Strategic Role of Immunohistochemical Staining in Detection of Helicobacter pylori

Article information

Korean J Helicobacter Up Gastrointest Res. 2024;24(1):3-4
Publication date (electronic) : 2024 March 8
doi :
Division of Gastroenterology, Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
Corresponding author Hyun Ho Choi, MD, PhD Division of Gastroenterology, Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 271 Cheonbo-ro, Uijeongbu 11765, Korea E-mail:
Received 2024 January 15; Revised 2024 February 1; Accepted 2024 February 2.

Helicobacter pylori infection affects more than half of the global population and is linked to chronic gastritis, peptic ulcers, mucosa-associated lymphoid tissue lymphoma, and gastric adenocarcinoma [1].The diagnosis of H. pylori infection is crucial in treating various gastrointestinal diseases. Diagnostic methods are classified as either invasive or noninvasive, and each has limitations based on the clinical situation and laboratory setting. During endoscopic procedures, common methods for detecting H. pylori include invasive tests such as the rapid urease test or histological analysis [2]. Histology, which is often incorporated into H. pylori detection, can be enhanced by combining specific stains such as Giemsa with hematoxylin–eosin staining for increased accuracy. Histologic examination of H. pylori, along with the subsequent histologic diagnosis, is preferred when incorporating histochemical staining [3-5]. However, the reliability of histochemical tests for H. pylori may vary based on factors such as the bacterial distribution, instrument quality, and pathologist expertise. To improve the accuracy of H. pylori detection, biopsies should ideally be taken from both the antrum and body of the stomach. When only one site is biopsied, areas with minimal atrophic gastritis or intestinal metaplasia should be selected [4,6].

Immunohistochemistry (IHC) is highly effective for distinguishing H. pylori from other bacteria, especially in cases of low bacterial counts or when coccoid bacteria are present [3,7-9]. This is particularly important for patients taking proton pump inhibitors, which can induce H. pylori to change into coccoid forms and move deeper into the gastric foveolae. In complex cases requiring a definitive diagnosis, IHC staining proves crucial. Additionally, when histochemical methods fail to detect H. pylori in patients with chronic gastritis, IHC staining serves as an important ancillary test. It not only accelerates the detection process in low-density bacterial environments but also shows less variability in the interpretation of results compared with histochemical stains. Hence, IHC staining is particularly recommended in patients with chronic gastritis, in patients with atrophic gastritis with extensive intestinal metaplasia, and during post-eradication treatment follow-up when histochemical staining does not reveal the bacteria [10].

In this issue of the Korean Journal of Helicobacter and Upper Gastrointestinal Research, Hall et al. [11] compared the effectiveness of IHC stains and histochemical stains such as cresyl violet (CV) in diagnosing H. pylori from gastric biopsies. They found that IHC staining had higher sensitivity and specificity (85.2% and 97.7%, respectively) than CV (64.5% and 90.6%, respectively). IHC staining proved particularly efficient in detecting low H. pylori loads and inactive gastritis. Notably, in 14 cases, H. pylori was missed in CV-stained samples but detected in IHC-stained samples. Of these 14 cases, 12 had a low H. pylori load and 2 exhibited coccoid bacteria. The study also revealed the time-saving benefit of IHC staining, with average detection times being significantly shorter than those of CV staining.

The author recommends the use of IHC staining as a primary or confirmatory test for H. pylori, especially in complex cases. IHC staining, despite its higher cost, provides significant advantages over traditional staining methods. It is more reliable in detecting H. pylori in challenging cases such as patients with low bacterial loads or inactive gastritis. According to the current guidelines, however, histochemical staining remains the standard method for assessing H. pylori gastritis [2,3]. IHC staining is recommended as an additional test in specific cases, such as patients with chronic active gastritis in whom H. pylori is not detected through histochemistry. Importantly, IHC staining is generally not advised in cases of normal histology. Instead, IHC staining serves as a supplementary diagnostic tool, particularly when standard histochemical methods are insufficient. Additionally, in clinical practice, factors such as cost, availability, and the need for specialized laboratory equipment and expertise cannot be overlooked. The choice of a diagnostic method often depends on an appropriate balance among these factors.

This study revealed the effectiveness of IHC staining in diagnosing H. pylori, particularly in detecting low bacterial loads, inactive gastritis, and coccoid forms of the bacterium. IHC staining is best suited for specific cases in which its diagnostic superiority is crucial and when noninvasive tests or traditional stains yield inconclusive results. However, the practicality of its widespread use is challenged by high costs and equipment requirements. Therefore, the application of IHC staining should be tailored to cases in which its diagnostic superiority justifies the additional expense and resource requirements.


Availability of Data and Material

Data sharing not applicable to this article as no datasets were generated or analyzed during the study.

Conflicts of Interest

The author has no financial conflicts of interest.

Funding Statement





1. Lee YC, Chiang TH, Chou CK, et al. Association between Helicobacter pylori eradication and gastric cancer incidence: a systematic review and meta-analysis. Gastroenterology 2016;150:1113–1124.e5.
2. Malfertheiner P, Megraud F, Rokkas T, et al. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut 2022;71:1724–1762.
3. Kato M, Ota H, Okuda M, et al. Guidelines for the management of Helicobacter pylori infection in Japan: 2016 revised edition. Helicobacter 2019;24e12597.
4. Ji YH, Shi YM, Hei QW, et al. Evaluation of guidelines for diagnosis and treatment of Helicobacter pylori infection. Helicobacter 2023;28e12937.
5. Hartman DJ, Owens SR. Are routine ancillary stains required to diagnose Helicobacter infection in gastric biopsy specimens? An institutional quality assurance review. Am J Clin Pathol 2012;137:255–260.
6. Kim SG, Jung HK, Lee HL, et al. Guidelines for the diagnosis and treatment of Helicobacter pylori infection in Korea, 2013 revised edition. Korean J Gastroenterol 2013;62:3–26.
7. Malfertheiner P, Megraud F, O’Morain CA, et al. Management of Helicobacter pylori infection-the Maastricht V/Florence consensus report. Gut 2017;66:6–30.
8. Wang XI, Zhang S, Abreo F, Thomas J. The role of routine immunohistochemistry for Helicobacter pylori in gastric biopsy. Ann Diagn Pathol 2010;14:256–259.
9. Tajalli R, Nobakht M, Mohammadi-Barzelighi H, Agah S, Rastegar-Lari A, Sadeghipour A. The immunohistochemistry and toluidine blue roles for Helicobacter pylori detection in patients with gastritis. Iran Biomed J 2013;17:36–41.
10. Batts KP, Ketover S, Kakar S, et al. Appropriate use of special stains for identifying Helicobacter pylori: recommendations from the Rodger C. Haggitt Gastrointestinal Pathology Society. Am J Surg Pathol 2013;37:e12–e22.
11. Hall R, Bruce-Brand C, Mudini W, Aldera AP. Role of Helicobacter pylori immunohistochemistry in the histopathological assessment of inflamed endoscopic gastric biopsies. Korean J Helicobacter Up Gastrointest Res 2024;24:45–51.

Article information Continued