The Prognostic Value of the Expression of SMC4 mRNA in Breast Cancer.

AIM: To investigate the mRNA expression and clinical significance of structural maintenance of chromosomes protein 4 (SMC4) in breast cancer. METHODS: A total of 23 paired samples were sequenced, and data from the Cancer Genome Atlas were analyzed. RESULTS: SMC4 mRNA level was significantly upregulated in breast cancer tissues (P < 0.001). Patients with high mRNA expression of SMC4 had significantly poor survival (P = 0.012). Subgroup analyses show that in nontriple negative breast cancer (non-TNBC) patients, the high SMC4 mRNA expression, older age (>65), negative progesterone receptor, and advanced stages (III-IV) were independent risk factors (HR = 3.293, 95% CI 1.257-8.625, P = 0.015). In patients with TNBC, high mRNA expression of SMC4 correlated with better survival rate (P < 0.046). CONCLUSION: SMC4 mRNA level is a good prognostic biomarker for patients with breast cancer.

A novel tumor suppressor gene NCOA5 is correlated with progression in papillary thyroid carcinoma.

BACKGROUND: In contrast to the excellent prognosis for papillary thyroid carcinoma (PTC), the high incidence of lymph node metastasis (LNM) markedly increases the risk of recurrence and secondary surgery. Thus, novel biomarkers must be urgently identified to assess LNM for patients with PTC. NCOA5 is deeply involved in the progression of human cancer; however, its role in thyroid cancer remains unknown. PATIENTS AND METHODS: Quantitative real-time polymerase chain reaction was conducted to investigate the expression of NCOA5 in PTC. RNA-seq data from The Cancer Genome Atlas (TCGA) database were downloaded to further understand the role of NCOA5 in PTC and its relationship with LNM. RESULTS: NCOA5 was significantly downregulated in PTC tissues when compared with that in adjacent noncancerous thyroid tissues both in our local cohort and TCGA database. Reduced expression of NCOA5 was significantly associated with aggressive clinicopathological features, including histological type, tumor stage, BRAF-V600E mutation, LNM, extrathyroid extension, and clinical stage. Moreover, logistic analysis indicated that reduced expression of NCOA5, age, histological type, and clinical stage are independent high-risk factors for LNM in PTC. CONCLUSION: Our study provides new insights and evidence that NOCA5 was significantly correlated with the progression of PTC and was particularly involved in LNM.

MLF1IP promotes cells proliferation and apoptosis by regulating CyclinD1 in breast cancer.

Breast cancer is the most frequently diagnosed cancer and the leading causes of cancer death among females in worldwide. It is urgent to develop novel biomarkers to improve risk stratification and optimize therapy choice. In our previous study, we firstly found that MLF1IP was upregulated in breast cancer tissue compared with adjacent normal tissue and patients with high MLF1IP expression had significantly lower overall survival. However, the biological function and cellular mechanisms of MLF1IP in breast cancer is still need to be elucidated. Here, we further investigated the role of MLF1IP in breast cancer by in vivo experiments. Our results showed that the expression level of MLF1IP was associated with lymph nodes metastasis and tumor size in clinical characteristic features. By biological function experiment, we found MLF1IP is correlated with cell proliferation and apoptosis and arrest cell cycle G1 through regulating Cyclin D1. Taken together, our findings suggested that MLF1IP could contribute to the oncogenic potential of breast cancer. To the best of our knowledge, it was firstly reported that MLF1IP was involved in breast cancer. This study provided a potential new marker and a target for gene therapy in breast cancer treatment.

NCOA5 is correlated with progression and prognosis in luminal breast cancer.

