The expression of CDX-2 and p53 immunohistochemical markers — a useful diagnostic tool for glandular dysplasia in Barrett’s oesophagus
, 1, 2, 3, 4, 1
Abstract
Introduction. Barret’s esophagus (BE), is a common state, concerning roughly about 15% of GERD patients. The pathomechanism of BE is replacement of typical squamous-cell mucosa by a layer of intestinal-type glandular mucosa (intestinal metaplasia). In a number of cases the glands are prone to dysplasia which may lead to the occurrence of esophageal adenocarcinoma. The golden standard in diagnosis of BE is endoscopy combined with histopathological examination of biopsy material of the altered Z line. Unfortunately, many guidelines do not recommend endoscopic treatment in most cases of BE in favor of long-term screening, reserving the need for treatment for dysplastic BE.
Material and methods. 53 patients suspected of BE (study group) and 45 patients without any macroscopic signs of BE (control group) underwent upper GI endoscopy during which several biopsies were taken from the elevated Z line. The study group was divided into 2 subgroups: I — without histopathological evidence of BE (n = 11); II — histopathologically confirmed BE (n = 42). In addition to the standard histopathological examination, the material was screened for levels of CDX2 and p53 expression.
Results. In the control group, none of the patients presented elevated CDX2 or p53 expression (0%). In the study group, 24 patients were CDX2 positive (45.28%) and 27 were p53 positive (50.94%). Both markers were positive in 21 cases (39.62%).
Conclusions. Standard histopathological examination combined with immunohistochemical examination can prove to be a useful tool in confirming the diagnosis of BE, diagnosing early glandular displasia and, in some cases, eliminating false negative results.
Keywords: Barrett’s oesophagusoesophageal adenocarcinomap53CDX-2
References
- Whiteman DC, Kendall BJ. Barrett's oesophagus: epidemiology, diagnosis and clinical management. Med J Aust. 2016; 205(7): 317–324.
- Spechler SJ, Souza RF. Barrett's esophagus. N Engl J Med. 2002; 346(11).
- BARRETT NR. The lower esophagus lined by columnar epithelium. Surgery. 1957; 41(6): 881–894.
- ALLISON PR. Peptic ulcer of the oesophagus. Thorax. 1948; 3(1): 20–42.
- Gajewski P, Szczeklik A. Interna Szczeklika. Medycyna Praktyczna, Gdańsk 2017: 949–957.
- Ronkainen J, Aro P, Storskrubb T, et al. Prevalence of Barrett's esophagus in the general population: an endoscopic study. Gastroenterology. 2005; 129(6): 1825–1831.
- Zajac P, Holbrook A, Super M, et al. An overview: Current clinical guidelines for the evaluation, diagnosis, treatment, and management of dyspepsia. Osteopathic Family Physician. 2013; 5(2): 79–85.
- Kahrilas P. Gastroesophageal Reflux Disease. N Engl J Med. 2008; 359(16): 1700–1707.
- Weusten B, Bisschops R, Coron E, et al. Endoscopic management of Barrett's esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement. Endoscopy. 2017; 49(2): 191–198.
- Odze RD. Diagnosis and grading of dysplasia in Barrett's oesophagus. J Clin Pathol. 2006; 59(10): 1029–1038.
- Schlemper RJ. The Vienna classification of gastrointestinal epithelial neoplasia. Gut. 2000; 47(2): 251–255.
- Anand O, Wani S, Sharma P. When and how to grade Barrett's columnar metaplasia: the Prague system. Best Pract Res Clin Gastroenterol. 2008; 22(4): 661–669.
- Lee SW, Lien HC, Chang CS, et al. Benefits of the Seattle biopsy protocol in the diagnosis of Barrett's esophagus in a Chinese population. World J Clin Cases. 2018; 6(14): 753–758.
- Fitzgerald RC, di Pietro M, Ragunath K, et al. British Society of Gastroenterology. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus. Gut. 2014; 63(1): 7–42.
- Fleischer DE, Overholt BF, Sharma VK, et al. Endoscopic radiofrequency ablation for Barrett's esophagus: 5-year outcomes from a prospective multicenter trial. Endoscopy. 2010; 42(10): 781–789.
- Sharma P, Katzka DA, Gupta N, et al. Radiofrequency ablation in Barrett's esophagus with dysplasia. N Engl J Med. 2009; 360(22): 2277–2288.
- Werling RW, Yaziji H, Bacchi CE, et al. CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: an immunohistochemical survey of 476 primary and metastatic carcinomas. Am J Surg Pathol. 2003; 27(3): 303–310.
- Krasinskas A, Goldsmith J. Immunohistology of the Gastrointestinal Tract. Diagnostic Immunohistochemistry. 2011: 500–540.
- Correa P, Piazuelo MB, Wilson KT. Pathology of gastric intestinal metaplasia: clinical implications. Am J Gastroenterol. 2010; 105(3): 493–498.
- Drewa G, Ferenc T. Genetyka medyczna. Podręcznik dla studentów. Elsevier Urban & Partner, Wrocław 2011: 148, 152.
- Boyd MT, Vlatkovic N. p53: a molecular marker for the detection of cancer. Expert Opin Med Diagn. 2008; 2(9): 1013–1024.
- Tysarowski A, Szumera-Ciećkiewicz A, Marszałek A, et al. Molecular diagnostics of cancers – practical approach. Nowotwory. Journal of Oncology. 2023; 73(3): 174–186.
- Lam AK. Introduction: Esophageal Adenocarcinoma: Updates of Current Status. Methods Mol Biol. 2018; 1756: 1–6.
- Lagergren J, Lagergren P. Recent developments in esophageal adenocarcinoma. CA Cancer J Clin. 2013; 63(4): 232–248.
- Doorakkers E, Brusselaers N. Why oesophageal adenocarcinoma is occurring more frequently. Ned Tijdschr Geneeskd. 2015; 159: A8915.
- Kula Z, Nowicki A, Świerszczyńska A. Barrett's esophagus and gland cancer - the experience of one center. Polish Journal of Surgery. 2018; 90(3): 19–24.
- Hvid-Jensen F, Pedersen L, Drewes AM, et al. Incidence of adenocarcinoma among patients with Barrett's esophagus. N Engl J Med. 2011; 365(15): 1375–1383.
- Holmberg D, Ness-Jensen E, Mattsson F, et al. Risk of oesophageal adenocarcinoma in individuals with Barrett's oesophagus. Eur J Cancer. 2017; 75: 41–46.
- Solaymani-Dodaran M, Logan RFA, West J, et al. Risk of oesophageal cancer in Barrett's oesophagus and gastro-oesophageal reflux. Gut. 2004; 53(8): 1070–1074.
- Corley D, Levin T, Habel L, et al. Surveillance and survival in Barrett's adenocarcinomas: A population-based study. Gastroenterology. 2002; 122(3): 633–640.
- Katzka DA, Fitzgerald RC. Time to Challenge Current Strategies for Detection of Barrett's Esophagus and Esophageal Adenocarcinoma. Dig Dis Sci. 2020; 65(1): 18–21.
- Didkowska J, Barańska K, Miklewska M, et al. Cancer incidence and mortality in Poland in 2023. Nowotwory. Journal of Oncology. 2024; 74(2): 75–93.