环氧化酶-2和生存素在乳腺癌、癌前病变及普通导管增生中的表达及意义

目的探讨环氧化酶-2(COX-2)和生存素(survivin)在乳腺癌及癌前病变中的表达及意义。 方法选取274例乳腺癌及癌前病变患者为观察组，包括128例乳腺浸润性导管癌(IDC)患者，89例乳腺导管原位癌(DCIS)患者和57例乳腺非典型导管增生(ADH)患者的病变组织；以60例乳腺普通导管增生(UDH)患者作对照。应用免疫组织化学S-P法检测COX-2和survivin在上述组织中的表达，研究：(1)不同组织中阳性表达模式；(2)阳性表达差异；(3)COX-2和survivin在IDC中的表达与临床病理因素包括肿瘤大小、分级、分期及ER、PR、HER-2和Ki-67表达的关系；(4)COX-2和survivin在乳腺癌中表达的相关性。COX-2和survivin在不同组织中表达率的比较用χ²检验，相关性检验采用Spearman等级相关分析。 结果(1)表达模式：COX-2在不同组织中主要表达在细胞质中；survivin在UDH中主要表达在细胞质，而在IDC、DCIS和ADH组织中则在细胞质和细胞核中均有表达，在IDC中survivin在细胞核中表达增多；(2)COX-2和survivin在IDC中的阳性表达率分别为79.5%和67.2%，DCIS为55.1%和59.6%，ADH为42.1%和57.9%，UDH为16.7%和1.7%，与UDH组比较，COX-2和survivin的表达IDC组(χ²＝66.745，70.540)、DCIS组(χ²＝22.084，51.967)和ADH组(χ²＝9.176，42.829)差异均有统计学意义(P<0.05)；(3)COX-2和survivin的表达IDC(79.5%和67.2%)与DCIS(55.1%和59.6%)(χ²＝14.768，P<0.05；χ²＝1.330，P>0.05)、IDC与ADH(42.1%和57.9%)(χ²＝25.293，P<0.05；χ²＝1.484，P>0.05)比较，COX-2的表达差异均有统计学意义(P<0.05)，survivin均无统计学意义(P>0.05)；(4)DCIS与ADH比较，COX-2和survivin的表达差异无统计学意义(χ²＝2.331，0.039；P>0.05)；(5)患者不同年龄、肿瘤大小COX-2和survivin的表达水平差异无统计学意义(P>0.05)，而不同组织学分级、有无淋巴结及远处转移COX-2和survivin的表达水平差异有统计学意义(P<0.05)；(6)COX-2和survivin二者在乳腺癌中的表达呈正相关(r＝0.210，χ²＝5.626，P<0.05)。 结论survivin在乳腺良、恶性病变中表达的不同定位，对乳腺疾病性质的判断具有重要意义；COX-2和survivin高表达是乳腺癌发生、侵袭转移行为的生物学标志，联合检测有望成为评估乳腺癌生物学行为的参考指标。

The expression and significance of cyclooxygenase 2 and survivin in breast carcinoma and precancerous lesions

ObjectaveTo investigate the expression and significance of cyclooxygenase 2 (COX-2) and survivin in breast carcinoma, precancerous lesions and usual duct hyperplasia lesions(UDH). MethodsImmunhistochemical UltraSensitive TM S-P method was applied to detect the expression of COX-2 and survivin in two hundred and seventy-four cases of patients with breast lesions including one hundred and twenty-eight cases with invasive ductal carcinomas(IDC), eighty-nine cases with ductal carcinoma in situ(DCIS), and fifty-seven cases with atypical ductal hyperplasia(ADH). Sixty cases with UDH were selected as a control group.The multiple biological parameters including the tumor size, grade, stage were compared with the associations of COX-2 and survivin expressions in breast carcinoma. ResultsCOX-2 was mainly distributed in cytoplasm in IDC, DCIS, ADH and UDH.survivin was mainly distributed in cytoplasm in UDH, but survivin was also distributed in nucleus and cytoplasm in IDC, DCIS and ADH mammary tissues.The positive rates of COX-2 and survivin were 79.5% and 67.2% in IDC, 55.1% and 59.6 % in DCIS, and 42.1% and 57.9% in ADH, which were higher than those in UDH tissues(16.7%, 1.7%). Compared with UDH, the difference was statistically significant(P<0.05). There were significant differences in the positive expression rates of COX-2 between IDC and DCIS tissues (χ²=14.768, P<0.05), IDC and ADH (χ²=25.293, P<0.05). However, there were no significant differences of survivin expression between IDC(79.5%, 67.2%) and DCIS(55.1%, 59.6%) tissues(χ²=1.330, P>0.05), IDC(79.5%, 67.2%) and ADH(42.1%, 57.9%)(χ²=1.484, P>0.05). Positive rates of COX-2 and survivin were found insignificant between ADH and DCIS tissues (χ²=2.331, P>0.05; χ²=0.039, P>0.05, respectively). There was positive correlation in over-expression of COX-2 and survivin with histological grade, lymph node metastasis, distant metastasis and stage of IDC tumor.And the expression of the two proteins were not related with age and tumor size (P>0.05). The expression of COX-2 was correlated positively with survivin(r=0.210, χ²=5.626, P<0.05). Conclusions- survivin location changes from cell plasma to cell nucleus might participate in oncogenesis and development of breast cancer.The over-expression of COX-2 and survivin might be important biological markers for invasion and metastasis of IDC.The combined detaction of COX-2 and survivin might be the predictors for prognosis and targeting treatment of breat carcinoma.