{
  "abstract": "Background The microbiome plays a critical role in the development and progression of many gastrointestinal cancers, with Helicobacter pylori (Hp) being among the first recognized carcinogenic bacteria due to its role in gastric cancer. Hp colonizes the gastrointestinal tract of about half of the world’s population, encoding multiple virulence factors that contribute to oncogenic pathways. In this study, we examined the presence of Hp in appendiceal cancer (AC), a rare malignancy comprising multiple distinct histologic subtypes. We hypothesized that Hp may be a prevalent component of the AC microbiome, associated with patient or tumor characteristics and oncologic outcome.Methods A total of 115 formalin-fixed paraffin-embedded appendiceal tissue blocks were used to construct tissue microarrays. For neoplastic cases, tissue was selected from tumor-bearing and immediately adjacent tissue within 3mm. Comparison cases of normal appendix tissue and acute appendicitis were also analyzed. Immunohistochemistry with a Hp specific probe was performed. Using QuPath, images were digitally analyzed for Hp content per unit of tissue volume. Hp density was tested for association with patient (age, sex), tumor (histologic subtype, grade, stage, disease volume, treatment history) and immunologic characteristics (CD3+ and CD8+ lymphocytes, B cells, plasma cells, M1-like and M2-like macrophages). Spearman’s correlation test was used for continuous variables, and the Kruskal-Wallis test for categorical variables. Oncologic outcomes (progression-free and overall survival) were assessed using Cox regression.Results H. pylori density was significantly elevated in tumor-associated tissue (n=89), versus normal appendiceal (n=12) and acute appendicitis (n=14) tissue (Kruskal-Wallis p=0.0001). No significant associations were found between Hp presence and baseline patient characteristics (age or sex). Among tumor characteristics, only node-negative status was associated with Hp density (p<0.05). Histologic subtype, grade, stage and treatment history were not. No variation in immune cell counts, including T and B lymphocytes or macrophages was seen on the basis of Hp density. Interestingly, Hp density was associated with decreased overall survival (p<0.001, figure 1), a finding independent of stage or grade.Conclusions In this study, we demonstrated that H. pylori is a prevalent component of the AC microbiome and tumor microenvironment and is present at much higher density in tumor tissue relative to normal appendiceal tissue or acute appendicitis. Although we did not find evidence that Hp is associated with alterations in the immune microenvironment of AC, more refined technical assays are warranted in the future, given the substantial difference observed in survival among patients with high tumor Hp content.Ethics Approval This retrospective study was carried out in accordance with the principles of the Declaration of Helsinki and was approved by the Institutional Review Board of the Allegheny Health Network (AHN) Cancer Institute (protocols 2021-255-AHNMR, 2020-258-AGH and 2022-116-AHNCI-AGH). Waiver of informed consent was granted in accordance with 2018 Common Rule (45 CFR 46), exemption category 4. All patient records and biological samples were de-identified prior to analysis to ensure confidentiality and adherence to ethical standards, and patients were not contacted during the study.Abstract 1147 Figure 1Representative images of appendicitis control and appendiceal cancer samples detecting presence of H. pylori through immunohistochemical staining. H. pylori tissue density compared by histological subtype. KCM of OS differentiating HP density",
  "authors": [
    {
      "affiliations": [
        "Allegheny Health Network, Pittsburgh, PA, USA"
      ],
      "name": "Risha Solanki"
    },
    {
      "affiliations": [
        "Allegheny Health Network, Pittsburgh, PA, USA"
      ],
      "name": "Christopher Sherry"
    },
    {
      "affiliations": [
        "Allegheny Health Network, Pittsburgh, PA, USA"
      ],
      "name": "Hyun Young Park"
    },
    {
      "affiliations": [
        "Allegheny Health Network, Pittsburgh, PA, USA",
        "Drexel University College of Medicine, Philidelphia, PA, USA"
      ],
      "name": "Jane Zheng"
    },
    {
      "affiliations": [
        "Allegheny Health Network, Pittsburgh, PA, USA"
      ],
      "name": "Neda Dadgar"
    },
    {
      "affiliations": [
        "Allegheny Health Network, Pittsburgh, PA, USA"
      ],
      "name": "Erin Grayhack"
    },
    {
      "affiliations": [
        "Allegheny Health Network, Pittsburgh, PA, USA"
      ],
      "name": "Rose J Blodgett"
    },
    {
      "affiliations": [
        "Allegheny Health Network, Pittsburgh, PA, USA"
      ],
      "name": "Ali Zaidi"
    },
    {
      "affiliations": [
        "Allegheny Health Network, Pittsburgh, PA, USA"
      ],
      "name": "Kunhong Xiao"
    },
    {
      "affiliations": [
        "Allegheny Health Network, Pittsburgh, PA, USA"
      ],
      "name": "Ashten Omstead"
    },
    {
      "affiliations": [
        "Allegheny Health Network, Pittsburgh, PA, USA"
      ],
      "name": "Albert Donnenberg"
    },
    {
      "affiliations": [
        "Allegheny Health Network, Pittsburgh, PA, USA"
      ],
      "name": "David L Bartlett"
    },
    {
      "affiliations": [
        "University of Pittsburgh, Pittsburgh, PA, USA"
      ],
      "name": "Vera Donnenberg"
    },
    {
      "affiliations": [
        "Allegheny Health Network, Pittsburgh, PA, USA"
      ],
      "name": "Patrick L Wagner"
    }
  ],
  "title": "1147 Helicobacter pylori is prevalent in appendiceal cancer and predicts survival risk",
  "uid": "80bf8bb4-1ea0-5149-bad2-311fbc86fff3"
}