ArticleBritish journal of cancer2018
A dualistic model of primary anal canal adenocarcinoma with distinct cellular origins, etiologies, inflammatory microenvironments and mutational signatures: implications for personalised medicine.
Article in British journal of cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- PD-L1 expression in anogenital and oropharyngeal squamous cell carcinomas associated with different clinicopathological features, HPV status and prognosis: a meta-analysis.Bioscience reports · 2021Pooled it
- Anal canal neoplasms in the modern era: integrating HPV biology, LAST terminology, and evolving molecular classification.Virchows Archiv : an international journal of pathology · 2026Review
- Tissue Context Shapes Distinct Premalignant Outcomes in an HPV16 E6/E7-Mutant Pik3ca Transgenic Mouse Model.Cancer research communications · 2026Article
- Human papillomavirus-associated adenoma of the anorectum.Histopathology · 2026Article
- Retrospective and histopathological study on epithelial tumors in the rectum and anal canal of dogs.Journal of toxicologic pathology · 2026Article
- Cancer epidemiology in rare and hereditary colorectal diseases 2) anal canal cancer (cancer statistics).International journal of clinical oncology · 2026Review
- Comprehensive Genomic Profiling of Advanced Anal Adenocarcinoma in Japan.JCO precision oncology · 2026Article
- Emerging advances and future opportunities in the molecular and therapeutic landscape of anal cancer.Nature reviews. Clinical oncology · 2025Review
- RANKL blockade inhibits cancer growth through reversing the tolerogenic profile of tumor-infiltrating (plasmacytoid) dendritic cells.Journal for immunotherapy of cancer · 2025Article
- The Clinical Utility of Circulating HPV DNA Biomarker in Oropharyngeal, Cervical, Anal, and Skin HPV-Related Cancers: A Review.Pathogens (Basel, Switzerland) · 2023Review
- Fistula-Associated Anal Adenocarcinoma: A 20-Year Single-Center Experience.Annals of surgical oncology · 2023Article
- A novel ΔNp63-dependent immune mechanism improves prognosis of HPV-related head and neck cancer.Frontiers in immunology · 2023Article
- Human papillomavirus E6/E7 oncoproteins promote radiotherapy-mediated tumor suppression by globally hijacking host DNA damage repair.Theranostics · 2023Article
- Reprogramming of connexin landscape fosters fast gap junction intercellular communication in human papillomavirus-infected epithelia.Frontiers in cellular and infection microbiology · 2023Article
- A novel multifunctional anti-PD-L1-CD16a-IL15 induces potent cancer cell killing in PD-L1-positive tumour cells.Translational oncology · 2022Article
- HPV infection alters vaginal microbiome through down-regulating host mucosal innate peptides used by Lactobacilli as amino acid sources.Nature communications · 2022Article
- Extracellular HMGB1 blockade inhibits tumor growth through profoundly remodeling immune microenvironment and enhances checkpoint inhibitor-based immunotherapy.Journal for immunotherapy of cancer · 2021Article
- SMILE-like lesion in the anal canal.Autopsy & case reports · 2021Article
- Squamous Cell Carcinoma of the Anus Incidence, Mortality, and Survival Among the General Population and Persons Living With HIV in Puerto Rico, 2000-2016.JCO global oncology · 2021Article
- Treatment algorithm and prognostic factors for patients with stage I-III carcinoma of the anal canal: a 20-year multicenter study.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2021Article
Corrections and comments
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Authors and funding
24 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPrimary adenocarcinoma of the anal canal is a rare and aggressive gastrointestinal disease with unclear pathogenesis. Because of its rarity, no clear clinical practice guideline has been defined and a targeted therapeutic armamentarium has yet to be developed. The present article aimed at addressing this information gap by in-depth characterising the anal glandular neoplasms at the histologic, immunologic, genomic and epidemiologic levels.
methodsIn this multi-institutional study, we first examined the histological features displayed by each collected tumour (n = 74) and analysed their etiological relationship with human papillomavirus (HPV) infection. The intratumoural immune cell subsets (CD4, CD8, Foxp3), the expression of immune checkpoints (PD-1, PD-L1), the defect in mismatch repair proteins and the mutation analysis of multiple clinically relevant genes in the gastrointestinal cancer setting were also determined. Finally, the prognostic significance of each clinicopathological variable was assessed.
resultsPhenotypic analysis revealed two region-specific subtypes of anal canal adenocarcinoma. The significant differences in the HPV status, density of tumour-infiltrating lymphocytes, expression of immune checkpoints and mutational profile of several targetable genes further supported the separation of these latter neoplasms into two distinct entities. Importantly, anal gland/transitional-type cancers, which poorly respond to standard treatments, displayed less mutations in downstream effectors of the EGFR signalling pathway (i.e., KRAS and NRAS) and demonstrated a significantly higher expression of the immune inhibitory ligand-receptor pair PD-1/PD-L1 compared to their counterparts arising from the colorectal mucosa.
conclusionsTaken together, the findings reported in the present article reveal, for the first time, that glandular neoplasms of the anal canal arise by HPV-dependent or independent pathways. These etiological differences leads to both individual immune profiles and mutational landscapes that can be targeted for therapeutic benefits.
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