Reduced expression of caspase-8 and cleaved caspase-3 in pancreatic ductal adenocarcinoma cells

Katarzyna Jakubowska, Katarzyna Guzińska-Ustymowicz, Waldemar Famulski, Dariusz Cepowicz, Dorota Jagodzińska, Anna Pryczynicz, Katarzyna Jakubowska, Katarzyna Guzińska-Ustymowicz, Waldemar Famulski, Dariusz Cepowicz, Dorota Jagodzińska, Anna Pryczynicz

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a rare neoplasm that affects the gastrointestinal system, and is characterized by a high mortality rate. It has been demonstrated that apoptosis has a significant role in the regulation of cancer cells. Therefore, the aim of the present study was to immunohistochemically assess the expression of proteins belonging to the caspase family, namely caspase-8, pro-caspase-3 and cleaved (active) caspase-3 in pancreatic cancer. The study group consisted of 29 patients exhibiting PDAC. Protein expression was evaluated by immunohistochemical methods. The expression of caspase-8 in normal cells was negative in 17.2% of cases and positive in 82.8% of cases. All cases demonstrated pro-caspase-3 expression in normal pancreatic cells, compared with 93.1% of cancer cells. Staining for activated caspase-3 was positive in 27 normal tissue cases, compared with positivity in only 10 cancer cases. Caspase-8 expression positively correlated with cleaved caspase-3 expression in the cytoplasm of cancer cells (P<0.002). Caspase-3 expression was identified to correlate with inflammatory peritumoral infiltration (P<0.015). No correlation was observed between caspase expression and any other clinicopathological parameters. The results of the present study demonstrated aberrant initiation of cancer cell apoptosis in PDAC via a decrease in caspase-8 expression, which may lead to disorders in the activation of effector caspase-3.

Keywords: apoptosis; caspase expression; immunohistochemistry; pancreatic ductal cancer.

Figures

Figure 1.
Figure 1.
Histopathological characteristics of pancreatic cancer tissue. (A) A moderate grade of intratumoral inflammation was observed in the stroma. Magnification, ×20. (B) A high grade of desmoplasia (magnification, ×20), (C) single focus of hemorrhage (magnification, ×20), (D) weak or moderate tumor necrosis (magnification, ×40), (E) low mitotic index and apoptotic bodies (magnification, ×40) were observed in the majority of cases. Hematoxylin and eosin staining.
Figure 2.
Figure 2.
Expression of caspase-8, pro-caspase-3 and active caspase-3 in normal and cancerous pancreatic ductal cells. (A) Positive expression of caspase-8 in ductal cells was observed in the majority of cases. (B) Positive expression of pro-caspase-3 was observed in normal tissues. (C) Strong expression of cleaved caspase-3 was observed in normal cells. (D) Caspase-8 expression was negative in ~50% of cancer cell cases. (E) Positive expression of pro-caspase-3 was observed in cancerous tissues. (F) A lack of expression of cleaved caspase-3 was observed in pancreatic ductal adenocarcinoma. Immunohistochemical staining. Magnification, ×60 (A-C) and ×40 (D-F).

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