Biomarkers of gastric atrophy at stomach cancer

Background. Atrophic gastritis (AG), being the basic premalignant condition for the stomach cancer (SC), is commonly diagnosed and screened for by noninvasive biomarkers (pepsinogens, gastrin-17), however the data on those biomarkers at SC is inconsistent. Aim of investigation. To evaluate the markers of stomach atrophy along with risk factors of SC of different localization, histological type and stage in the «case series» study. Material and methods. Original investigation was designed as «case series», that included 85 patients with SC (48 m and 37 f, mean age 61.2±13,6 years) who were consistently referred to two medical institutions. All patients underwent interviewing the questionnaire concerning smoking and alcohol consumption, presence of gastroenterological symptoms and family history. Blood serum samples were analyzed using ELISA test kits «GastroPanel» («Biohit Plc», Finland). Manufacturer recommended threshold levels were used at diagnostics of AG. Results. The diagnosis of SC of the III to IV stage was established in 67.9% of patients. The most common location of the neoplasm was the stomach body (63,5%). Helicobacter pylori (H. pylori) infection was revealed by serological method in 74.1% of cases, of which in 15.1% the attempt of eradication treatment was carried out. In 90.6% of patients the adenocarcinoma of different differentiation grade was diagnosed, low degree of differentiation was the most common (57.6%). Signet-ring cell carcinoma was diagnosed in 7.1% of patients, undifferentiated tumor - in 2.4%. Pepsinogen-I (PGI) level under 50 mcg/l was found in 43.2% of patients, indicating different degrees of fundic atrophy. Significantly lower PGI scores were detected in SC patients with histologically verified atrophy. No significant differences in biomarker levels according to tumor location, histological type of SC and tumor stage were found. Conclusions. The «case series» study demonstrated high rate of late SC diagnostics with predominance of corpus location and the most malignant types. H. pylori infection was diagnosed in serologically in the most of patients, however attempts for eradication therapy was carried out only in 15% of patients. Fundic atrophy was diagnosed by serological tests in over 40% of patients, however no association with location, stage and morphological type of the tumor was established. Blood serum samples were analyzed using ELISA test kits «GastroPanel» («Biohit Plc», Finland). Manufacturer recommended threshold levels were used at diagnostics of AG.

рак желудка, атрофический гастрит, неинвазивная диагностика, пепсиногены, Helicobacter pylori

1. Schistosomes, liver flukes and Helicobacter pylori. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Lyon, 7-14 June 1994. IARC Monogr Eval Carcinog Risks Hum 1994;61:1-241.

2. Crew K.D., Neugut A.I. Epidemiology of gastric cancer. World J Gastroenterol 2006 Jan 21; 12(3):354-62.

3. Blot W.J., Devesa S.S., Kneller R.W., Fraumeni J.F. Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA 1991; 265:1287-9.

4. Brown L.M., Devesa S.S. Epidemiologic trends in esophageal and gastric cancer in the United States. Surg Oncol Clin N Am 2002; 11:235-56.

5. Raghunath A., Hungin A.P., Wooff D., Childs S. Prevalence of Helicobacter pylori in patients with gastrooesophageal reflux disease: systematic review. Br Med J 2003; 326:737.

6. Correa P. Human gastric carcinogenesis: a multistep and multifactorial process. First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res 1992 Dec15;52(24):6735-40.

7. McMichael A.J., McCall M.G., Hartshorne J.M., Woodings T.L. Patterns of gastro-intestinal cancer in European migrants to Australia: the role of dietary change. Int J Cancer 1980; 25:431-7.

8. Давыдов М.И., Аксель Е.М. Статистика злокачественных новообразований в России и странах СНГ в 2012 году. М.; 2014. 226 с.

9. Lauren P. The two histological main types of gastric carcinoma: Diffuse and so-called intestinal-type carcinoma. Anattempt at a histo-clinical classification. Acta Pathol Microbiol Scand 1965; 64:31-49.

10. Zheng H., Takahashi H. Pathobilogical characteristics of intestinal and diffuse-type gastric carcinoma in Japan: an immunostaining study on the tissue microarray. J Clin Pathol 2007; 60:273-7.

11. Agréus L., Kuipers E. .J, Kupcinskas L., Malfertheiner P. et al. Rationale in diagnosis and screening of atrophic gastritis with stomach-specific plasma biomarkers. Scand J Gastroenterol 2012; 47(2):136-47.

12. Пасечников В.Д., Чуков С.З. Предраковые изменения желудка и возможности эрадикационной терапии в профилактике Н. рylori-ассоциированного рака желудка. Рос журн гастроэнтерол гепатол колопроктол 2006; 3:52-7.

13. An international association between Helicobacter pylori infection and gastric cancer. The Eurogastt Study Group. Lancet 1993; 341:1359-62.

14. Schlemper R.J., Riddell R.H., Kato Y., Borchard F., Cooper H.S. et al. The Vienna classifcation of gastrointestinal epithelial neoplasia. Gut 2000 Aug;47(2):251-5.

