KRAS mutation testing on all non-malignant diagnosis of pancreatic endoscopic ultrasound-guided fine-needle aspiration biopsies improves diagnostic accuracy

Trisolini, Elena; Armellini, Elia; Paganotti, Alessia; Veggiani, Claudia; Bozzola, Cristina; Frattini, Milo; Pizio, Corinna; Mancuso, Giuseppe; Andorno, Silvano; Boldorini, Renzo

doi:10.1016/j.pathol.2016.12.348

Cited by 32 publications

(31 citation statements)

References 32 publications

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“…The incidence of KRAS mutations in DAC ranges 75%‐95% and represents the most frequent and earliest genetic alteration . Several studies have shown that the addition of molecular analyses improves the diagnostic performance of FNA‐EUS cytology, increasing sensitivity from 54% to 62% but decreasing specificity by 5% …”

Section: Introductionsupporting

confidence: 66%

“…Despite the difficulty of pancreatic cytology (reflected by the variable sensitivity—75%‐100%, but decreasing to 54%‐95% when a malignant group is considered and may even be inconclusive in up to 20% of cases), FNA‐EUS cytology is used for diagnosing and staging PAC . Tumour location and size, endoscopist's skills, the cytopathologist's experience and the lack of cytological evaluation at the time of sample collection can affect the diagnostic performance of cytology …”

Section: Introductionmentioning

confidence: 99%

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Addition of analysis of KRAS mutation or immunohistochemistry with MUC1 and carcinoembryonic antigen improves the diagnostic performance of fine needle aspiration cytology for the diagnosis of pancreatic carcinoma

et al. 2019

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Background Pancreatic adenocarcinoma (PAC) is a health problem because of high lethality, increasing incidence and the absence of an early diagnosis. Biopsy by fine needle aspiration guided by endoscopic ultrasound has allowed obtaining tissue for cytopathological analysis, but there are several problems with their interpretation. We aimed to compare the diagnostic performance of the cytopathological analysis with the addition of either an immunohistochemical (IHC) panel or the KRAS mutation for the diagnosis of PAC. Methods We evaluated 62 pancreatic lesions by fine needle aspiration guided by endoscopic ultrasound, applying an IHC panel with mucin (MUC)‐1, MUC4, carcinoembryonic antigen (CEA) and p53. All cases also had a KRAS mutation determination. Three cytopathologists blinded to clinical data and the KRAS status reviewed the cytology independently. We calculated diagnostic performances for the cytology alone, cytology+IHC and cytology+KRAS to show the best method to diagnose PAC. Results From 62 samples, 50 (80.6%) were PAC and 12 benign lesions. The cytopathological analysis correctly interpreted 26 malignant and 12 non‐neoplastic cases (sensitivity 52%, specificity 100% and diagnostic accuracy 61.3%). The KRAS mutation was present in 88% of PAC. The cytology+ KRAS mutation increased the sensitivity by 10% and the diagnostic accuracy by 8%. The sensitivity increased by 2% adding either MUC1 or CEA to the cytology, and the diagnostic accuracy by 10 or 18%, respectively. Conclusion The addition of IHC either with CEA or MUC1 improved the diagnostic performance of the cytology alone to diagnose PAC. The cytology + IHC evaluation was superior to the cytology + KRAS mutation to diagnose PAC.

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Section: Introductionsupporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Addition of analysis of KRAS mutation or immunohistochemistry with MUC1 and carcinoembryonic antigen improves the diagnostic performance of fine needle aspiration cytology for the diagnosis of pancreatic carcinoma

et al. 2019

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“…[27][28][29] KRAS G12 mutation has previously been shown to reliably distinguish malignancy from benign pathology, even in cases where cytology is inconclusive or even benign. [30,31] Based on our results, it would be interesting to test in a larger cohort, whether analysis of a combination of KRAS, TP53, SMAD4, and PIK3CA mutations would increase diagnostic accuracy. This study has several strengths.…”

