Rabbit thyroid extracellular matrix as a 3D bioscaffold for thyroid bioengineering: a preliminary in vitro study.

BACKGROUND: Advances in regenerative medicine technologies have been strongly proposed in the management of thyroid diseases. Mechanistically, the adoption of thyroid bioengineering requires a scaffold that shares a similar three-dimensional (3D) space structure, biomechanical properties, protein component, and cytokines to the native extracellular matrix (ECM). METHODS: 24 male New Zealand white rabbits were used in this experimental study. The rabbit thyroid glands were decellularized by immersion/agitation decellularization protocol. The 3D thyroid decellularization scaffolds were tested with histological and immunostaining analyses, scanning electron microscopy, DNA quantification, mechanical properties test, cytokine assay and cytotoxicity assays. Meanwhile, the decellularization scaffold were seeded with human thyroid follicular cells, cell proliferation and thyroid peroxidase were determined to explore the biocompatibility in vitro. RESULTS: Notably, through the imaging studies, it was distinctly evident that our protocol intervention minimized cellular materials and maintained the 3D spatial structure, biomechanical properties, ECM composition, and biologic cytokine. Consequently, the decellularization scaffold was seeded with human thyroid follicular cells, thus strongly revealing its potential in reinforcing cell adhesion, proliferation, and preserve important protein expression. CONCLUSIONS: The adoption of our protocol to generate a decellularized thyroid scaffold can potentially be utilized in transplantation to manage thyroid diseases through thyroid bioengineering.

COPB2 is up-regulated in breast cancer and plays a vital role in the metastasis via N-cadherin and Vimentin.

Breast cancer (BC) is a common malignant tumour for the adult female and its relative incidence has increased continuously in recent years. The primary molecular mechanisms of breast tumourigenesis remain unclear. With the sequencing technology, we found that coatomer protein complex subunit beta 2 (COPB2) gene is overexpressed in breast cancer tissues. However, the biological function of COPB2 in BC has yet to be determined. This current research demonstrates, significant up-regulation of COPB2 in tissues of breast cancer while comparing the adjacent normal tissue both invalidated cohort and TCGA cohort. Up-regulated expression of COPB2 was correlated with lymph node metastasis (LNM) and oestrogen receptor (ER) in the TCGA cohort and a high level of COPB2 was associated with age and lymph node metastasis in the validated cohort. Besides, logistic analysis illustrated in BC patient COPB2 expression, tumour size, age, ER and disease stage were independent high-risk factors of LNM. Loss of function experiments revealed that down-regulation of COPB2 could inhibit capacities of proliferation and cell invasion in MDA-MB-231 and BT-549 cell lines. Moreover, underexpression of COPB2 could decrease the EMT-related protein N-cadherin and vimentin which may lead to cell invasion. This current research provides new shreds of evidence that COPB2 overexpression shows significant character in the progression of breast cancer. To best of our knowledge, our findings indicated that COPB2 was vital oncogene which was associated with breast cancer.

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.

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.

Sentinel lymph node biopsy is unsuitable for routine practice in younger female patients with unilateral low-risk papillary thyroid carcinoma.

BACKGROUND: Sentinel lymph node (SLN) biopsy has been used to assess patients with papillary thyroid carcinoma (PTC). To achieve its full potential the rate of SLN identification must be as close to 100 percent as possible. In the present study we compared the combination of preoperative lymphoscintigraphy scanning by sulfur colloid labeled with 99 m Technetium, gamma-probe guided surgery, and methylene blue with methylene blue, alone, for sentinel node identification in younger women with unilateral low-risk PTC. METHODS: From January 2004 to January 2007, 90 female patients, ages 23 to 44 (mean = 35), with unilateral low-risk PTC (T1-2N0M0) were prospectively studied. Mean tumor size was 1.3 cm (range, 0.8-3.7 cm). All patients underwent unilateral modified neck dissection. Prior to surgery, patients had, by random assignment, identification and biopsy of SLNs by methylene blue, alone (Group 1), or by sulfur colloid labeled with 99 m Technetium, gamma-probe guided surgery and methylene blue (Group 2). RESULTS: In the methylene blue group, SLNs were identified in 39 of 45 patients (86.7%). Of the 39 patients, 28 (71.8%) had positive cervical lymph nodes (pN+), and 21 patients (53.8%) had pSLN+. In 7 of the 28 pN+ patients (25%), metastases were also detected in non-SLN, thus giving a false-negative rate (FNR of 38.9% (7/18), a negative predictive value (NPV) of 61.1% (11/18), and an accuracy of 82.1% (32/39). In the combined technique group, the identification rate (IR) of SLN was 100% (45/45). Of the 45 patients, 27 (60.0%) had pN+, 24 (53.3%) had pSLN+. There was a FNR of 14.3% (3/21), a NPV of 85.7% (18/21), and an accuracy of 93.3% (42/45). The combined techniques group was significantly superior to the methylene blue group in IR (p = 0.035). There were no significant differences between two groups in sensitivity, specificity, NPV, or accuracy. Location of pN+ (55 patients) in 84 patients was: level I and V, no patients; level II, 1 patient (1.2%); level III, 6 patients (7.2%); level III and IV, 8 patients (9.5%); level IV, alone, 8 patients (9.5%); level VI, 32 patients (38.1%). In all 90 patients, IR of SLN was 93.3%, FNR, 25.6%, NPV, 74.4%, and accuracy rate, 88.1 percent. CONCLUSIONS: Compared to a single technique, there was a significantly higher SLN identification rate for the combined technique in younger female with ipsilateral, low-risk PTC (T1-2N0M0). Thus, a combined SLN biopsy technique seems to more accurately stage lymph nodes, with better identification of SLN located out of the central compartment. Regardless of the procedure used, the high FNR renders the current SLN techniques unsuitable for routine practice. Based on these results, prophylactic node dissection of level VI might be considered because 38.1% of our patients had such node metastases.

