Skip to main content
Springer Nature Link
Log in

Re-evaluation of Histogenesis of Gastric Carcinomas: A Comparative Histopathological Study Between Helicobacter pylori-Negative and H. pylori-Positive Cases

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

We histopathologically re-evaluated the histogenesis of gastric carcinomas from comparative studies between Helicobacter pylori-positive and H. pylori-negative cases using the gastritis score from the Updated Sydney System. The incidence of H. pylori-negative gastric carcinomas was 3.11% (12/386); they are likely to develop in the fundic gland mucosa, and show a gastric phenotype by mucin immunohistochemistry. Even in cases of completely gastric and predominantly gastric phenotypes, CDX2 protein was expressed in most cases (90.9% of pT1 and 100% of pT2-3), indicating a possibility that intestinalization of carcinoma cells occurs independently of the background mucosa. Regarding the degree of gastritis of background mucosa surrounding 143 H. pylori-positive differentiated-type adenocarcinomas, the mean score ranged from 1.497 to 1.713. Our data support the hypothesis that intestinal metaplasia is not a precancerous but a paracancerous lesion, and most gastric adenocarcinomas develop in mildly to moderately atrophic mucosa with H. pylori-infection, i.e., ongoing atrophy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Lauren P (1965) The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand 64:31–49

    PubMed  CAS  Google Scholar 

  2. Nakamura K, Sugano H, Takagi K (1968) Carcinoma of the stomach in incipient phase: its histogenesis and histological appearances. Gann 59:251–258

    PubMed  CAS  Google Scholar 

  3. Jarvi O, Lauren P (1951) On the role of heterotopias of the intestinal epithelium in the pathogenesis of gastric cancer. Acta Pathol Microbiol Scand 29:26–44

    PubMed  CAS  Google Scholar 

  4. Tatematsu M, Ichinose M, Miki K, Hasegawa R, Kato T, Ito N (1990) Gastric and intestinal phenotypic expression of human stomach cancers as revealed by pepsinogen immunohistochemistry and mucin histochemistry. Acta Pathol Jpn 40:494–504

    PubMed  CAS  Google Scholar 

  5. Correa P (1988) A human model of gastric carcinogenesis. Cancer Res 48:3554–3560

    PubMed  CAS  Google Scholar 

  6. Marshall W (1984) Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 323:1311–1315. doi:10.1016/S0140-6736(84)91816-6

    Article  Google Scholar 

  7. Satoh K, Kimura K, Yoshida Y, Ota Y, Taniguchi Y, Kihira K et al (1994) Relationship between Helicobacter pylori and atrophic gastritis. Eur J Gastroenterol Hepatol 6(Suppl 1):S85–S88

    PubMed  Google Scholar 

  8. Parsonnet J, Friedman G, Vandersteen D, Chang Y, Vogelman J, Orentreich N et al (1991) Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med 325:1127–1131

    PubMed  CAS  Google Scholar 

  9. Nomura A, Stemmermann G, Chyou P, Kato I, Perez-Perez G, Blaser M (1991) Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. N Engl J Med 325:1132–1136

    PubMed  CAS  Google Scholar 

  10. Forman D, Newell D, Fullerton F, Yarnell J, Stacey A, Wald N et al (1991) Association between infection with Helicobacter pylori and risk of gastric cancer: evidence from a prospective investigation. BMJ 302:1302–1305

    Article  PubMed  CAS  Google Scholar 

  11. Asaka M, Takeda H, Sugiyama T, Kato M (1997) What role does Helicobacter pylori play in gastric cancer? Gastroenterology 113:S56–S60

    PubMed  CAS  Google Scholar 

  12. Hirahashi M, Yao T, Matsumoto T, Nishiyama K, Oya M, Iida M et al (2007) Intramucosal gastric adenocarcinoma of poorly differentiated type in the young is characterized by Helicobacter pylori infection and antral lymphoid hyperplasia. Mod Pathol 20:29–34. doi:10.1038/modpathol.3800714

    Article  PubMed  CAS  Google Scholar 

  13. Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M et al (2001) Helicobacter pylori infection and the development of gastric cancer. N Engl J Med 345:784–789. doi:10.1056/NEJMoa001999

    Article  PubMed  CAS  Google Scholar 

  14. Japanese Gastric Cancer Association (1998) Japanese classification of gastric carcinoma (2nd English ed). Gastric Cancer 1:10–24

    Article  PubMed  Google Scholar 

  15. Schlemper RJ, Riddell RH, Kato Y, Borchard F, Cooper HS, Dawsey SM et al (2000) The Vienna classification of gastrointestinal epithelial neoplasia. Gut 47:251–255. doi:10.1136/gut.47.2.251

    Article  PubMed  CAS  Google Scholar 

  16. Dixon M, Genta R, Yardley J, Correa P (1996) Classification and grading of gastritis. The updated Sydney system. International workshop on the histopathology of gastritis, Houston 1994. Am J Surg Pathol 20:1161–1181

    Article  PubMed  CAS  Google Scholar 

  17. Sasaki I, Yao T, Nawata H, Tsuneyoshi M (1999) Minute gastric carcinoma of differentiated type with special reference to the significance of intestinal metaplasia, proliferative zone, and p53 protein during tumor development. Cancer 85:1719–1729. doi :10.1002/(SICI)1097-0142(19990415)85:8≤1719::AID-CNCR11≥3.0.CO;2-V

