Neoadjuvant chemotherapy with gemcitabine for pancreatic cancer increases in situ expression of the apoptosis marker M30 and stem cell marker CD44.
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.
Department of Gastroenterologic Surgery Division of Cancer Medicine, Graduate School of Medicine Science, Kanazawa University, Kanazawa.
Hidehiro
H
Tajima
Tetsuo
T
Ohta
Hirohisa
H
Kitagawa
Koichi
K
Okamoto
Seisho
S
Sakai
Jun
J
Kinoshita
Isamu
I
Makino
Hiroyuki
H
Furukawa
Hironori
H
Hayashi
Keishi
K
Nakamura
Katsunobu
K
Oyama
Masafumi
M
Inokuchi
Hisatoshi
H
Nakagawara
Hideto
H
Fujita
Hiroyuki
H
Takamura
Itasu
I
Ninomiya
Sachio
S
Fushida
Takashi
T
Tani
Takashi
T
Fujimura
Seiko
S
Kitamura
Hiroko
H
Ikeda
Koichi
K
Tsuneyama