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

Abstract

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.

Neoadjuvant chemotherapy with gemcitabine‑based regimens improves the prognosis of node positive resectable pancreatic head cancer

“…It has recently been reported that anti-cancer treatments can also induce EMT in cancer cells (37)(38)(39). We reported that residual pancreatic cancer tissues resected after preoperative chemotherapy are rich in chemoresistant cancer stem-like cells (40). If this theory is correct, the effectiveness of preoperative therapy for occult metastatic lesions is moot.…”

Original paper Morphological and immunohistochemical profile of pancreatic neuroendocrine neoplasms

“…If less than 400 cells were available in the tissue section, the case was excluded from evaluation of the particular antigen expression. For a case to be considered positive, the relative amount of positive cells had to reach the cut-off value [20][21][22][23][24][25][26][27][28], as shown in Table I. To detect the microvascular density (MVD), the endothelial layer was highlighted by membranous CD34 expression.…”

“…It is also characteristic for stem-like cancer cells, representing self-renewing cells, able to promote clonogenicity, cell growth and migration, metastatic spread and resistance to chemotherapy [11,27].…”

Neoadjuvant chemotherapy for pancreatic cancer: Effects on cancer tissue and novel perspectives

“…Additionally, it has been reported that anticancer treatments may also induce EMT in cancer cells, which may serve an important role in the aggressive behavior of tumors (67)(68)(69). Furthermore, EMT is induced in pancreatic cancer cells irrespective of whether the patient receives chemotherapy, and the interaction between cancer cells and stromal cells serves a crucial role in pancreatic cancer (70).…”

“…A concept has been proposed stating that a specific subpopulation of carcinoma cells with stem cell-like properties are responsible for tumor growth, whereas other carcinoma cells do not contribute to tumor expansion (92). In our previous study, it was demonstrated that residual pancreatic cancer tissues following preoperative chemotherapy were rich in chemoresistant cancer stem cells with the marker cluster of differentiation (CD)44 (70). A number of lines of evidence suggest an association between EMT and cancer stem cell characteristics in pancreatic cancer (93).…”