    Article  PubMed  CAS  Google Scholar 

  18. Egashira Y, Shimoda T, Ikegami M (1999) Mucin histochemical analysis of minute gastric differentiated adenocarcinoma. Pathol Int 49:55–61. doi:10.1046/j.1440-1827.1999.00824.x

    Article  PubMed  CAS  Google Scholar 

  19. Wada R, Yamaguchi T, Tanizaki T (2005) Mucin phenotypic expression and p53 gene abnormality of gastric super-minute well-differentiated adenocarcinoma: re-evaluation with relationship between histogenesis of well-differentiated adenocarcinoma and intestinal metaplasia in distal stomach. J Carcinog 4:14. doi:10.1186/1477-3163-4-14

    Article  PubMed  CAS  Google Scholar 

  20. Tsukashita S, Kushima R, Bamba M, Sugihara H, Hattori T (2001) MUC gene expression and histogenesis of adenocarcinoma of the stomach. Int J Cancer 94:166–170. doi:10.1002/ijc.1460

    Article  PubMed  CAS  Google Scholar 

  21. Koseki K, Takizawa T, Koike M, Ito M, Nihei Z, Sugihara K (2000) Distinction of differentiated type early gastric carcinoma with gastric type mucin expression. Cancer 89:724–732. doi :10.1002/1097-0142(20000815)89:4≤724::AID-CNCR2≥3.0.CO;2-4

    Article  PubMed  CAS  Google Scholar 

  22. Shiroshita H, Watanabe H, Ajioka Y, Watanabe G, Nishikura K, Kitano S (2004) Re-evaluation of mucin phenotypes of gastric minute well-differentiated-type adenocarcinomas using a series of HGM, MUC5AC, MUC6, M-GGMC, MUC2 and CD10 stains. Pathol Int 54:311–321. doi:10.1111/j.1440-1827.2004.01625.x

    Article  PubMed  CAS  Google Scholar 

  23. Chawengsaksophak K, James R, Hammond VE, Kontgen F, Bech F (1997) Homeosis and intestinal tumours in Cdx2 mutant mice. Nature 386:84–87. doi:10.1038/386084a0

    Article  PubMed  CAS  Google Scholar 

  24. Bai Y, Yamamoto H, Akiyama Y, Tanaka H, Takizawa T, Koike M et al (2002) Ectopic expression of homeodomain protein CDX2 in intestinal metaplasia and carcinomas of the stomach. Cancer Lett 176:47–55. doi:10.1016/S0304-3835(01)00753-4

    Article  PubMed  CAS  Google Scholar 

  25. Kushima R, Jancic S, Hattori T (1993) Association between expression of sialosyl-Tn antigen and intestinalization of gastric carcinomas. Int J Cancer 55:904–908

    Article  PubMed  CAS  Google Scholar 

  26. Yamachika T, Inada K, Fujimitsu Y, Nakamura S, Yamamura Y, Kitou T et al (1997) Intestinalization of gastric signet ring cell carcinomas with progression. Virchows Arch 431:103–110. doi:10.1007/s004280050075

    Article  PubMed  CAS  Google Scholar 

  27. Sasaki A, Kitadai Y, Ito M, Tanaka S, Yoshihara M, Haruma K et al (2004) Mucin phenotype and background mucosa of intramucosal differentiated-type adenocarcinoma of the stomach. Oncology 66:379–387. doi:10.1159/000079486

    Article  PubMed  Google Scholar 

  28. Kawachi H, Takizawa T, Eishi Y, Shimizu S, Kumagai J, Funata N et al (2003) Absence of either gastric or intestinal phenotype in microscopic differentiated gastric carcinomas. J Pathol 199:436–446. doi:10.1002/path.1323

    Article  PubMed  Google Scholar 

  29. Hattori T (1986) Development of adenocarcinomas in the stomach. Cancer 57:1528–1534. doi :10.1002/1097-0142(19860415)57:8≤1528::AID-CNCR2820570815≥3.0.CO;2-3

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, Shiga, 520-2192, Japan

    Rie Kakinoki & Yoshihide Fujiyama

  2. Diagnostic Pathology, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, Shiga, 520-2192, Japan

    Ryoji Kushima & Akiko Matsubara

  3. Department of Endoscopic Medicine, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, Shiga, 520-2192, Japan

    Yasuharu Saito

  4. Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, Shiga, 520-2192, Japan

    Hidetoshi Okabe

  5. Department of Pathology, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, Shiga, 520-2192, Japan

    Takanori Hattori

Authors
  1. Rie Kakinoki
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Ryoji Kushima
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Akiko Matsubara
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Yasuharu Saito
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Hidetoshi Okabe
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Yoshihide Fujiyama
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Takanori Hattori
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to Ryoji Kushima.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kakinoki, R., Kushima, R., Matsubara, A. et al. Re-evaluation of Histogenesis of Gastric Carcinomas: A Comparative Histopathological Study Between Helicobacter pylori-Negative and H. pylori-Positive Cases. Dig Dis Sci 54, 614–620 (2009). https://doi.org/10.1007/s10620-008-0389-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-008-0389-5

Keywords