Expression of chosen cell cycle and proliferation markers in pancreatic intraepithelial neoplasia

Abstract

IntroductionPancreatic ductal adenocarcinoma is one of the most aggressive tumours that develops from precursor lesions, most frequently including pancreatic intraepithelial neoplasia (PanIN). Deregulation of the cell cycle, responsible for uncontrolled cell proliferation, is an important phenomenon in the development of this cancer.AimTo evaluate the cell cycle and the expression of proliferation markers, namely Ki67, PCNA, and cyclin D1 in pancreatic intraepithelial neoplasia at its different stages of progression.Material and methodsThe study group consisted of 70 patients with different pancreatic diseases (pancreatic ductal adenocarcinoma, pancreatitis, and pancreatic cysts), who also had pancreatic intraepithelial neoplasia. Expression of Ki67, PCNA, and Cyclin D1 was analysed immunohistochemically using appropriate antibodies.ResultsStatistically significant differences were demonstrated in Ki67, PCNA, and Cyclin D1 expression between normal pancreatic ducts and various stages of PanIN (p < 0.001). Expression of these proteins increased from normal pancreas to PanIN 1, 2, and 3. Expression of these proteins was higher in stages PanIN 1, 2, and 3 compared to normal pancreas. The expression of Ki67, PCNA, and cyclin D1 was associated with age (p < 0.001), Ki67 and PCNA with sex (p < 0.001), and PCNA with the type of primary disease (p = 0.031). Simultaneously, a directly proportional relationship was established between the expression of all proteins examined (p < 0.001).ConclusionsAn increase in the expression of Ki67, PCNA, and cyclin D1 suggests that these proteins may enhance epithelial cell proliferation and may influence the development of pancreatic intraepithelial neoplasia. Moreover, immunohistochemical assessment of Ki67, PCNA, and cyclin D1 expression may be helpful in the differential diagnosis of PanIN.

κB-Ras and Ral GTPases regulate acinar to ductal metaplasia during pancreatic adenocarcinoma development and pancreatitis

“…4a, b ). However, this might reflect the differential tumour progression in 1SKO/R and pDKO/R animals as positive Ki67 staining has been shown to increase with lesion grade 37 , 38 . To identify molecular alterations in primary ductal tumour cells, we first examined the activation status of NF-κB and Ral signalling via fluorescence-activated cell sorting (FACS) staining for phospho-NF-κB/p65 or phospho-TBK1 (TANK-binding kinase-1) as readouts for the respective pathways.…”

Ubiquitin specific peptidase 19 is a prognostic biomarker and affect the proliferation and migration of clear cell renal cell carcinoma

“…3D). Previous reports indicated that cyclin D1 and PCNA are involved in cell cycle control (21) and that p27 is a cyclin-dependent kinase inhibitor (22); these genes are thus markers of cell proliferation. Thus, mRNA levels of PCNA, cyclin D1, and p27 were evaluated via RT-qPCR.…”

Dual-Tracer Assessment of Dynamic Changes in Reoxygenation and Proliferation Decrease During Fractionated Radiotherapy in Murine Tumors

“…In a study by Chen et al elevated CAIX amounts were shown to promote tumor progression ( 34 ). Furthermore, the proliferation antigen Ki67 is closely associated with cell mitosis, playing a vital role in the initiation of cell proliferation ( 35 ). Proliferating cell nuclear antigen (PCNA) is an important trigger of multiple events in DNA replication, repair and recombination in eukaryotes and archaea, thus regulating cell proliferation ( 36 ).…”