Nuclear receptor coactivator 5 (NCOA5) is known to modulate ERα-mediated transcription and has been found to be involved in the progression of several malignancies. However, the potential correlation between NCOA5 and clinical outcome in patients with luminal breast cancer remains unknown. In the present study, we demonstrated that NCOA5 was significantly up-regulated in luminal breast cancer tissues compared with adjacent non-cancerous tissues both in validated cohort and TCGA cohort. Moreover, Kaplan-Meier analysis indicated that patients with high NOCA5 expression had significantly lower overall survival (P = 0.021). Cox regression analysis indicated that the high NOCA5 expression was independent high risk factor as well as old age (>60) and HER-2 expression (P = 0.039; P = 0.003; P = 0.005; respectively). This study provides new insights and evidences that NOCA5 over-expression was significantly correlated with progression and prognosis in luminal breast cancer. However, the precise cellular mechanisms for NOCA5 in luminal breast cancer need to be further explored.

MLF1IP is correlated with progression and prognosis in luminal breast cancer.

Myeloid leukemia factor 1-interacting protein (MLF1IP) has been found to be involved in the progression of several malignancies. The potential correlation between MLF1IP and clinical outcome in patients with luminal breast cancer, however, remains unknown. In the present study, we demonstrated that MLF1IP was significantly upregulated in luminal breast cancer tissue compared with adjacent normal tissue both in validated cohort and TCGA cohort. Upregulated expression of MLF1IP was correlated with more often lymph node metastasis and negative progesterone receptor expression in TCGA cohorts. Kaplan-Meier analysis indicated that patients with high MLF1IP expression had significantly lower overall survival. Moreover, multivariate analysis revealed that high MLF1IP expression was independent high risk factor as well as old age (>60) and distant metastasis. This study provides new insights and evidences that MLF1IP over-expression plays important roles in progression of luminal breast cancer. However, the precise cellular mechanisms for MLF1IP in luminal breast cancer need to be further explored.

Primary ectopic substernal thyroid cancer with trachea relapse: a case report and opinions of management.

BACKGROUND: Ectopic substernal thyroid is a rare symptom of thyroid disease that entirely results from the developmental defects at early stages of thyroid embryogenesis and during its descent. Cases were seldom reported as primary ectopic substernal thyroid cancer, especially those with severe local invasion and tracheal relapse. CASE PRESENTATION: In this report, the patient presented odynophagia and a sense of progressing swallowing obstruction. She underwent total thyroidectomy and lump resection. However, she refused to use postoperative radioactive iodine or take adjuvant external-beam radiotherapy, except for thyroid hormone replacement therapy. Tracheal relapse was observed after 6 months. Tracheal stent was used to reconstruct the airway twice. CONCLUSIONS: Trachea invasion might be a worse independent predictor of prognosis than any others and should be given particular attention. Furthermore, tracheal stent might be a palliative option for patients with tracheal relapse.

Prognostic Value of Chemotherapy-Induced Neutropenia at the First Cycle in Invasive Breast Cancer.

Chemotherapy-induced neutropenia (CIN) was the most apparent side effects of bone marrow suppression with adjuvant chemotherapy. Recently, several studies revealed that CIN may predict better outcomes. However, the researches upon breast cancer were still indefinite. We reviewed the female patients with pathologically diagnosed invasive breast cancer at the First Affiliated Hospital of Wenzhou Medical University, between Jan 2008 and Dec 2010. The lowest neutrophil counts in the second week after the first cycle of chemotherapy were collected. Clinicopathological characteristics and survival rates were compared and analyzed between the CIN group and non-CIN group. The median follow-up time was 62 months. The differences of over-all survival and local recurrence-free survival between the 2 groups were nonsense (P = 0.938, P = 0.695, respectively). But the disease-free survival and distant metastasis-free survival of the CIN group were statically significantly better (HR = 0.391, P = 0.009, and HR = 0.315, P = 0.005, respectively). The bone metastasis-free survival may be responsible for the differences (HR = 0.469, P = 0.005). Subgroup analyses showed the CIN may predict lower bone metastases rates with ER positive status, premenopause or younger age (≤ 40) (P = 0.002, P = 0.004, and P = 0.0001, respectively). Cox analysis showed younger ages, N staging, and the presence of CIN were associated with bone metastasis-free survival independently adjusting to peritumoral vascular invasion (P < 0.05). CIN may predict a decreased recurrence risk of breast cancer, especially bone metastases.

