ORIGINAL ARTICLE Bali Medical Journal (Bali Med J) 2016. Volume 5. Number 2: 335-339 P-ISSN. E-ISSN. Caspase-3 expression correlation with cell differentiation grade, stage, and residual tumor size in epithelial ovarian cancer CrossMark I Nyoman Gede Budiana* Published by DiscoverSys ABSTRACT Background: Ovarian cancer has a high incidence and a high mortality rate, and often found in terminal stage. In ovarian malignancy, one of the important proteins presents in the apoptosis process is Caspase-3. Caspase-3 has an important role in modifying the cell morphologic and several biochemistry condition of the apoptosis process. Objectives: Our study aims to analyze the correlation between Caspase-3 expression and the cell differentiation grade, the stage of the disease, and the residual tumor size after primary surgery in epithelial ovarian cancer. Method: We conducted a cross-sectional study. The sample was recruited in Dr. Soetomo Hospital Surabaya. They were ovarian cancer patients with complete medical records, which ovarian tumor specimens were deparaffinized in the pathology anatomy laboratory. Faculty of Medicine. Airlangga University. Surabaya. Indonesia. Patients were excluded if they received a chemotherapy or a radiotherapy before the surgery, or their paraffin wax embedded tissue were damaged. The Caspase-3 expression was examined immunohistochemically. The correlation among the variables were analyzed using the Spearman and Phi correlation test. Results: From 42 patients. Caspase-3 expression was positive in the 6%, while the 52. 4% was negative. It was found that most samples with a good grade of cell differentiation showed a positive Caspase-3 expression . =-0. 215, p<0. Moreover, in most samples with the early stage of the disease had a positive Caspase-3 expression (I= Ae0. 583, p<0. In addition, most samples with residual tumor less than 1 cm in diameter, also showed a positive Caspase-3 expression (I=-0. 336, p=0. Conclusion: A statistically significant negative correlation was present between Caspase-3 expression and the cell differentiation grade, the stage of the disease, and the residual tumor after the primary surgery. Keywords: Caspase-3. Grade Of Cell Differentiation. Stage Of Disease. Residual Tumor Cite This Article: Budiana. Caspase-3 expression correlation with cell differentiation grade, stage, and residual tumor size in epithelial ovarian cancer. Bali Medical Journal 5. : 335-339. DOI:10. 15562/bmj. Obstetrician and Gynecologist. Teaching Staff. Oncogynecology Division. Department of Obstetrics and Gynecology Faculty of Medicine. Udayana University. Sanglah General Hospital Denpasar. Bali Correspondence to: I Nyoman Gede Budiana. Oncogynecology Division. Department of Obstetrics and Gynecology. Faculty of Medicine. Udayana University. Sanglah General Hospital Denpasar. Bali budiana1971@gmail. INTRODUCTION Ovarian cancer remains as a big health problem in the world and in Indonesia. It has a high incidence and a high mortality rate. In 2008, the global prevalence of ovarian cancer was 9. 1,2 Based on Cancer Registry Agency of the Indonesian Ministry of Health record, which data were collated from 13 centers of pathology anatomy laboratories, the incidence of ovarian cancer was 4. Several medical center in Indonesia reported the incidence as high as 19. 6% to 35%. 3,4 In addition to the high incidence, ovarian cancer has the highest mortality rate among other gynecology Although the prevalence of ovarian cancer is the third highest, which comes after cervical and breast cancer, this malignancy is the most prevalent cause of death in gynecology malignancy There are many prognostic factors influencing the outcome of the ovarian cancer patient, i. the stage, the degree of cell differentiation and the residual tumor size after a primary operation. Open access: w. org and ojs. id/index. php/bmj As much as 70-75% of cases diagnosed in the terminal stage, contributing to the high mortality rate. The 5-year survival rate is 20-30%. But, when diagnosed in the early stage . irst stag. , the 5-year survival rate is 90-95%. 5 The degree of cell differentiation is evaluated using a microscope to determine the morphology characteristic, the aggressivity or the biologic behavior of the cancer cell. The residual tumor size is related to the clinical response to chemotherapy and the survival rate. Numerous research was conducted around the molecular biology aspects of ovarian cancer, especially about the apoptosis process. One of the proteins performing a major role in apoptosis process is Caspase-3. It presence in an apoptosis process is activated by an extrinsic or an intrinsic Caspase-3 plays a role in the cell morphologic change and in various biochemistry related to apoptosis process. 