Page 103 - Read Online

Page 6 of 11 Jalal et al. J Cancer Metastasis Treat 2023;9:11 https://dx.doi.org/10.20517/2394-4722.2022.122

Furthermore, when a cystic NET is suspected, for which CEA levels are often low, chromogranin A and
neuron-specific enolase measurements have evidenced some promise in determining the neuroendocrine
nature of the cyst [43,44] .

Mucins and cytokines analysis
Mucins (MUCs) are high-weight molecular glycoproteins that play an important role in the protection of
[45]
the pancreatic duct lining . Alterations in MUC glycosylation have been observed in malignant tissues.
IPMNs express MUC2, MUCA5, and MUC4, whereas ductal adenocarcinoma expresses MUC1 but lacks
[46]
MUC2 .
An exploratory study by Lee et al. found that certain markers in cystic fluid, such as granulocyte-
macrophage colony-stimulating factor (GM-CSF) and hepatocyte growth factor (HGF), were present in
significantly higher concentrations in inflammatory cysts than in BD-IPMNs .
[47]
Higher levels of interleukin L1β (IL1β) expression were associated with high-grade dysplasia or invasive
[48]
carcinoma in IPMNs. IL1β distinguished high-risk cysts from low-risk cysts . Other markers such as
transforming growth factor β-1 (TGF-beta 1) and granulocyte colony-stimulating factor (G-CSF) are found
in high concentrations in MD-IPMNs. TGF- beta 1 alone was found in MD-IPMNs but not in BD-
IPMNs .
[49]
Molecular analysis
Mini-chromosome maintenance proteins (MCM 2e7) are expressed in a higher quantity by cancerous cells
than by benign lesions. Their expression was identified in higher concentrations in pancreatic cancers and
mucinous pancreatic cysts. Mini-chromosome maintenance 5 (MCM5) has a sensitivity of 73% and
[50]
specificity of 50% in detecting cancer in pancreatic cysts .
MicroRNA expression is abundant in malignant pancreatic lesions. There have been attempts to use
microRNA to stratify pancreatic lesions as malignant, premalignant, and benign [51,52] . A study that collected
pancreatic fluid from 40 patients (yielding 14 IPMNs, 10 mucinous, 11 serous cystadenomas, and 5 benign
cysts) found that miR-21, miR-221, and miR-17-3p were highly expressed in mucinous compared to non-
[53]
mucinous cysts (P < 0.01). MiR-21 was found to have a specificity of 76% and a sensitivity of 80% .

Several miRNA panels were found to differentiate between benign and malignant cysts . The SCA panel
[54]
contained the following miRNAs: miR-31-5p, miR-483-5p, miR-99a-5p, and miR-375. It differentiated SCA
from mucinous and pancreatic duct adenocarcinoma with 90% sensitivity and 100% specificity. The MCNs
panel consisted of the following miRNAs: miR-10b 5p, miR-202-3p, miR-210, and miR-375. Its sensitivity
and specificity were both 100%. The pancreatic duct adenocarcinoma panel contained miR-21-5p,
miR-485-3p, miR-708-5p, and miR-375 and it had a sensitivity of 95% and a specificity of 85% .
[54]

Global RNA gene expression profiling found that the neoplastic epithelium of mucinous cysts had 6.6 times
more cathepsin E (CTSE) than a normal pancreatic ductal epithelium. This finding suggests that CTSE
activity may be superior to other standard markers like CEA in identifying mucinous and malignant
pancreatic cysts .
[55]
DNA analysis
DNA testing has emerged as a new adjunct tool in the assessment of PCLs. In a study of 11 malignant, 15
premalignant, and 10 benign cysts, K-Ras-2 mutation followed by an analysis of the loss of heterozygosity