Nuclear Receptor Coactivator 5 is Correlated with Progression in Breast Carcinoma.

BACKGROUND: Breast cancer (BC) is increasingly becoming the primary reason for death in women, which sounded the alarm. Thus, finding a novel management target for BC is imminent. METHODS: The data of gene expression and clinicopathological characteristics were downloaded from The Cancer Genome Atlas (TCGA). The expression of nuclear receptor co-activator 5 (NCOA5) in 35 paired breast cancer and adjacent tissues was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Univariate and Multivariate logistic regression methodology was applied to analyze the prognostic factors for lymph node metastasis (LNM). Based on the status of breast cancer-relative receptors, patients were distributed in six groups, then the Kaplan-Meier survival analysis with log-rank test was applied to investigate the involvement among the expression of NCOA5 and overall survival (OS). RESULTS: The expression of NCOA5 in BC was greater than normal tissues when comparing the data from TCGA. This result had also been verified in our local cohort. The expression of NCOA5 was closely related to LNM, Estrogen receptor (ER) status and progesterone receptor (PR) status. The consequence of Multivariate logistic regression analysis showed that the expression of NCOA5, tumor size, ER status and clinical stage was significantly associated with LN. Moreover, subgroup analyses showed that high expression of NCOA5 is an independent risk factor for OS in patients who were in ER (+) or PR (+) or maybe human epidermal growth factor receptor-2(Her-2) positive status. CONCLUSION: NCOA5 was significantly correlated with LNM in BC. Meanwhile, the expression of NOCA5 could predict the OS time, especially in breast cancer patients whose status of hormone receptor was positive. NCOA5 may act as a promising treatment target to shortening the treatment period and improving the prognosis of ER (+) breast cancer.

Identification and validation of L Antigen Family Member 3 as an immune-related biomarker associated with the progression of papillary thyroid cancer.

BACKGROUND: Papillary thyroid cancer (PTC) is heterogeneous cancer with many different immune cells involved in its pathogenesis. L Antigen Family Member 3 (LAGE3) is an ESO/LAGE gene family member that has not been extensively studied in PTC. METHODS: Comprehensive bioinformatics analyses of LAGE3 were based on The Cancer Genome Atlas, Gene Expression Omnibus, and Genomics of Drug Sensitivity in Cancer (GDSC) databases. We also performed RNA-sequencing on 78 paired samples from local PTC patients. RESULTS: We observed that LAGE3 was significantly up-regulated in most solid tumor types, including PTC compared with corresponding normal tissues. The high level of LAGE3 was also significantly associated with advanced malignancy. LAGE3 expression was significantly associated with cancer-related pathways, biochemical metabolism, and immune-related terms. Further, tumor microenvironment analysis indicated LAGE3 was positively correlated with different immune cells infiltrating levels and the activity of different steps of the cancer-immunity cycle. Analyses based on the GDSC database revealed that low levels of LAGE3 might be resistant to WZ3105, I-BET-762, and PHA-793887. In addition, the experimental results validated that knocking down LAGE3 could affect proliferation, migration, and invasion in the PTC cell lines. CONCLUSION: This study discloses that LAGE3 plays an oncogenic and cancer-immunological role, also providing novel PTC biological and clinical implications.

Genetic landscape of breast cancer and mutation tracking with circulating tumor DNA in Chinese women.

Considerable efforts have been devoted to exploring the breast cancer mutational landscape to understand its genetic complexity. However, no studies have yet comprehensively elucidated the molecular characterization of breast tumors in Chinese women. This study aimed to determine the potential clinical utility of peripheral blood assessment for circulating tumor-derived DNA (ctDNA) and comprehensively characterize the female Chinese population's genetic mutational spectrum. We used Omi-Seq to create cancer profiles of 273 patients enrolled at The First Affiliated Hospital of Wenzhou Medical University. The gene landscape results indicate PIK3CA and TP53 as the most frequently detected genes, followed by ERBB2, in Chinese breast cancer patients. The accuracy of ERBB2 copy number variations in tissue/formalin-fixed and paraffin-embedded samples was 95% with 86% sensitivity and 99% specificity. Moreover, mutation numbers varied between different molecular cell-free DNA subtypes, with the basal-like patients harboring a higher number of variants than the luminal patients. Furthermore, ratio changes in the max ctDNA allele fraction highly correlated with clinical response measurements, including cancer relapse and metastasis. Our data demonstrate that ctDNA characterization using the Omi-Seq platform can extend the capacity of personalized clinical cancer management.

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.

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.

[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.

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.

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.

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.

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.

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.

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.