Section: Discussionmentioning

confidence: 96%

DNA sequencing of cytopathologically inconclusive EUS-FNA from solid pancreatic lesions suspicious for malignancy confirms EUS diagnosis

et al. 2020

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Background and Objectives: EUS-FNA is inconclusive in up to 10%-15% of patients with solid pancreatic lesions (SPLs). We aimed to investigate whether supplementary genetic analyses with whole-exome sequencing add diagnostic value in patients with SPLs suspicious of malignancy but inconclusive EUS-FNA. Patients and Methods: Thirty-nine patients, who underwent EUS-FNA of an SPL were retrospectively included. Three groups were defined: 16 (41.0%) had suspected malignancy on EUS confirmed by cytology (malignant), 13 (33.3%) had suspected malignancy on EUS but benign cytology (inconclusive), and 10 (25.6%) had benign EUS imaging and cytology (benign). Areas with the highest epithelial cell concentrations were macro-dissected from the FNA smears from each patient, and extracted DNA was used for whole-exome sequencing by next-generation sequencing of a selected gene panel including 19 genes commonly mutated in cancer. Results: Pathogenic mutations in K-RAS, TP53, and PIK3CA differed significantly between the three groups (P < 0.001, P = 0.018, and P = 0.026, respectively). Pathogenic mutations in KRAS and TP53 were predominant in the inconclusive (54% and 31%, respectively) and malignant groups (81.3% and 50%, respectively) compared to the benign group (0%). Malignant and inconclusive diagnoses correlated strongly with poor overall survival (P < 0.001). Conclusion: Whole-exome sequencing of genes commonly mutated in pancreatic cancer may be an important adjunct in patients with SPLs suspicious for malignancy on EUS but with uncertain cytological diagnosis.

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“…Combination of cytology, and KRAS mutation, has been shown to increase sensitivity, especially in indeterminate cases. [ 70 71 72 ] Furthermore, the expression of several different biomarkers in FNA samples has been shown to correlate with survival. Itoi et al reported correlation between mRNA expression of ribonucleotide reductase subunit M2 (RRM2) and survival in 35 patients receiving gemcitabine.…”

Section: Novel Applications and Future Aspectsmentioning

confidence: 99%

EUS tissue acquisition: From A to B

Kovačević

Vilmann

2020

Endosc Ultrasound

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EUS-guided tissue acquisition (EUS-TA) has made rapid development since its introduction in the early 1990s. The technique is widely accepted and invaluable for staging and diagnosis of a variety of upper gastrointestinal and mediastinal lesions. Fine-needle aspiration (FNA) has long been the gold standard, but due to its limitations such as the inability to retain stroma and associated cellular architecture, novel biopsy needles (FNB) were designed. Overall, FNA and FNB needles perform seemingly equally in terms of diagnostic accuracy, however, the second-generation FNB needles require less passes. The third-generation FNB needles (crown-cut needle types) seem to be preferable to FNA needles as well as to the second-generation FNB needles, when larger histological specimens and preserved tissue architecture are required. EUS-TA is constantly under development, and new applications of this technique include tumor risk stratification according to its genetic profile as well as minimally invasive creation of patient-derived organoids, hallmarks of personized medicine. It remains yet to be shown, whether these applications will lead to a decisive shift from aspiration to biopsy, i.e. , from A to B.

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KRAS mutation testing on all non-malignant diagnosis of pancreatic endoscopic ultrasound-guided fine-needle aspiration biopsies improves diagnostic accuracy

Cited by 32 publications

References 32 publications

Addition of analysis of KRAS mutation or immunohistochemistry with MUC1 and carcinoembryonic antigen improves the diagnostic performance of fine needle aspiration cytology for the diagnosis of pancreatic carcinoma

Addition of analysis of KRAS mutation or immunohistochemistry with MUC1 and carcinoembryonic antigen improves the diagnostic performance of fine needle aspiration cytology for the diagnosis of pancreatic carcinoma

DNA sequencing of cytopathologically inconclusive EUS-FNA from solid pancreatic lesions suspicious for malignancy confirms EUS diagnosis

EUS tissue acquisition: From A to B

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