7 This research aimed to discover the correlation between the Caspase-3 expression ORIGINAL ARTICLE and the degree of cell differentiation, the stage and the tumor residue in epithelial ovarian cancer. METHODS We conducted a cross-sectional study in August 2012 to March 2013. The sample was the ovarian cancer patients whose ovarian tumor specimen was deparaffinized in the pathology anatomy laboratory of Dr. Soetomo Hospital in Surabaya. East Java. Indonesia. The inclusion criteria were: the patientAos histopathology examination . araffin specime. showed an epithelial ovarian cancer, . the patient has a complete medical The exclusion criteria were: . received a chemotherapy or a radiotherapy before a specimen was taken, . the paraffin specimen was found damaged. The Caspase-3 expression was examined using an immunochemistry technique by utilizing NovocastraTM Lyophilized Mouse Monoclonal Antibody CPP32 (Caspase-. staining produced by Leica Biosystem Newcastle Ltd. -United Kingdom. The Caspase-3 expression interpretation was done semi-quantitatively by counting the percentage of the positive malignant cells in 200 malignant cells, using an Olympus binocular light microscope in 400x magnification. The staining was positive if the nucleus and or the cytoplasm becomes brown. The scoring was based on the percentage of the stained nucleus and or the cytoplasm. The scoring criteria were: 0 if there was no stained nucleus and or cytoplasm, 1 if 1 to 10% of the nucleus or the cytoplasm was stained, 3 if there was more than 10% of the nucleus or the cytoplasm stained. 8 The Caspase-3 expression was categorized into negative for the 0 and the 1, and claimed as positive if it scored 2 or 3. The ovarian cancer degree of differentiation was classified according to Shimizu-Silverberg grading The scoring is based on the cell component . landular, papillary, or soli. , the degree of atypical nucleus . ild, moderate, sever. , and the mitotic index per 10 HPF . -9, 10-24, and Ou. The score from each component was then summarized as a total score to determine the degree of differentiation. 9 The grading system consists of 3 degrees of differentiation: 1st degree or a good differentiation if the score 3-5, 2nd degree or a moderate differentiation if the score 6-7, and 3rd degree or a poor differentiation if the score 8-9. The primary surgery result and the metastatic finding in the patient medical record used the ovarian cancer staging based on the International Federation of Gynecology and Obstetrics (FIGO) 2008 classification. The stages are: early stage for stage I and II, and advance stage for stage i and IV. The residual tumor size is the largest diameter of the tumor left after the primary surgery. The criteria of the tumor residue size are: optimal if the residual tumor diameter is less or the same as 1 cm, and suboptimal if the residual tumor so more than 1 cm. 13 The Spearman correlation test and Phi association test was conducted to examine the statistical correlation between the variables. RESULTS There were 42 patients included in our study. The youngest was 25 and the oldest was 70, with average age of 47. 5A9. 6 years. In 47. 6% of the sample, the Caspase-3 expression was positive, while the rest was negative . 4%). Table 1 C haracteristics Based on Age. Parity. Histopathology. Degree of Differentiation. Disease Stage. Tumor Residual Size Characteristics 21 Ae 30 31 Ae 40 41 Ae 50 51 Ae 60 > 60 Endometrioid Serous Mucinous Clear-cell Good Moderate Poor Early Advance O 1 cm > 1 cm Age . n yea. Parity Histopathology Degree of Differentiation Ovarian cancer stage Tumor residual Published by DiscoverSys | Bali Med J 2016. : 335-339 | doi: 10. 15562/bmj. ORIGINAL ARTICLE Table 2 D istribution Based on Caspase-3 Expression and The Cell Differentiation Cell degree of Caspase-3 expression Negative f (%) Positive f (%) Total f (%) 4 . Total f (%) 22 . Spearman correlation test. r=-0. p=0. Table 3 Distribution Based on Caspase-3 Expression and Staging Caspase-3 expression Stage Negative f (%) Positive f (%) Total f (%) Early 2 . Advance 20 . Total (%) 22 . Phi association test. I=-0. p<0. Table 4 D istribution Based on Caspase-3 Expression and Residual Tumor Size Caspase-3 Expression Residual Tumor Size Negative f (%) Positive f (%) Total f (%) O 1 cm 8 . > 1 cm 14 . Total (%) 22 . Phi association test. I=-0. p=0. DISCUSSION