Morphological and p40 immunohistochemical analysis of squamous differentiation in endoscopic ultrasound guided fine needle biopsies of pancreatic ductal adenocarcinoma

Sci Rep. 2021 Oct 28;11(1):21290. doi: 10.1038/s41598-021-00652-5.

Abstract

The basal-like molecular subtype of pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis and upregulation in TP63ΔN (p40) network. Adenosquamous histology can be observed. This study assessed immunohistochemical p40 expression in fine needle biopsy (FNB) samples with PDAC and association with cytomorphological features of squamous differentiation and clinical data. 106 EUS FNBs with PDAC were assessed for eight cytomorphological features of squamous differentiation. P40 H-score (intensity 0-3 × percentage positive nuclei) was analysed for association with morphological features, patient age, gender, operability, chemotherapy and survival. P40 H-score in 14 paired FNBs and resections was compared. P40 h-score was 1-3 in 31%, 4-30 in 16% and > 30 in 13% of FNBs. It was significantly associated with intercellular bridges, elongated cell shape, sharp cell borders, angular nuclei with homogenous chromatin (p < 0.001) and dense cytoplasm (p = 0.002). Keratinisation was not seen. Inoperable patients (n = 81) had a shorter median survival for h-score > 30 (n = 9, 1.8 months) than for h-score ≤ 30 (n = 66, 6.7 months) not quite reaching statistical significance (p = 0.08). P40 was significantly associated with squamous morphology in FNBs with PDAC. P40 H-score > 30 showed a trend towards shorter survival in inoperable patients. Squamous differentiation may be a treatment target in PDAC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor
  • Carcinoma, Pancreatic Ductal / diagnosis*
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Carcinoma, Pancreatic Ductal / mortality
  • Endoscopic Ultrasound-Guided Fine Needle Aspiration* / methods
  • Female
  • Humans
  • Immunohistochemistry* / methods
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology*
  • Prognosis
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Biomarkers, Tumor
  • TP63 protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins