Jeoung Won Bae

Prognostic Implications of MicroRNA-21 Overexpression in Invasive Ductal Carcinomas of the Breast

Purpose Among more than 500 microRNAs, microRNA-21 (miR-21) is known to act as an oncogene. The aim of this study was to investigate the significance of miR-21 expression level in relation with clinicopathological factors and prognosis in breast cancer. Methods MicroRNA was extracted from cancer and normal breast tissue of 109 breast cancer patients who underwent surgery from 2002 to 2004 using the Taqman® MicroRNA Assay. The correlation between miR-21 expression and clinicopathologic features was analyzed and the significance of miR-21 as a prognostic factor and its relationship with survival was determined. Results MiR-21 expression was higher in cancer tissues than in normal tissues (p<0.0001). High miR-21 expression was associated with mastectomy, larger tumor size, higher stage, higher grade, estrogen receptor (ER) negative, human epidermal growth factor receptor 2 (HER2) positive, HER2 positive breast cancer subtype, high Ki-67 expression, and death. On multivariate analysis, prognostic factors for overall survival were ER and miR-21. High miR-21 expression was significantly related to lower overall survival (p=0.031). Conclusion This study supports the role of miR-21 as an oncogene and a biomarker for breast cancer with its high expression in cancer tissues and its relationship with other prognostic factors and survival.

A Significant Correlation between Nuclear CXCR4 Expression and Axillary Lymph Node Metastasis in Hormonal Receptor Negative Breast Cancer

In breast cancer, the expression pattern of CXCR4 may be correlated with the degree of axillary lymph node involvement. The aim of this study was to evaluate the contributing factors that contribute to the correlation between CXCR4 expression and axillary lymph node metastasis in breast cancer. Between August 1997 and August 2002, sections of paraffin-embedded tissue were obtained from 107 patients who received optimal treatment for breast cancer. The expression of CXCR4 was evaluated by immunohistochemical staining. A significant correlation was found in the expression of nuclear CXCR4 and lymph node metastasis (P = 0.03). We found a significant correlation between a high nuclear expression of CXCR4 and axillary lymphatic metastasis in estrogen and progesterone receptor negative breast cancer (P = 0.01 and P = 0.01). There was a significant correlation between the high expression of nuclear CXCR4 and axillary lymphatic metastasis in comparisons between positive estrogen and/or progesterone receptor expression and negative expression (P = 0.02). Our results showed that high expression of nuclear CXCR4 was significantly correlated with lymph node metastasis in breast cancer. The high expression of nuclear CXCR4 in hormone receptor negative breast cancer was associated with a high possibility of lymph node metastasis.

Sonographic evaluation of breast nodules: comparison of conventional, real-time compound, and pulse-inversion harmonic images.

Objective To compare the use of conventional, real-time compound, and pulse-inversion harmonic imaging in the evaluation of breast nodules. Materials and Methods Fifty-two breast nodules were included in this study, conducted between May and December 2000, in which conventional, real-time compound, and pulse-inversion harmonic images were obtained in the same plane. Three radiologists, each blinded to the interpretations of the other two, evaluated the findings, characterizing the lesions and ranking the three techniques from grade 1, the worst, to grade 3, the best. Lesion conspicuity was assessed, and lesions were also characterized in terms of their margin, clarity of internal echotexture, and clarity of posterior echo pattern. The three techniques were compared using Friedmans test, and interobserver agreement in image interpretation was assessed by means of the intraclass correlation coefficient. Results With regard to lesion conspicuity, margin, and internal echotexture of the nodules, real-time compound imaging was the best technique (p < 0.05); in terms of posterior echo pattern, the best was pulse-inversion harmonic imaging (p < 0.05). Real-time compound and pulse inversion harmonic imaging were better than conventional sonography in all evaluative aspects. Interobserver agreement was greater than moderate. Conclusion Real-time compound and pulse-inversion harmonic imaging procedures are superior to conventional sonography in terms of both lesion conspicuity and the further characterization of breast nodules. Real-time compound imaging is the best technique for evaluation of the margin and internal echotexture of nodules, while pulse-inversion harmonic imaging is very effective for the evaluation of the posterior echo patterns.

Comparison of robotic adrenalectomy with traditional laparoscopic adrenalectomy with a lateral transperitoneal approach: a single-surgeon experience

Although several recent studies have demonstrated the feasibility and safety of robotic adrenalectomy, it is unknown whether this procedure has advantages over the traditional laparoscopic approach. This study compared our initial experience using the da Vinci‐S® robotic surgical system during laparoscopic adrenalectomy with our experience with traditional laparoscopic adrenalectomy.

Robotic thyroidectomy using bilateral axillo-breast approach: Comparison of surgical results with open conventional thyroidectomy.

The aim of the present study was to compare the surgical outcomes of robotic thyroidectomy using the bilateral axillo‐breast approach (BABA) with open conventional thyroidectomy.

