieth, M., Stolte, M., Talley, N.J. and Agreus, L. (2005) Prevalence of Barrett’s Esophagus in the General Population: An Endoscopic Study. Gastroenterology, 129, 1825-1831.
[9] Dulai, G.S., Guha, S., Kahn, K.L., Gornbein, J. and Weinstein, W.M. (2002) Preoperative Prevalence of Barrett’s Esophagus in Esophageal Adenocarcinoma: A Systematic Review. Gastroenterology, 122, 26-33.
[10] Rodrigues, M.A.M. (2004) Barret’s Esophagus and Dysplasia: Diagnostic Criteria. Jornal Brasileiro de Patologia e Medicina Laboratorial, 40, 185-191.
[11] Schmidt, M.K., Meurer, L., Volkweis, B.S., Edelweiss, M.I., Schirmer, C.C., Kruel, C.D. and Gurski, R.R. (2007) c-Myc Overexpression Is Strongly Associated with Metaplasia-Dysplasia-Adenocarcinoma Sequence in the Esophagus. Diseases of the Esophagus, 20, 212-216.
[12] Phillips, R.W., Frierson Jr., H.F. and Moskaluk, C.A. (2003) Cdx2 as a Marker of Epithelial Intestinal Differentiation in the Esophagus. American Journal of Surgical Pathology, 27, 1442-1447.
[13] Steininger, H., Pfofe, D.A., Muller, H., Haag-Sunjic, G. and Fratianu, V. (2005) Expression of CDX2 and MUC2 in Barrett’s Mucosa. Pathology—Research and Practice, 201, 573-577.
[14] Eda, A., Osawa, H., Satoh, K., Yanaka, I., Kihira, K., Ishino, Y., Mutoh, H. and Sugano, K. (2003) Aberrant Expression of CDX2 in Barrett’s Epithelium and Inflammatory Esophageal Mucosa. Journal of Gastroenterology, 38, 14-22.
[15] Moskaluk, C.A., Zhang, H., Powell, S.M., Cerilli, L.A., Hampton, G.M. and Frierson Jr., H.F. (2003) Cdx2 Protein Expression in Normal and Malignant Human Tissues: An Immunohistochemical Survey Using Tissue Microarrays. Modern Pathology, 16, 913-919.
[16] Werling, R.W., Yaziji, H., Bacchi, C.E. and Gown, A.M. (2003) CDX2, a Highly Sensitive and Specific Marker of Adenocarcinomas of Intestinal Origin: An Immunohistochemical Survey of 476 Primary and Metastatic Carcinomas. American Journal of Surgical Pathology, 27, 303-310.
[17] Seno, H., Oshima, M., Taniguchi, M.A., Usami, K., Ishikawa, T.O., Chiba, T. and Taketo, M.M. (2002) CDX2 Expression in the Stomach with Intestinal Metaplasia and Intestinal-Type Cancer: Prognostic Implications. International Journal of Oncology, 21, 769-774.
[18] Bai, Y.Q., Yamamoto, H., Akiyama, Y., Tanaka, H., Takizawa, T., Koike, M., Kenji Yagi, O., Saitoh, K., Takeshita, K., Iwai, T. and Yuasa, Y. (2002) Ectopic Expression of Homeodomain Protein CDX2 in Intestinal Metaplasia and Carcinomas of the Stomach. Cancer Letters, 176, 47-55.
[19] Almeida, R., Silva, E., Santos-Silva, F., Silberg, D.G., Wang, J., De Bolos, C. and David, L. (2003) Expression of Intestine-Specific Transcription Factors, CDX1 and CDX2, in Intestinal Metaplasia and Gastric Carcinomas. Journal of Pathology, 199, 36-40.
[20] Stein, H.J., Feith, M. and Siewert, J.R. (2000) Cancer of the Esophagogastric Junction. Surgical Oncology, 9, 35-41.
[21] Levine, D.S., Blount, P.L., Rudolph, R.E. and Reid, B.J. (2000) Safety of a Systematic Endoscopic Biopsy Protocol in Patients with Barrett’s Esophagus. American Journal of Gastroenterology, 95, 1152-1157.
[22] Paull, A., Trier, J.S., Dalton, M.D., Camp, R.C., Loeb, P. and Goyal, R.K. (1976) The Histologic Spectrum of Barrett’s Esophagus. New England Journal of Medicine, 26, 476-480.
[23] Groisman, G.M., Amar, M. and Meir, A. (2004) Expression of the Intestinal Marker Cdx2 in the Columnar-Lined Esophagus with and without Intestinal (Barrett’s) Metaplasia. Modern Pathology, 17, 1282-1288.
[24] Saporiti, M.R., Almada e Souza, R.C., Pisani, J.C., Amarante, H.M., Carmes, E.R. and Sakamoto, D.G. (2003) Methylene Blue Chromoendoscopy for Barrett’s Esophagus Diagnosis. Arquivos de Gastroenterologia, 40, 139-147.
[25] Vallbohmer, D., Demeester, S.R., Peters, J.H., Oh, D.S., Kuramochi, H., Shimizu, D., Hagen, J.A., Danenberg, K.D., Danenberg, P.V., DeMeester, T.R. and Chandrasoma, P.T. (2006) Cdx-2 Expression in Squamous and Metaplastic Columnar Epithelia of the Esophagus. Diseases of the Esophagus, 19, 260-266.
[26] Jo, H.J., Lee, H.S., Kim, N., Nam, R.H., Chang, H., Kim, M.S., Kim, S.E., Oh, J.C., Lee, D.H. and Jung, H.C. (2013) Predictable Marker for Regression of Barrett’s Esophagus by Proton Pump Inhibitor Treatment in Korea. Journal of Neurogastroenterology and Motillity, 19, 210-218.

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