Utility of Red Cell Distribution Width as a Prognostic Factor in Young Breast Cancer Patients.

The prognosis of breast cancer occurs in young women is usually poor. Red cell distribution width (RDW), 1 of many routinely examined parameters, has recently been proposed as a prognostic marker in solid tumors. The aim of our study was to assess the predictive value of RDW for survival in young women with breast cancer.We reviewed 203 consecutive young female patients (under 40) with invasive breast cancer diagnosed at the First Affiliated Hospital of Wenzhou Medical University between January 2008 and December 2012. Preoperational RDW, clinicopathological information, and prognostic data were collected. RDW levels were divided into 2 groups: 161 patients with low RDW (≤13.75%) and 42 patients with high RDW (>13.75%). Clinicopathological differences between the 2 groups were calculated by chi-squared test and Wilcoxon rank-sum test. Kaplan-Meier survival analysis and Cox proportional hazard regression analyses were used to examine the effect of RDW on survival.We found that high RDW was significantly associated with larger tumor size (P = 0.002), positive lymph node metastases (P = 0.011), and advanced stages (P = 0.004). Patients with high RDW showed significantly lower disease-free survival (DFS; P < 0.001) and lower overall survival (OS) rate (P < 0.001) than patients with low RDW. Moreover, the Cox regression multivariate analysis revealed that high pretreatment DRW was independently correlated with poor DFS and OS, with hazard ratio 4.819 (95% confidence interval [CI] 2.291-10.138, P < 0.001) and 5.887 (95% CI 1.666-20.802, P = 0.006), respectively.In conclusion, our study demonstrated that pretreatment RDW may be associated with DFS and OS in young women with breast cancer. Further validation and feasibility studies are required before the result of our study can be considered for clinical practice.

Lymphangiogenesis in breast cancer is associated with non-sentinel lymph node metastases in sentinel node positive patients.

Axillary lymph node dissection (ALND) is not suggested in breast cancer patients with negative sentinel lymph node (SLN) biopsies, and SLN is the only positive node in 40-70% of the remaining cases. To distinguish a subgroup in which ALND would be omitted, we investigated the role of lymphangiogenesis in primary breast cancer as a risk factor for distal lymph node involvements in patients with positive SLNs. 86 patients were included in this study. The frequency of proliferative lymphatic endothelial cells (LECP%) was evaluated in each specimen after immunohistochemical double staining for D2-40 and Ki-67. Larger primary tumor size, increased number of positive SLNs, lymphatic vessel invasion and LECP% were significantly associated with non-SLN metastases in the univariate analysis, but only LECP% retained significance in the multivariate model. A positive correlation between LECP% and lymphatic vessel invasion was also revealed. Our study confirmed the important role of lymphangiogenesis in tumor spread, and suggested that LECP% is a promising predictor for additional axillary lymph node involvements.

Ultrasonographic findings of triple-negative breast cancer.

OBJECTIVE: Our aim was to determine whether triple-negative breast cancer (TNBC) has distinguishing sonographic features compared to non-TNBC. METHODS: Data from 145 consecutive breast cancer patients were collected. The images were reevaluated by two dedicated breast imaging experts according to the Breast Imaging Reporting and Data System. The sonographic features of 45 TNBC patients were compared with those of 100 non-TNBC patients. RESULTS: TNBC showed a high histological tumor grade. On ultrasound, TNBC was more frequently to present as oval or round mass shape (48.9%, 17.8%; respectively), more likely to have circumscribed margins (82.2%), and less likely to show posterior attenuating (8.9%). Additionally, compared with non-TNBC, TNBC was less likely to have calcification (35.6%). CONCLUSION: TNBC has distinguishing imaging features on breast ultrasound, and more likely to be associated with benign masses. Knowledge of the distinct sonographic features would be useful in diagnosing TNBC.

