Combination immunohistochemistry for CK5/6, p63, GATA6, and HNF4a predicts clinical outcome in treatment-naïve pancreatic ductal adenocarcinoma Journal Article

   

Authors:	Shibayama, T.; Hayashi, A.; Toki, M.; Kitahama, K.; Ho, Y. J.; Kato, K.; Yamada, T.; Kawamoto, S.; Kambayashi, K.; Ochiai, K.; Gondo, K.; Okano, N.; Melchor, J. P.; Iacobuzio-Donahue, C. A.; Sakamoto, Y.; Hisamatsu, T.; Shibahara, J.
Article Title:	Combination immunohistochemistry for CK5/6, p63, GATA6, and HNF4a predicts clinical outcome in treatment-naïve pancreatic ductal adenocarcinoma
Abstract:	Although sequence-based studies show that basal-like features lead to worse prognosis and chemotherapy-resistance compared to the classical subtype in advanced pancreatic ductal adenocarcinoma (PDAC), a surrogate biomarker distinguishing between these subtypes in routine diagnostic practice remains to be identified. We aimed to evaluate the utility of immunohistochemistry (IHC) expression subtypes generated by unsupervised hierarchical clustering based on staining scores of four markers (CK5/6, p63, GATA6, HNF4a) applied to endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) materials. EUS-FNAB materials taken from 190 treatment-naïve advanced PDAC patients were analyzed, and three IHC patterns were established (Classical, Transitional, and Basal-like pattern). Basal-like pattern (high co-expression of CK5/6 and p63 with low expression of GATA6 and HNF4a) was significantly associated with squamous differentiation histology (p < 0.001) and demonstrated the worst overall survival among our cohort (p = 0.004). IHC expression subtype (Transitional, Basal vs Classical) was an independent poor prognosticator in multivariate analysis [HR 1.58 (95% CI 1.01–2.38), p = 0.047]. Furthermore, CK5/6 expression was an independent poor prognostic factor in histological glandular type PDAC [HR 2.82 (95% CI 1.31–6.08), p = 0.008]. Our results suggest that IHC expression patterns successfully predict molecular features indicative of the Basal-like subgroup in advanced PDAC. These results provide the basis for appropriate stratification for therapeutic selection and prognostic estimation of advanced PDAC in a simplified manner. © The Author(s) 2024.
Keywords:	immunohistochemistry; adult; aged; aged, 80 and over; middle aged; genetics; mortality; pancreatic neoplasms; metabolism; carcinoma, pancreatic ductal; transcription factor; pathology; tumor marker; transcription factors; pancreas tumor; tumor suppressor proteins; cytokeratin 5; cytokeratin 6; tumor suppressor protein; tp63 protein, human; surrogate biomarker; transcription factor gata 6; gata6 transcription factor; pancreatic ductal adenocarcinoma; pancreatic ductal carcinoma; gata6 protein, human; keratin-5; keratin-6; endoscopic ultrasound guided fine needle biopsy; endoscopic ultrasound-guided fine needle aspiration; very elderly; humans; prognosis; human; male; female; hepatocyte nuclear factor 4; hnf4a protein, human; biomarkers, tumor; expressional subtypes
Journal Title:	Scientific Reports
Volume:	14
ISSN:	2045-2322
Publisher:	Nature Publishing Group
Date Published:	2024-07-06
Start Page:	15598
Language:	English
DOI:	10.1038/s41598-024-65900-w
PUBMED:	38971768
PROVIDER:	scopus
PMCID:	PMC11227498
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85197724471&doi=10.1038%2fs41598-024-65900-w&partnerID=40&md5=5d84c10080a6eb9922c31d0a2ec0e060
Notes:	Article -- Source: Scopus

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