Morphomolecular correlates of histomorphologic parameters in intrahepatic cholangiocarcinoma: A Reappraisal of the TCGA Cohort
38th European Congress of Pathology, Stockholm, İsveç, 12 - 16 Eylül 2026, ss.273, (Özet Bildiri)
- Yayın Türü: Bildiri / Özet Bildiri
- Basıldığı Şehir: Stockholm
- Basıldığı Ülke: İsveç
- Sayfa Sayıları: ss.273
- Dokuz Eylül Üniversitesi Adresli: Evet
Özet
Background & Objectives: Intrahepatic cholangiocarcinoma (ICC) is a heterogeneous malignancy with distinct histologic and molecular subtypes. While
standard CAP protocol provides a standardized framework, additional morphologic parameters may better reflect underlying tumor biology. We aimed to
reassess ICC cases from the TCGA Firehose Legacy cohort using extended morphologic features to explore their potential for prediction of morphomolecular
stratification.
Methods: ICC cases from the TCGA cohort with available histopathologic material were included. genomic and clinical data were accessed via the cBioPortal
for Cancer Genomics. Slides were reviewed for ductal subtype, growth pattern, stromal characteristics, necrosis, glandular integrity, inflammatory response,
mucin production, and intratumoral heterogeneity. Parameters were scored and statistical differences among groups were analized for genetic data.
Categorical variables were compared using Fisher’s exact or Fisher-Freeman-Halton tests, and continuous variables using Mann-Whitney U or Kruskal-Wallis
tests (p<0.05 was significant).
Results: Significant differences were identified between small duct, large duct, and mixed tumors regarding histologic grade (p=0.047), mucin production
(p=0.003), and tumor heterogeneity (p<0.001). Mucin production and high-grade morphology were more frequent in large duct/mixed tumors, while rare in
small duct tumors.
Preliminary transcriptomic analysis suggested biologically relevant differences, higher expression of ATAD3C and A1BG-AS1 in the small duct group. PREX1
protein expression was found to be significantly higher in the small duct group. Tumors with high and low peritumoral neutrophilic infiltrate differed
significantly in 115 mRNA expressions. Tumors with 3(+) tumor-infiltrating lymphocytes showed statistically significant differences in ALLC and ZNF569
mutations. The glandular integrity status showed significant differences in the AP1AR, CPSF6, PLEKHG5, HOXB3 and SAMD13 genes.
Conclusion: Ductal subtype-based classification captures critical biological variations in ICC. By incorporating additional morphologic parameters, we
detected mRNA expression and mutational differences between groups, which may lead to further research and pathologic stratification. Specifically, PREX1
emerged as a potential candidate for future tissue-level validation via immunohistochemistry.