Neoadjuvant chemotherapy with gemcitabine for pancreatic cancer increases in situ expression of the apoptosis marker M30 and stem cell marker CD44

Abstract

We examined the pathological effects of preoperative neoadjuvant chemotherapy (NAC) and the expression of markers of apoptosis, epithelial-to-mesenchymal transition (EMT) and cancer stem cells in resected pancreatic cancer specimens from patients treated with gemcitabine as NAC. Immunohistochemical expression of the apoptosis marker M30, EMT marker Snail and stem cell marker CD44 in surgically resected pancreatic cancer specimens were compared between patients treated (NAC group n=13) and not treated (control group n=21) with gemcitabine. In the NAC group, the tumor specimens showed tumor cell injury; however, there was no significant reduction of serosal, retroperitoneal, perineural or vascular invasion, lymph node metastasis or tumor size. The expression frequencies of M30 and CD44 were significantly higher in the NAC group (61.5 and 53.8%) compared to the control group (9.5 and 14.3%); however, no significant difference in Snail expression was noted between the two groups (53.8 versus 42.9%). Gemcitabine induced apoptosis of pancreatic cancer cells in vivo; however, it did not reduce the tumor burden. Moreover, the residual cancer tissues were rich in chemoresistant cancer stem cells. By contrast, marked EMT of cancer cells was observed in the specimens from the groups treated and not treated with gemcitabine.

Figure 1

Immunohistochemistry for M30, a marker of apoptosis, in pancreatic cancer tissue. M30 staining was mainly found in the nuclei of the cancer cells. The expression frequency of M30 was significantly higher in the NAC group than that in the control group. NAC, neoadjuvant chemotherapy.

Figure 2

Immunohistochemistry for CD44, a cancer stem cell marker, in pancreatic cancer tissue. CD44 staining was mainly found in the cell surface and cytoplasm in a proportion of cancer cells. A significantly higher frequency of CD44 expression was observed in the NAC group than in the control group. NAC, neoadjuvant chemotherapy.

Figure 3

Immunohistochemistry for Snail, a marker of EMT, in pancreatic cancer tissue. Snail was found in the nuclei and cytoplasm of the cancer cells. There was no significant difference in the expression frequency of Snail between the NAC group and the control group. EMT, epithelial-to-mesenchymal transition; NAC, neoadjuvant chemotherapy.