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

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.

SUBMITTER: Haugk B

PROVIDER: S-EPMC8553828 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The aim of this study is to perform a cost-effectiveness comparison between palpation-guided thyroid fine-needle aspiration biopsies (P-FNA) and ultrasound-guided thyroid FNA biopsies (USG-FNA).Each nodule was considered as a case. Diagnostic steps were history and physical examination, TSH measurement, Tc99m thyroid scintigraphy for nodules with a low TSH level, initial P-FNA versus initial USG-FNA, repeat USG-FNA for nodules with initial inadequate P-FNA or USG-FNA, hemithyroidectomy for inadequate repeat USG-FNA. American Thyroid Association thyroid nodule management guidelines were simulated in estimating the cost of P-FNA strategy. American Association of Clinical Endocrinologists guidelines were simulated for USG-FNA strategy. Total costs were estimated by adding the cost of each diagnostic step to reach a diagnosis for 100 nodules. Strategy cost was found by dividing the total cost to 100. Incremental cost-effectiveness ratio (ICER) was calculated by dividing the difference between strategy cost of USG-FNA and P-FNA to the difference between accuracy of USG-FNA and P-FNA. A positive ICER indicates more and a negative ICER indicates less expense to achieve one more additional accurate diagnosis of thyroid cancer for USG-FNA.Seventy-eight P-FNAs and 190 USG-FNAs were performed between April 2003 and May 2008. There were no differences in age, gender, thyroid function, frequency of multinodular goiter, nodule location and diameter (median nodule diameter: 18.4 mm in P-FNA and 17.0 mm in USG-FNA) between groups. Cytology results in P-FNA versus USG-FNA groups were as follows: benign 49% versus 62% (p = 0.04), inadequate 42% versus 29% (p = 0.03), malignant 3% (p = 1.00) and indeterminate 6% (p = 0.78) for both. Eleven nodules from P-FNA and 18 from USG-FNA group underwent surgery. The accuracy of P-FNA was 0.64 and USG-FNA 0.72. Unit cost of P-FNA was 148 Euros and USG-FNA 226 Euros. The cost of P-FNA strategy was 534 Euros and USG-FNA strategy 523 Euros. Strategy cost includes the expense of repeat USG-FNA for initial inadequate FNAs and surgery for repeat inadequate USG-FNAs. ICER was -138 Euros.Universal application of USG-FNA for all thyroid nodules is cost-effective and saves 138 Euros per additional accurate diagnosis of benign versus malignant thyroid nodular disease.ClinicalTrials.gov, NCT00571090.

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

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