The role of imunohistochimical examiination ]n diagnosis of columnar metaplasia of esophagus
Keywords:
columnar metaplasia esophagus, Barrett esophagus, esophageal adenocarcinoma, Barrett metaplasia, Barrett immunohistochemistryAbstract
Metaplasia of esophagus represents a pathology with a chronic evolution and heterogeneous nature. One of the complications that is life-threatening is malignancy. Often it is out of sight because there is no standart approach in the screening, diagnostic and treatment of this disease. In this article we aimed to assess the value of immunohistochemical examination in the process of histopathological change, including neoplasia in patients with columnar metaplasia of esophagus. During a research project there were examined 20 patients immunohistochemically with columnar metaplasia of esophagus, with 8 immunohistochemical markers (CK7, CK20, Ki 67, EMA, CDX2, p53, HER 2, AMACR). Later the data through comparison with data of the patients with adenocarcinoma of the esogastric junction that was developed on Barrett metaplasia (from other research project) made possible the analysis of predictive biomarkers for dysplasia and neoplasia changes. Our results suggest that molecular alterations of columnar metaplasia of esophagus appear earlier than cancerous turning, and even follow a number of histopathological changes that can be perceived immunohistochemically. This means that immunohistochemical biomarkers may help in forming of preventive strategies in high-risk patients group. In the study the role of immunohistochemical examination in assessment of the characteristics of dysplasia/neoplasia evolution of esophageal metaplasia is more significant for markers: p53 and Ki 67 (0,854 and 0,808 respectively, Area ROC). CDX2 proved to be a certain immunohistochemical marker of goblet cells and is directly proportional to the risk of developing caliciform cells in gastric metaplasia defining the proces of intestinalization of columnar metaplasia esophagus.
References
1. di Pietro M, Fitzgerald RC on behalf of the BSG Barrett's guidelines working group. Revised British Society of Gastroenterology recommendation on the diagnosis and management of Barrett's oesophagus with lowgrade dysplasia. BMJ Journals. Gut. 2018; 67: 392-393. https://doi.org/10.1136/gutjnl-2017-314135
2. Matsuhashi N, Sakai E, Ohata K, Ishimura N, Fujisaki J, Shimizu T, Iijima K, Koike T, Endo T, Kikuchi T, Inayoshi T, Amano Y, Furuta T, Haruma K, Kinoshita Y. Surveillance of patients with long segment Barrett's esophagus: A multicenter prospective cohort study in Japan. Journal of Gastroenterology and Hepatology. 2017; 32(2): 409-414. https://doi.org/10.1111/jgh.13491
3. Shah T, Lippman R, Kohli D, et al. Accuracy of probebased confocal laser endomicroscopy (pCLE) compared to random biopsies during endoscopic surveillance of Barrett's esophagus. Endoscopy International Open. 2018; 6(4): E414-E420. https://doi.org/10.1055/s-0043-124868
4. Paull A, Trier JS, Dalton MD, Camp RC, Loeb P, Goyal RK. The histologic spectrum of Barrett's esophagus. The New England Journal of Medicine. 1976; 295(9): 476-480. https://doi.org/10.1056/NEJM197608262950904
5. Lindblad M, Bright T, Schloithe A, Mayne GC, Chen G, Bull J, Bampton PA, Fraser RJ, Gatenby PA, Gordon LG, et al. Toward More Efficient Surveillance of Barrett's Esophagus: Identification and Exclusion of Patients at Low Risk of Cancer. World Journal of Surgery. 2017; 41(4): 1023-1034. https://doi.org/10.1007/s00268-016-3819-0
6. Ungureanu S., Istrate V., Tîrbu V., Șipitco N., Fosa D. Aspecte moderne de diagnostic și tratament al esofagului columnar metaplaziat. Arta Medica 2019; 3(72): 95.
7. Mukaisho KI, Kanai S, Kushima R, Nakayama T, Hattori T, Sugihara H. Barretts's carcinogenesis. Pathology International. 2019; 69(6): 319-330. https://doi.org/10.1111/pin.12804
8. Zhang W, Wang DH. Origins of Metaplasia in Barrett's Esophagus: Is this an Esophageal Stem or Progenitor Cell Disease? Digestive Diseases and Sciences. 2018; 63(8): 2005-2012. https://doi.org/10.1007/s10620-018-5069-5
9. di Pietro M, Boerwinkel DF, Shariff MK, et al. The combination of autofluorescence endoscopy and molecular biomarkers is a novel diagnostic tool for dysplasia in Barrett's oesophagus. BMJ Journals. Gut. 2015; 64(1): 49-56. https://doi.org/10.1136/gutjnl-2013-305975
10. Fosa D., Tratamentul chirurgical multimodal al pacienților cu metaplazie epitelială columnară de mucoasă esofagiană. Teza de doctor în șt. med., Editura: Chișinău, Anul creării: 2022, 210 p., Limba: Romînă.
11. di Pietro M, Fitzgerald RC on behalf of the BSG Barrett's guidelines working group. Revised British Society of Gastroenterology recommendation on the diagnosis and management of Barrett's oesophagus with lowgrade dysplasia. BMJ Journals. Gut. 2018; 67: 392-393 https://doi.org/10.1136/gutjnl-2017-314135
12. Wong A, Fitzgerald RC. Epidemiologic risk factors for Barrett's esophagus and associated adenocarcinoma. Clinical Gastroenterology and Hepatology. 2005; 3(1): 1-10. https://doi.org/10.1016/S1542-3565(04)00602-0
13. Falk GW. Barrett's oesophagus: frequency and prediction of dysplasia and cancer. Best Practice & Reserch Clinical Gastroenterology. 2015; 29(1): 125-38. https://doi.org/10.1016/j.bpg.2015.01.001
14. Fock KM, Talley N, Goh KL, et al. Asia-Pacific consensus on the management of gastro-oesophageal reflux disease: an update focusing on refractory reflux disease and Barrett's oesophagus. BMJ Journals. Gut. 2016; 65(9): 1402-1415. https://doi.org/10.1136/gutjnl-2016-311715
15. Thota PN, Vennalaganti P, Vennelaganti S, et al. Low risk of high-grade dysplasia or esophageal adenocarcinoma among patients with Barrett's esophagus less than 1 cm (irregular Z line) within 5 years of index endoscopy. Gastroenterology. 2017; 152(5): 987-992. https://doi.org/10.1053/j.gastro.2016.12.005
16. Bhat S, Coleman HG, Yousef F, Johnston BT, McManus DT, Gavin AT, Murray LJ. Risk of malignant progression in Barrett's esophagus patients: results from a large population-based study. Journal of the NATIONAL CANCER INSTITUTE. 2011; 103(13): 1049-1057. https://doi.org/10.1093/jnci/djr203
17. Salemme M, Villanacci V, Cengia G, Cestari R, Missale G, Bassotti G. Intestinal metaplasia in Barrett's oesophagus: An essential to predict the risk of dysplasia and cancer development. Digestive and Liver Disease. 2016; 48: 144-147. https://doi.org/10.1016/j.dld.2015.10.021
18. Ma M, Shroff S, Feldman M, DeMarshall M, Price C, Tierney A, Falk GW. Risk of malignant progression in Barrett's esophagus indefinite for dysplasia. Diseases of the Esophagus. 2017; 30(3): 1-5. https://doi.org/10.1093/dote/dow025
19. Biswas S, Quante M, Leedham S, Jansen M. The metaplastic mosaic of Barrett's oesophagus. Virchows Archiv. 2018; 472(1): 43‐54. https://doi.org/10.1007/s00428-018-2317-1
20. McDonald SA, Graham TA, Lavery DL, Wright NA, Jansen M. The Barrett's gland in phenotype space. Cellular and Molecular Gastroenterology and Hepatology. 2014; 1(1): 41‐54. https://doi.org/10.1016/j.jcmgh.2014.10.001
21. McDonald SA, Lavery D, Wright NA, Jansen M. Barrett oesophagus: lessons on its origins from the lesion itself. Nature Reviews Gastroenterology & Hepatology. 2015; 12(1): 50‐60. https://doi.org/10.1038/nrgastro.2014.181
22. Srivastava S, Liew MS, McKeon F, et al. Immunohistochemical analysis of metaplastic non‐goblet columnar lined oesophagus shows phenotypic similarities to Barrett's oesophagus: a study in an Asian population. Digestive Liver Diseas. 2014; 46(2): 170‐175. https://doi.org/10.1016/j.dld.2013.09.025
23. Lavery DL, Martinez P, Gay LJ, et al. Evolution of oesophageal adenocarcinoma from metaplastic columnar epithelium without goblet cells in Barrett's oesophagus. Gut. BMJ Journal. 2016; 65(6): 907‐913. https://doi.org/10.1136/gutjnl-2015-310748
24. Kunze B, Wein F, Fang HY, et al. Notch signaling mediates differentiation in Barrett's esophagus and promotes progression to adenocarcinoma. Gastroenterology. 2020; 159(2): 575‐590. https://doi.org/10.1053/j.gastro.2020.04.033
25. Janmaat VT, van Olphen SH, Biermann KE, Looijenga LHJ, Bruno MB, Spaander MCW. Use of immunohistochemical biomarkers as independent predictor of neoplastic progression in Barrett's oesophagus surveillance: a systematic review and meta‐analysis. PLoS One. PLOS PATHOGENS. 2017; 12(10): e0186305. https://doi.org/10.1371/journal.pone.0186305
26. Snyder P, Dunbar K, Cipher DJ, Souza RF, Spechler SJ, Konda VJA. Aberrant p53 immunostaining in Barrett's esophagus predicts neoplastic progression: systematic review and meta‐analyses. Digestive Diseas Sciens. 2019; 64(5): 1089‐1097. https://doi.org/10.1007/s10620-019-05586-7
27. Altaf K, Xiong JJ, la Iglesia D, Hickey L, Kaul A. Metaanalysis of biomarkers predicting risk of malignant progression in Barrett's oesophagus. British Journalof Surgery. 2017; 104(5): 493‐502. https://doi.org/10.1002/bjs.10484
28. Baak JP, ten Kate FJ, Offerhaus GJ, van Lanschot JJ, Meijer GA. Routine morphometrical analysis can improve reproducibility of dysplasia grade in Barrett's oesophagus surveillance biopsies. Journal of Clinical Pathology. 2002; 55(12): 910‐916. https://doi.org/10.1136/jcp.55.12.910
29. Weston AP, Banerjee SK, Sharma P, Tran TM, Richards R, Cherian R. p53 protein overexpression in low grade dysplasia (LGD) in Barrett's esophagus: immunohistochemical marker predictive of progression. American Journal of Gastroenterology. 2001; 96(5): 1355‐1362. https://doi.org/10.1111/j.1572-0241.2001.03851.x
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