15. Parsonnet J. The incidence of Helicobacter pylori infection. Aliment Pharmacol Ther 1995; 9 (Suppl 2):4551.

16. Yanaoka K., Oka M., Yoshimura N., Mukoubayashi C., Enomoto S. et al. Risk of gastric cancer in asymptomatic, middle-aged Japanese subjects based on serum pepsinogen and Helicobacter pylori antibody levels. Int J Cancer 2008;123:917-26.

17. Sanduleanu S., Jonkers D., De Bruine A., Hameeteman W., Stockbrugger R.W. Non-Helicobacter pylori bacterial flora during acid-suppressive therapy: differential findings in gastricjuice and gastric mucosa. Aliment Pharmacol Ther 2001; 15:379-88.

18. Stalnikowicz R., Benbassat J. Risk of gastric cancer after gastric surgery for benign disorders. Arch Intern Med 1990; 150:2022-6.

19. Levine P.H., Stemmermann G., Lennette E.T., Hildesheim A., Shibata D., Nomura A. Elevated antibody titers to Epstein-Barr virus prior to the diagnosis of Epstein-Barr-virus-associated gastric adenocarcinoma. Int J Cancer 1995; 60:642-4.

20. Злокачественные новообразования в России в 2016 г. (заболеваемость, смертность). Под ред. А.Д. Каприна, В.В. Страчунского, Г.В. Петровой. М.: МНИОИ им. П.А. Герцена - филиал ФГБНУ МИЦ радиологии МЗ России; 2018. 250 с.

21. Опенко Т.Г., Решетников О.В., Курилович С.А., Симонова Г.И. Рак желудка в Новосибирске на рубеже тысячелетий (тренды заболеваемости и смертности, возможности профилактики). Вопр онкол 2013; 59(6):708-13.

22. Hu P.J., Mitchell H.M., Li Y.Y., Zhou M.H., Hazell S.L. Association of Helicobacter pylori with gastric cancer and observations on the detection of this bacterium in gastric cancer cases. Am J Gastroenterol 1994; 89:1806-10.

23. Barreto-Zuniga R., Maruyama M., Kato Y., Aizu K., Ohta H., Takekoshi T., Bernal S.F. Significance of Helicobacter pylori infection as a risk factor in gastric cancer: serological and histological studies. J Gastroenterol 1997; 32:289-94.

24. Uemura N., Okamoto S., Yamamoto S., Matsumura N., Yamaguchi S., Yamakido M. et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med 2001; 345:784-9.

25. Kurilovich S., Belkovets A., Reshetnikov O., Openko T., Malyutina S., Ragino Y. et al. Stomachspecific Biomarkers (GastroPanel) Can Predict the Development of Gastric Cancer in a Caucasian Population: A Longitudinal Nested Case-Control Study in Siberia. Anticancer Res 2016 Jan; 36(1):247-53.

26. Kosunen T.U., Pukkala E., Sarna S., Seppälä K., Aromaa A., Knept P. et al. Gastric cancer in Finnish patients after cure of Helicobacter pylori infection: a cohort study. Int J Cancer 2011; 128:433-9.

27. Koizumi Y., Tsubono Y., Nakaya N., Kuriyama S., Shibuya D, Matsuoka H., Tsuji I. Cigarette smoking and the risk of gastric cancer: a pooled analysis of two prospective studies in Japan. Int J Cancer 2004; 112:104955.

28. Franceschi S., La Vecchia C. Alcohol and the risk of cancers of the stomach and colon-rectum. Dig Dis 1994; 12:276-89.

29. Parthasarathy G., Maroju N.K., Kate V., Ananthakrishnan N., Sridhar M.G. Serum pepsinogen I and II levels in various gastric disorders with special reference to their use as a screening test for carcinoma stomach. Trop Gastroenterol 2007 Oct-Dec;28(4):166-70.

30. Белковец А.В., Курилович С.А., Решетников О.В., Рагино Ю.И., Щербакова Л.В. Неинвазивная диагностика фенотипа гастрита в клинической практике: анализ первой тысячи исследований. Экспер и клин гастроэнтерол 2015; 3:26-30.

31. So J.B., Yeoh K.G., Moochala S., Chachlani N., Ho J., Wong W.K., Mack P., Goh P.M. Serum pepsinogen levels in gastric cancer patients and their relationship with Helicobacter pylori infection: a prospective study. Gastric Cancer 2002;5(4):228-32.

32. Соснина А.В., Сорокина Н.Н., Аутеншлюс А.И., Морозов Д.В. и др. Взаимосвязь уровней пепсиногенов в сыворотке крови с патогистологическими параметрами аденом и аденокарцином желудка. Клин лабор диагн 2013;2:21-3.

33. Bornschein J., Selgrad M., Wex T., Kuester D., Malfertheiner P. Serological assessment of gastric mucosal atrophy in gastric cancer. BMC Gastroenterol 2012; 12:10.

34. Белковец А.В., Курилович С.А., Решетников О.В., Рагино Ю.И., Щербакова Л.В. Распространённость и особенности фундального атрофического гастрита в популяции с высоким уровнем Helicobacter pylori инфекции. Экспер и клин гастроэнтерол 2016; 133(9):813.

35. Miki K. Gastric cancer screening using the serum pepsinogen test method. Gastric Cancer 2006; 9:245-53.