Virchows Archiv

, Volume 452, Issue 5, pp 525–534 | Cite as

Mixed-type gastric carcinomas exhibit more aggressive features and indicate the histogenesis of carcinomas

  • Hua-chuan ZhengEmail author
  • Xiao-han Li
  • Takuo Hara
  • Shinji Masuda
  • Xiang-hong Yang
  • Yi-fu Guan
  • Yasuo Takano
Original Article


To investigate the pathobiological behaviors of gastric mixed-type (MT) carcinomas and gastric carcinogenesis, the clinicopathological characteristics of MT carcinomas were analyzed and compared with intestinal-type (IT) and diffuse-type (DT) carcinomas. The expression of Ki-67, caspase-3, p53, fragile histine triad (FHIT), maspin, extracellular matrix metalloproteinase inducer (EMMPRIN), vascular growth factor (VEGF), MUC-2, 4, 5AC and 6, CD44, E-cadherin, β-catenin, and phosphorylated glycogen synthase kinase 3β-ser9 (P-GSK3β-ser9) was examined on tissue microarrays using immunohistochemistry. It was found that MT carcinomas exhibited large size, deep invasion, frequent local invasion, and lymph node metastasis in comparison with IT and DT carcinomas (p < 0.05). All the markers except MUC-5AC showed higher expression in IT than DT carcinomas (p < 0.05). The expression of maspin, EMMPRIN, VEGF, MUC-4, and membrane E-cadherin was stronger in MT intestinal than diffuse component (p < 0.05). Immunoreactivities to Ki-67, EMMPRIN, and VEGF were weaker in IT carcinoma than in the MT intestinal portion (p < 0.05), while the opposite was true for CD44, MUC-2, and MUC-6 (p < 0.05). The MT diffuse component displayed a higher expression of FHIT, VEGF, and P-GSK3β-ser9 than DT carcinoma (p < 0.05). The accumulative survival rate of the IT carcinoma patients was higher than the other types (p < 0.05). The invasive depth, venous invasion, lymph node, peritoneal or liver metastasis, and Lauren's classification were independent prognostic factors for gastric carcinomas (p < 0.05). These findings suggested that MT carcinomas were also indicated to be more aggressive than IT and DT carcinomas. Significant differences were observed in the proliferation, apoptosis, angiogenesis, mucin secretion, and cell adhesion between IT and DT carcinomas, whereas only a few of these characteristics showed differences between the MT intestinal and diffuse parts, thus suggesting that both the MT components might originate from the stem cells with similar genetic traits, but follow different histogenic pathways.


Gastric carcinoma Mixed type Lauren's classification Pathobiological behaviors Carcinogenesis 



We particularly thank Tokimasa Kumada and Hideki Hatta for their technical help and Yukari Inoue for her valuable secretarial assistance. This work was partially supported by the Japanese Ministry of Education, Science, Sports and Culture, Grant-in-Aid for Scientific Research 14770072, Japanese Smoking Foundation, Shenyang Outstanding Talent Foundation, and Natural Scientific Foundation of China (30600286).

Conflict of interest statement

No conflict of interest.

Open Access

This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.


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Copyright information

© The Author(s) 2008

Authors and Affiliations

  • Hua-chuan Zheng
    • 1
    • 2
    Email author
  • Xiao-han Li
    • 2
    • 4
  • Takuo Hara
    • 3
  • Shinji Masuda
    • 3
  • Xiang-hong Yang
    • 4
  • Yi-fu Guan
    • 1
  • Yasuo Takano
    • 2
  1. 1.Department of Biochemistry and Molecular BiologyCollege of Basic Medicine, China Medical UniversityShenyangChina
  2. 2.Department of Diagnostic PathologyGraduate School of Medicine and Pharmaceutical Science, University of ToyamaToyamaJapan
  3. 3.Kouseiren Takaoka HospitalTakaokaJapan
  4. 4.Division of PathologyShengjing Hospital of China Medical UniversityShenyangChina

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