The Expression And Significance Of Twist In Invasive Micropapillary Carcinoma Of The Breast

Objective:Invasive Micropapillary Carcinoma (IMPC) of the Breast is an unusal subtype of breast cancer with a high incidence of lymph node metastasis and poor prognosis. Recent studies have showed that twist is overexpression in many types of human carcinomas and plays an important role in the invasion and metastasis of the tumors as a metastasis-related gene. The study aims to investigate the expression, location and distribution of Twist in IMPC and invasive ductal carcinoma not otherwise specified (IDC-NOS), their relationship with clinicopathological features was analyzed. The mechanisms of biological behavior with high incidence of axillary lymph node metastases of IMPC were explored from the point view of twist.Methods:The expression, location and distribution of Twist were determined by immunohistochemical SP staining in103cases of IMPC and108cases of invasive ductal carcinoma not otherwise specified (IDC-NOS), undergoing without preoperative chemotherapy and radiotherapy. The correlations between the expression of the protein and clinicopathologic characteristics, which include the prognosis patients was also determined.Results:1. Compared with the control group of IDC-NOS, IMPC were larger in size (t=3.998, P<0.001), higher pTNM staged (H=11.911, P=0.001), had a higher lymph node metastasis rate (χ2=4.712, P=0.030), and exhibited increased lymphovascular invasion (χ2=33.889, P<0.001) and extranodal extension (χ2=6.021, P=0.014), differences were statistically significant.2. According to the percentage of IMPC component in the whole tumor, we divided IMPC into different groups, and then analyzed the relationship between the percentage of IMPC and the expression of Twist, the extent of lymph node metastasis and the patients’prognosis. The percentage of IMPC component in the whole tumor was not significantly associated with the expression of Twist (P=0.066), the extent of lymph node metastasis (P=0.165) and the patients’prognosis (P=0.923).3. Twist was mainly expressed in the plasma of tumor cells, fewer in the nucleus. Twist expressed positively56.3%(58/103) in breast IMPC, significantly higher than IDC-NOS group41.7%(45/108).4. In IMPC, nuclear expression of Twist was negatively correlated with the estrogen receptor (r=-0.301,P=0.002) and was positively correlated with metastasis in lymph nodes (r=0.324,P=0.001)、lymphovascular invasion (r=0.507,P<0.001) and extranodal extension (r=0.428,P<0.001); cytoplasm expression of Twist was only negatively correlated with the estrogen receptor (r=-0.262,P=0.007). No correlation was found between Twist and the patient’s age, tumor size, pathologic stage and progesterone receptor or human epidermal growth factor receptor2.5. Kaplan-Meier analysis indicated that IMPC patients with Twist positive expression showed a lower disease-free survival (DFS) compared to the same patients with Twist negative expression (log-rank test, P=0.002). Multivariate analysis showed that high expression of Twist and lymph nodes status were the independent risk factors that can predict the survival of IMPC patients (RR=2.771and2.202, P<0.046and0.014, respectively).6. Multivariate analysis showed that high expression of Twist and lymph nodes status were also the independent risk factors that can predict the survival of IDC-NOS patients (RR=3.303and3.695, P=0.048and0.009, respectively).Conclusions:1. IMPC had a higher lymph node metastasis rate and poor prognosis.2. The percentage of IMPC components in the whole tumor was not significantly associated with lymph node metastasis rate or the patients’ bad prognosis.3. Twist over-expressed in IMPC compared with IDC-NOS, suggesting that activation of the Twist gene may play a role in the malignant progression of IMPC.4. In IMPC, nuclear expression of Twist was positively correlated with metastasis in lymph nodes、lymphovascular invasion and extranodal extension, indicating that Twist may play an important role in high metastasis of IMPC.5. The expression of Twist in IMPC was negatively correlated with the expression of ER, combined with previous studies, suggesting that for ER-Twist+breast cancer patients, silence Twist may be able to recover the expression of ER and enhance the therapeutic effect of endocrine.6. The risk factors for disease-free survival of patients of IMPC and INC-NOS were associated with high expression of Twist, indicating that high expression of Twist may lead a bad prognosis.