Toshihisa Ito

Expression of p27 is associated with Bax expression and spontaneous apoptosis in oral and oropharyngeal carcinoma

p27Kip1, a cyclin‐dependent kinase inhibitor, is a negative regulator of the cell cycle, and apoptosis is a genetically encoded program of cell death. To clarify the relationship between the cell cycle and apoptosis, we investigated expression of p27, cyclin D1 and apoptosis‐related proteins (p53, Bax, Bcl‐2 and c‐Myc) in 60 cases of oral and oropharyngeal squamous‐cell carcinoma (SCC) using an immuno‐histochemical approach, and evaluated spontaneous apoptosis in vivo. Our most notable finding was that spontaneous apoptosis in the p27‐positive group was significantly higher than that in the p27‐negative group (p = 0.028). In addition, the percentage of p27‐positive cells was clearly correlated with that of Bax‐positive cells (γ = 0.288, p = 0.028) and with that of cyclin D1‐positive cells (γ = 0.416, p = 0.002). Expression of p27 was inversely associated with the clinical stage of total tumor progression (p = 0.027). However, no correlation was found between p27 expression and the following parameters: gender, tumor size, lymph node metastasis, overall survival and disease‐free survival. Our results give evidence that the action of the cell‐cycle regulator p27 is closely linked with apoptosis in clinical samples from patients and indicate that over‐expression of p27 might induce apoptosis in cancer cells through elevation of Bax expression, thereby acting on tumor progression. Int. J. Cancer (Pred. Oncol.) 84:315–320, 1999.

Decreased expression of Bax is correlated with poor prognosis in oral and oropharyngeal carcinoma

We investigated the expression of apoptosis-related factors, p53, Bax, Bcl-2, and spontaneous apoptosis in 57 cases of oral and oropharyngeal squamous cell carcinoma (SCC) by immunochemical staining and ApopTag kit. Positive expression of Bax was inversely associated with advanced tumor stage (P = 0.0225), lymph node metastasis (P = 0.0225), clinical stage (P = 0.0083) and poor prognosis (P = 0.0478). Positive expression of p53 was related to poor prognosis (P = 0.0445) and was associated with negative expression of Bax (P = 0.0439). The apoptosis index did not correlate with clinical outcome. These results suggest that abnormality of Bax expression plays an important role in tumor progression in oral and oropharyngeal SCC.

Expression of Fas (CD95) ligand is correlated with IL-10 and granulocyte colony-stimulating factor expression in oral and oropharyngeal squamous cell carcinoma

The Fas/Fas ligand (FasL) pathway has been shown to be an important cellular pathway mediating apoptosis. In this study we investigated the expression of Fas and FasL and the rate of spontaneous apoptosis in 58 oral and oropharyngeal squamous cell carcinoma (SCC) by using immunohistochemical techniques. There was no correlation between Fas or FasL expression and clinicopathological factors. The expression of Fas in the tumor did not affect spontaneous apoptosis of the tumor cells. However, FasL expression was associated with IL-10 and granulocyte colony-stimulating factor expression in oral and oropharyngeal SCC. These results suggested that the Fas/FasL system is connected with the expression of various factors including cytokines in tumor cells.

Appearance of bax protein after preoperative chemoradiotherapy is a prognostic factor in maxillary cancer.

The prognosis for maxillary squamous cell carcinoma (SCC) remains poor, despite advances in combination therapy. Combined treatment with anticancer drugs and radiation therapy is aimed at inducing apoptosis. As apoptosis is regulated by several proteins, we investigated the expression of p53, Bax and Bcl-2 in maxillary SCC before treatment and after preoperative chemoradiotherapy using an immunohistochemical approach. Furthermore, apoptotic cells were visualized using an in situ apoptosis detection kit and the apoptosis index (AI) was defined as the number of positive cancer cells per 1000 cancer cells. Expression of p53 and Bcl-2 and the AI in 23 maxillary SCCs were not associated with tumor size, lymph node metastasis, clinical stage, frequency of recurrence or 5-year survival rate either before treatment or after preoperative chemoradiotherapy. Bax expression before treatment was not correlated with any clinicopathological factors before treatment. However, no patients in the Bax-positive group (11/22 cases) after preoperative chemoradiotherapy had recurrence of maxillary SCC and all were alive after 5 years, while the 5-year survival rate was 34.1% in Bax-negative patients. These results suggest that the appearance of the Bax protein after preoperative chemoradiotherapy is a significant prognostic marker for maxillary SCC.The prognosis for maxillary squamous cell carcinoma (SCC) remains poor, despite advances in combination therapy. Combined treatment with anticancer drugs and radiation therapy is aimed at inducing apoptosis. As apoptosis is regulated by several proteins, we investigated the expression of p53, Bax and Bcl-2 in maxillary SCC before treatment and after preoperative chemoradiotherapy using an immunohistochemical approach. Furthermore, apoptotic cells were visualized using an in situ apoptosis detection kit and the apoptosis index (AI) was defined as the number of positive cancer cells per 1,000 cancer cells. Expression of p53 and Bcl-2 and the Al in 23 maxillary SCCs were not associated with tumor size, lymph node metastasis, clinical stage, frequency of recurrence or 5-year survival rate either before treatment or after preoperative chemoradiotherapy. Bax expression before treatment was not correlated with any clinicopathological factors before treatment. However, no patients in the Bax-positive group (11/22 cases) after preoperative chemoradiotherapy had recurrence of maxillary SCC and all were alive after 5 years, while the 5-year survival rate was 34.1% in Bax-negative patients. These results suggest that the appearance of the Bax protein after preoperative chemoradiotherapy is a significant prognostic marker for maxillary SCC.