The Relationship Between Expressions Of PCNA, Ki-67 And The Radiosensitivity, Prognosis Of Middle-late Phase Cervical Cancer

IntroductionRadiation therapy is a mainstay of treatment for patients with middle - late phase cervical cancer. Due to different patients have different radiosensitivity, so probe predictors of radiosensitivity in selecting an individual radiotherapy for patients with middle — late phase cervical cancer have an important significance. This study collects 36 middle - late phase cervical cancer cases and detects PCNA and Ki-67 expression levels of pre - radioactive and following irradiation biopsy samples by using the method of immunohistochemistry, then evaluates the relationship between expression levels of PCNA and Ki-67 and radiosensitivity and prognosis in patients with middle - late phase cervical cancer.Materials and methods1 . MaterialsBetween Mar 2002 and Mar 2004,36 patients with middle - late phase cervical cancer treated with primal radiation therapy in second affiliate hospital of China medical university. The age ranged from 35 to 74years (median age 45 years ). There were 33 squamous cell carcinoma cases and 3 adenocarcinoma cases. Diameter of tumors of 15 patients were ≥4cm and of 21 patients were < 4cm. According to WHO1995staging classification , there were 18 patients in stage II_b ,14 in stage HI ,4 in stage IV. All 36 patients had not contraindications of radiotherapy and KPS >70. All patients were treated by 6 MV X - ray accelerator therapy. The prescribed external radiotion dose was D_T =40 ~44Gy/20 ~22f/28 ~30d. According to results of re -examination in 2 ~ 3 weeks, operating or receiving radical radiotherapy (D_T =60 ~70Gy) was determined. Response of primary tumor to radiotherapy was classified into complete response (CR) , partial response ( PR) , no change ( NC) and progress disease ( PD) , according to the criterion of therapeutic evaluation ( WHO). The CR regarded as radiosensitive tumor. PR regarded as low radiosensitive tumor. The follow - up was one years. CR or PR was defined as prognosis was good. NC or PD or death because of cervical cancer was defined as prognosis was bad.2 . MethodsBiopsy specimens of all primary tumor before/after irradiation were studied. Streptavidin — peroxidase (SP) irnmunohistochemistry (IHC) method was used to detect expressions of PCNA and Ki-67 in middle - late phase cervical cancer tissues. The irnmunohistochemistry stained sections were judged positive when brown particles appear in nucleus for PCNA and Ki-67. PCNA positive index = the percentage of positive cells relative to the total numbers of tumor cells examined. The positive index ≤5% was no expression( - ) for PCNA and Ki-67. The positive index ≤50% was low expression ( + ) , >50% was high expression( ++ ) for PCNA. Ki-67 positive index = the percentage of positive cells relative to the total numbers of tumor cells examined. The positive index ≤ 25% was low expression( + ) , >25% was high expression( + + ) for Ki-67.3. Statistical analysisStatistical analysis was performed using SPSS10. 0 software. According to different features of data, T - test, x~2 test, Spearson correlation analysis and Logistic regression analysis were performed.Results1. Expressions of PCNA and Ki-67 compared pre - radiotherapy group to after radiotherapy group in middle - late phase cervical cancer.In all 36 patients, the expression of PCNA with 31 patients and of Ki-67 with 32 patients in after radiotherapy group was obviously lower than those in pre - radiotherapy group (P < 0.01).2. The relationship between expressions of PCNA, Ki-67 before irradiation and the radiosensitivity of middle - late phase cervical cancer.36 patients of middle - late phase cervical cancer all achieved to CR or PR after conventional radiotherapy (DT =40 ~44Gy). High expression rate of PCNA and Ki-67 in high radiosensitivity group was obviously higher than those in low radiosensitivity group. Those were 88. 24% (15/17) , 64. 71% (11/17) and 31. 58% (6/19) , 15. 79 (3/19), respectively, in high radiosensitivity group and low radiosensitivity group (P < 0.05).3. The relationship between expressions of PCNA, Ki-67 before irradiation and prognosis of middle - late phase cervical cancer.All patients followed up one year. High expression rate of PCNA in prognosis good group was obviously lower than those in prognosis bad group. It was 37. 50% (9/24) , 100. 0% ( 12/12) , respectively, in prognosis good group and prognosis bad group (P < 0. 05 ). However, high expression rate of Ki-67 was 25.00% (9/24) , 66.67% (8/12) , respectively, in two groups (P>0.05).4. The relationship between the co - detection of PCNA and Ki-67 before irradiation and the radiosensitivity, prognosis of middle - late phase cervical cancer.The radiosensitivity and prognosis in both PCNA and Ki-67 ≥ ++ group were obviously different from one of two ≥ ++ group, other conditions group (P <0.01). However, the radiosensitivity in one of two ≥ ++ group did not show different from other conditions group (P >0.01).5. The relationship between the expression of PCNA and the expression of Ki-67 before irradiation for middle - late phase cervical cancer.Of 36 patients, the expression of PCNA was magnificence positive correlation with the expression of Ki-67 before irradiation for middle - late phase cervical cancer by pearson correlation test (r=0.771, p<0.01).6. Multivariate analysis of radiosensitivity for middle - late phase cervical cancer.Logistic multivariate regression analysis showed that significant influencing factors of radiosensitivity were PCNA and differentiation degree for middle - late phase cervical cancer.DiscussionBoth PCNA and Ki-67 are biologic markers of cells propagating information. It is few report that how to change PCNA and Ki-67 of cervical cancer cells after irradiation. Usually, expression indexe of PCNA and Ki-67 increase after been irradiated 10Gy, tend to stability after 20Gy, decrease after 30 ~40Gy. 36 patients of middle - late phase cervical cancer were irradiated 40 ~ 44 Gy (external radiation) in the study. It also suggests that expressions index of PCNA and Ki-67 decreases obviously. Synthesizing above studies, we think that radiotherapy also can affect cancer cells, s propagation when it directly kills cervical cancer cells. So, PCNA and Ki-67 can be used as biologic markers that reflect propagating information of cervical cancer cells.In recent years, most scholars thinks that expression degree PCNA and Ki-67 are positive correlation with radiosensitivity of cancer cells. They are in accordance with this finding. So, PCNA and Ki-67 can be used as biologic markers that predict radiosensitivity of middle - late phase cervical cancer. They offer worthy references to determine accurate, reasonable and individual treatment project in clinical. At the present time, domestic and international studies are always disputing about the relationship between expressions of PCNA, Ki-67 and the prognosis of cervical cancer after radiotherapy. In this study, 36 middle -late phase cervical cancer patients followed up one year after radiotherapy. It suggests that expression degree of PCNA and Ki-67 increasing is along with progress of cervical cancer decreasing. But, statistical analysis showes that Ki-67 group is not significance ( P > 0. 05 ). So, we think that expression degree of PCNA before irradiation is negative correlation with prognosis of middle - late phase cervical cancer. PCNA can be a worthy biologic marker that predicts the prognosis of middle - late phase cervical cancer after radiotherapy. But, we ought to further researcher because bias factors of affecting the prognosis is much.In this study, the expression index of PCNA was magnificence positive correlation with the expression index of Ki-67 before irradiation for middle - late...