The Clinical Research On The Expression Of Cyclooxygenase-2 In The Serum Of Patients With Breast Cancer

Background: Breast cancer is very common in malignant tumors for female, in developed countries the morbility of breast tumor was significantly higher than developing countries. According to statistics,in the United States breast cancer morbility among women malignant is top of the list,in our country its morbidity is also increasing year by year.At present, surgery for breast cancer is still the main treatment,but chemotherapy,radiotherapy and endocrine therapy for breast cancer have been becoming important means of treatment.Endocrine therapy of breast cancer has led to widely benefit for the breast cancer patients. According to the expression of estrogen receptor and progesterone receptor, the endocrine treatment is determined,that has become the clinical treatment guideline.However, such a guideline has met the increasing challenge of a new theory.Since 80's an army of epidemiological survey found that patients with rheumatoid joints long-term eating non-steroidal anti-inflammatory drugs (ie,non-selective COX-inhibitor) had the low incidence of tumor.Therefore,it had launched the high wave in the relationship of COX-2 with tumor occurrence and development.COX-2 is expressed high in various types of epithelial cancer,and in breast cancer has also shown a marked expression.In recent years the abroad testing centers by immunohistochemistry or RT-PCR methods had been detecting breast cancer tissue and adjacent tissues of expression of COX-2.Various laboratories reported that COX-2 expressed in the different periods in breast cancer patients from 36% to 72%.Various experimental results could be due to different detective methods and the sample quantity. The high expression of COX-2 may contribute to precancerous lesions of the cells with proliferation, transformation, inhibition apoptosis, maintaining the activity of tumor cells to promote tumor-specific angiogenesis, promoting tumor growth,invasion,metasta- sis,and spread, suppressing or evading the body's immune function to tumor cells,and enhancing the tumor cells,resistance,reducing the breast cancer cells to the sensitivity of the radiotherapy and chemotherapy. Abroad of substantial experiments discussed the relevance of COX-2 and clinicopathological character- istics of breast cancer,the expression of COX-2 has relevance with patient age,tumor size, histological type,lymph node metastasis, lymphatic infiltrateion, MVD, HER2/-neu, ER, PR, and so no. After a large sample of retrospective studies have also shown that COX-2 and breast tumor recurrence,distant metastasis,survival rate,exist the relevance.Ristimak's study showed that ER, PR negative breast cancer patients, whose COX-2 expression was significantly higher than the ER, PR positive.And ER, PR-negative patients with poor prognosis are related to it.Then ER, PR positive patients express COX-2 is still poor prognosis. New adjuvant endocrine therapy that aromatase inhibitors united cycloo- xygenase inhibitor has become the consensus, and whose clinical studies receive good results. AIs united cyclooxygenase inhibitors new adjuvant therapy compared to the single AIs for patients with breast cancer,New adjuvant therapy group has reduced even more obvious the concentration of serum CA153. But cyclooxygenase-2 whether high expression of breast cancer specificity and sensitivity of clinical detection of indicators can not be determined.Using immunohistochemical detection expression of tissue COX-2,can only be carried out COX-2 qualitative research,and should not carry out quantitative detection, although the RT-PCR of COX-2 can be quantitatively detected,but also unable to provide postoperative COX-2 expression.Using serum enzyme-linked imm- unosorbent assay method can be carried out quantitative research,can detect the preoperative and postoperative serum of patients with the change of COX-2,and provide a guarantee for further study of COX-2,testing results can be generalized response in COX-2 expression with patients'whole body state.Objective: Detect breast cancer patients preoperative and postoperative serum levels of cyclooxygenase-2,and explore the breast cancer patients with COX-2 expression and the relation with cyclooxygenase-2 and the clinicopathological characteristics of breast cancer.Methods: Selected in January 2007-June 2008 pathological examination confirmed to be breast cancer patients,preoperative patients blood, 30 cases as the preoperative group,corresponding breast surgery including breast conserving surgery,radical mastectomy or modified radical mastectomy postoperative 14 days of the 27 cases as postoperative group.Confirmed by postoperative pathology of 13 cases of breast adenosis as adenosis group,and the same period workers for health examination 13 cases as healthy normal control group. Healthy normal control group at the medical examination day took three milliliters venous blood, patients with breast cancer were admitted to collect 3 milliliters the second day morning fasting venous blood, and collect the 14th day after surgery 3 milliliters morning fasting venous blood, patients with breast adenosis also admitted on the after 2nd morning colleted 3 milliliters of morning fasting venous blood, all samples were solidified after standing at room temperature centrifugation(3000r/min,4℃), separation of serum,placed in-80℃refrigerator to preserve back-up. All groups were detected expression of COX-2 in serum by enzyme-linked immunosorbent assay (ELISA).Results:⑴.Healthy control group,adenosis of breast group and cancer group all patients'age had no statistically difference (P>0.05).(2).Serum of preoperative breast cancer group with postoperative breast cancer group of the levels of COX-2 were significantly higher than the control group,with statistical significance (P<0.01).Serum of patients with breast adenosis group of levels of COX-2 comparing to the normal control group had no significant statistics difference (P>0.05);Serum of patients with postoperative breast cancer group of levels of COX-2 were significantly higher than the breast adenosis group, with statistical significance (p<0.01);Serum of preoperative breast cancer group of levels of COX-2 were significantly higher than the adenosis of breast group, with statistical significance (p<0.01);(3).Breast carcinoma in situ and invasive ductal carcinoma and lobular carcinoma in patients with COX-2 levels had no the statistically difference (P>0.05).Breast cancer patients with stageⅢ+Ⅳin serum of COX-2 levels comparing to patients with stage Tis+Ⅰ+Ⅱhad no statistically difference (P>0.05).The tumor size less than 2 centimeters of breast cancer patients,size greater than 2 centimeters and less than 5 cm of the patients and greater than 5 cm in patients with COX-2 levels had no statistically difference (P>0.05),serum level of COX-2 in patients with lymph node metastasis were significantly higher than without lymph node metastasis in patients, with statistical significance (P<0.05),ER-negative patients had higher level of COX-2 than ER positive, with statistical significance (P<0.01),PR positive patients expressed the level of COX-2 than negative patients had no statistically difference (P>0.05),HER-2 positive sera of patients expressed COX-2 level were higher than the negative patients, with statistical significance (P<0.01).Conclusion: Breast cancer patients with preoperative serum of COX-2 levels were significantly higher than the normal control group and breast adenosis group,serum levels of COX-2 in breast cancer detection can be used as a candidate diagnostic indicator,and can be used for benign and malignant breast disease diagnosis.Preoperative patients with lymph node metastasis group were higher than without lymph node,ER-negative patients with COX-2 levels were higher than the positive patients,HER-2 positive sera of patients with COX-2 levels were higher than the HER-2 negative patients.This method was easy to draw the materials from peripheral blood,easy operated and the necessary equipment was simple,good repeatability,easy to promote in vivo expression of cyclooxygenase dynamic tracking,for breast cancer early detection,monitoring relapse,prognosis having good clinical practical value.