Successful use of bevacizumb and paclitaxel in a male breast cancer with liver metastases.

Breast cancer in men is a rare cancer manifestation. In this article we report a case of male breast cancer with liver metastases, which showed a good response to a combined treatment of bevacizumb and paclitaxel, suggesting a useful option for the first-line treatment of patients with recurrent HER2-negative male breast cancer. And further assessment in a randomized clinical trial is needed.

Thymectomy in central lymph node dissection for papillary thyroid cancer.

BACKGROUND: Central lymph node dissection (CND) has been proposed in the treatment of patients affected by papillary thyroid cancer (PTC) with clinically negative neck lymph nodes. The procedure allows pathologic staging of lymph nodes of the central compartment and treatment of the micrometastases. By comparing bilateral and unilateral thymectomy during total thyroidectomy with central lymph node dissection for postoperative complications in sonographically node-negative papillary thyroid carcinomas, we aimed to determine the optimal extent of prophylactic central lymph node dissection. METHODS: Patients were divided into two study groups: Group 1, total thyroidectomy plus unilateral thymectomy during the CND; Group 2, total thyroidectomy associated with bilateral thymectomy (both upper poles) during the CND. Primary endpoints of the study were evaluated by comparing the postoperative complications between the two groups. RESULTS: The only significant result found when comparing the two groups was the rate of transient hypocalcemia. (Group 1: 13.7%, Group 2: 52.4%, p<0.01). A total of five cases of papillary thymic metastases were found in this study. And final pathology confirmed that all cases of thymic metastases were lymph node micrometastases of PTC, only situated in the ipsilateral thymus upper pole. CONCLUSIONS: Bilateral thymectomy during the CND did not provide a better carcinologic resection, as no contralateral thymic metastases were found. The unilateral thymectomy with total thyroidectomy during the CND may represent an effective strategy for reducing the rate of postoperative hypocalcemia.

Down-regulation of miRNA-30a in human plasma is a novel marker for breast cancer.

The present study was to evaluate the value of miRNA-30a in plasma as potential tumor marker in detecting breast cancer (BC). Using a novel approach to extract miRNA-30a from the plasma followed by real-time quantitative polymerase chain reaction (RQ-PCR) analysis, levels of miRNA-30a were quantified in plasma specimens of 100 BCs and 64 age-matched and disease-free healthy controls (HC). And we compared the diagnostic value of plasma miRNA-30a with conventional circulating tumor markers CA153 and CEA. The median levels of miRNA-30a were significantly lower in preoperative BC than those in HC (P < 0.001). The levels of CEA and CA153 were all significantly higher in preoperative BC compared with those in HC (P = 0.008 and P = 0.001, respectively), and only the level of CA153 decreased in postoperative BC compared with preoperative BC (P = 0.015). ROC analysis showed the sensitivity and specificity of miRNA-30a for BC diagnosis at 74.0 and 65.6 %, respectively, whereas the sensitivities of CEA and CA153 were 12.0 and 14.0 %, respectively. The status of ER and triple-negative BC was significantly associated with miRNA-30a level (P = 0.007 and P = 0.005, respectively). And no other clinicopathological features were found to had significant difference. Our findings suggest that plasma miRNA-30a decreased in patients with BC and has great potential to use as novel biomarkers for BC diagnosis.

Continued twitching of the latissimus dorsi miniflap after breast conservation therapy: a case report.

We report a case of continued twitching of the latissimus dorsi muscle following breast conservation therapy, along with immediate reconstruction with a latissimus dorsi miniflap, which continued despite several attempts at control including BTX-A percutaneous local injection, and was finally cured by delayed division of the thoracodorsal nerve via a small well-tolerated axillary incision.

