The Correlation of Neoadjuvant Chemotherapy Responsiveness with The Expression of BCL-2, Bax, VEGF, PCNA and The Pattern of Apoptosis in Cervical Cancer

Kim, Yong Beom; Park, Noh Hyun; Park, In Ae; Lee, Hyo Pyo

Abstract

The purpose of this study was to identify the relationship between the clinical response to neoadjuvant chemotherapy and PCNA and VEGF protein expression, apoptosis and its related gene expression such as Bcl-2 and Bax in cervical cancer. We retrospectively reviewed 30 patients with locally advanced or bulky cervical cancer treated with three courses of neoadjuvant chemotherapy followed by radical hysterectomy or radiation therapy at Seoul National University Hospital from June 1995 to June 1998. The specimen were obtained before chemotherapy by colposcopy directed biopsy. The protein expressions of Bcl-2, Bax, VEGF and PCNA were examined by immunohisto- chemical staining and the apoptosis was examined by TUNEL staining. These results were compared with chemotherapeutical response which was evaluated by colposcopy or CT/MRI. There were 2 CR(complete response), 19 PR(partial response) and 9 NC(no change) and there was no progressive disease. There was no significant difference between responder and nonresponder according to the age, tumor size and FIGO stage. The 3 year survival rates of responder and nonresponder were 90.0% and 66.7% respectively and there was significant difference between two groups(p=0,015). The expression of Bcl-2 and Bax was positive in 23.3%(7/30) and 46.7%(14/30). The expression of VEGF was positive in 83.3%(25/30). PCNA PI(positive index), defined as PCNA positive cells in percentage was more than 25.0% in 20 cases. Apoptotic index, defined as the number of the cells undergoing apoptosis per 1,000 tumor cells, ranged from 3 to 53(mean 22.3). Although there was no significant relationship between the clinical response to neoadjuvant chemotherapy and the expre- ssion of Bcl-2, Bax, VEGF and PCNA PI, apoptotic index was significantly higher in responder than nonresponder when the cutoff value of positive was defined as apoptotic index more than 5(p=0.032). In conclusion, the evaluation of the pattern of apoptosis before neoadjuvant chemothera- py is potentially useful for the prediction ofz tumor response to neoadjuvant chemotherapy for cervical cancer.