[The effect of cyclooxygenase-2 on lymphangiogenesis in breast cancer].

OBJECTIVE: To study the effect of cyclooxygenase-2 (COX-2) on lymphangiogenesis in breast cancer. METHODS: By the means of immunohistochemistry, COX-2, vascular endothelial growth factor-C (VEGF-C) and D2-40 were examined in the tissue samples of primary tumors from 94 patients underwent surgical resections for breast cancer from November 1998 to March 2002. Eighty-three patients were followed-up. The expressions of VEGF-C mRNA and protein were detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot in MDA-MB-231 cell lines by the treatment of selective COX-2 inhibitor Nimesulide at different doses. The expressions of VEGF-C protein were evaluated in MDA-MB-231 cells treated by PGE2 (1 microg/ml) and Trastuzumab (1 microg/ml), respectively. RESULTS: COX-2 over-expression was observed in 46.8% of surgical specimens (44/94), while VEGF-C overexpression occurred in 51.1% of tumor samples (48/94). COX-2 was strongly correlated with VEGF-C expression (P < 0.01), micro-lymphatic vessels (P = 0.032) and metastatic lymph nodes (P = 0. 035). Patients with COX-2 positive tumors had a significant shorter survival time than those with negative tumors did, including disease-free survival (P = 0.010) and overall survival (P = 0.040). Nimesulide could down-regulate the expressions of VEGF-C mRNA and protein in a does-dependent manner, while PGE2 could up-regulate the expressions. The expression of VEGF-C protein up-regulated by PGE2 treatment was decreased by Trastuzumab. CONCLUSIONS: COX-2 over-expression can up-regulate the expression of VEGF-C. VEGF-C might promote lymph node metastasis by a lymph-angiogenic pathway, then affect the prognosis of the patients with breast cancer.

Coexpression of VEGF-C and COX-2 and its association with lymphangiogenesis in human breast cancer.

BACKGROUND: Lymphangiogenesis has become a new research frontier in tumor metastasis since the discovery of reliable lymphatic markers that have allowed observation and isolation of lymphatic endothelium. Cyclooxygenase-2 (COX-2) has been reported to be involved in the critical steps in carcinogenesis. However, possible role of COX-2 in lymphangiogenesis and lymphatic metastasis is still poorly understood. In present study, we aimed to investigate the relationship between vascular endothelial growth factor-C (VEGF-C) and COX-2 in human breast cancer, and correlations with lymphangiogenesis and prognosis. METHODS: Tissue samples of primary tumors from 70 patients undergoing intentionally curative surgical resections for breast cancer were immunohistochemically examined for VEGF-C, COX-2, and D2-40 expressions. The association between COX-2 and VEGF-C expressions and clinicopathological parameters as well as prognosis were analysised. To demonstrate the presence of proliferating lymphatic endothelial cells, 10 random cases with high LVD counts were selected for D2-40/Ki-67 double immunostaining. RESULTS: A significant correlation was found between the expression of VEGF-C and COX-2 (r = 0.529, P < 0.001), and both elevated VEGF-C expression and elevated COX-2 expression were associated with higher lymph vessel density (LVD), lymph node metastasis and D2-40 positive lymphatic invasion (LVI) as well as worse disease free survival (DFS) and overall survival (OS) in a univariate analysis. In the double immunostain for the lymph vessel marker D2-40 and the proliferation marker Ki-67, the results confirmed Ki-67-positive nuclei in a proportion of lymph vessel endothelial cells. CONCLUSION: There is indeed lymphangiogenesis in breast cancer, the most compelling evidence being the presence of proliferating lymphatic endothelial cells. VEGF-C and COX-2 are coexpressed and significantly associated with lymphangiogenesis and prognosis in invasive breast cancer. Suggesting COX-2 may up-regulate VEGF-C expression and thus promote lymph node metastasis via lymphangiogenesis pathway in human breast cancer.