Clinicopathological, immunohistochemical factors and recurrence associated with extrathyroidal extension in papillary thyroid microcarcinoma

BACKGROUND AND AIMS Extrathyroidal extension (ETE) is one of the most important factors correlated to poor outcome of papillary thyroid carcinoma (PTC). However, the role of ETE in the prognosis of papillary thyroid microcarcinoma (PTMC) and the factor associated with ETE of PTMC are unclear. We investigated clinicopathological, immunohistochemical factors associated with ETE of PTMC to identify whether PTMC with ETE would have more adverse prognostic factors and higher risk for recurrence. SETTING AND DESIGN We enrolled patients performed thyroidectomy due to PTC between January 2003 and June 2008 and selected patients diagnosed with PTMC among them. We investigated numerous clinicopathological, immunohistochemical factors of selected patients. MATERIALS AND METHODS Data from 325 patients diagnosed with conventional PTMC by intraoperative frozen section and final pathology were recorded retrospectively. STATISTICAL ANALYSIS USED A χ² test or an independent two-sample t-test, multiple logistic regression analysis, the Kaplan-Meier method, and log-rank test. RESULTS Thirty-four percent of patients (325 of 952) had PTMC on final pathology. Among them, the number of patients with and without ETE was 91 and 234, respectively. On both univariate and multivariate analysis; ETE of PTMC correlated with size (P < 0.001); tumor, node, and metastasis (TNM) staging (P = 0.001); multifocality (P = 0.001); lymph node metastasis (P < 0.001); radioactive iodine (RAI) therapy (P = 0.001); and recurrence (P = 0.037). CONCLUSIONS ETE of conventional PTMC is associated with size, multifocality, lymph node metastasis, and recurrence. More extensive surgery should be considered for patients having ETE identified by intraoperative frozen sections, preoperative imaging, and intraoperative finding and other high risk factors.

Circulating Tumor Cells Detected by RT-PCR for CK-20 before Surgery Indicate Worse Prognostic Impact in Triple-Negative and HER2 Subtype Breast Cancer.

Purpose Circulating tumor cells (CTC) clearly correlate with unfavorable outcomes for patients with metastatic breast cancer, but the long-term prognostic implications of CTC for molecular subtypes of operable breast cancer are not yet known. We explored the relationships between previously established prognostic factors and CTC in operable breast cancer, and the significance of CTC by breast cancer molecular subtype. Methods We retrospectively evaluated 166 patients with operable breast cancer (stage I-IIIA) diagnosed from April 1997 to May 2003. CTC were detected using cytokeratin-20 (CK-20) mRNA expression in peripheral blood samples that were collected just prior to surgery under general anesthesia. Clinicopathological characteristics of the cancer were analyzed according to CTC status. Metastasis-free survival (MFS) and overall survival (OS) were analyzed according to CTC status and breast cancer molecular subtype. Results CK-20 mRNA-positive CTC was detected in 37 of 166 patients (22.3%) and was not correlated with any previous clinical factors in univariate analysis (p>0.05). After a median follow-up of 100 months, the patients with CK-20 mRNA-positive CTC had less favorable outcomes in terms of MFS and OS than those without detectable CTC (log-rank p<0.05). Among molecular subtypes of operable breast cancer, the patients with CK-20 mRNA-positive CTC had shorter MFS and OS in triple negative and human epidermal growth factor 2 (HER2) breast cancer subtype (log-rank, p<0.05). Conclusion CK-20 mRNA-positive CTC may lend insight into tumor progression as a prognostic indicator especially in the triple negative and HER2 subtypes of operable breast cancer.

Toxicities, dose reduction and delay of docetaxel and paclitaxel chemotherapy in breast cancer without distant metastases.

BACKGROUND Docetaxel and paclitaxel are likely to have different toxicity profiles, dose reduction and delays despite their similar medical results in breast cancer patients. AIMS This study examined retrospectively the incidence and severity of certain toxicities, dose reduction and delay of two taxanes. MATERIALS AND METHODS From January 2009 to June 2010, the incidence and severity of toxicities as well as the dose reduction, dose delay, granulocyte colony stimulating factor (G-CSF) in 54 patients with operable lymph node-positive (tumor stage T1, T2, or T3 and nodal stage N1 or N2) and high risk, node-negative (T2 or T3, N0) breast cancer without a distant metastases who received adjuvant chemotherapy - adriamycin, cyclophosphamide, docetaxel (TAC) and adriamycin, cyclophosphamide, paclitaxel (ACP)- were evaluated. STATISTICAL ANALYSIS USED Mann-Whitney test and Fishers exact test. RESULTS AND CONCLUSION The patients in the ACP group experienced more frequent peripheral neuropathy (P=0.025), nausea (P=0.033) than those in the TAC group. Febrile neutropenia was significant in TAC (P=0.001). Increasing age was associated with an increased risk of anemia (P=0.004), fatigue (P=0.009) and pain (P=0.003), and a decreasing body mass index was associated with an increased risk of febrile neutropenia (P=0.009). Dose reduction and delay occurred due to febrile neutropenia and an increase in aspartate aminotransferase (AST)/alanine aminotransferase (ALT). The dose reduction was only significant in the TAC group (P= 0.001). A taxane-based regimen should be chosen for breast cancer patients based on the pharmacokinetics, dosing schedule, clinical activity and toxicity profile that best meet the patients therapeutic needs and quality of life.

D2-40, Podoplanin, and CD31 as a Prognostic Predictor in Invasive Ductal Carcinomas of the Breast.

Purpose Distant metastasis and recurrence are major prognostic factors associated with breast cancer. Both lymphovascular invasion (LVI) and blood vessel invasion (BVI) are important routes for metastasis to regional lymph nodes and for systemic metastasis. Despite the importance of vascular invasion as a prognostic factor, application of vascular invasion as a histopathological criterion is controversial. The aim of this study was to distinguish LVI from BVI in prognosis and recurrence of breast cancer using an endothelial subtype specific immunohistochemical stain (podoplanin, D2-40, and CD31). Methods Sections from 80 paraffin-embedded archival specimens of invasive breast cancer were stained for podoplanin, D2-40, or CD31 expression. Immunohistochemical staining results were correlated with clinicopathological features, such as tumor size, status of lymph node metastases, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor-2 expression, and recurrence. Patients with ductal carcinoma in situ and stage IV breast cancer were excluded. Results A significant correlation was found between D2-40 LVI positivity and lymph node metastasis (p=0.022). We found a significant correlation between D2-40 LVI positivity and recurrence of breast cancer (p=0.014). However, no significant correlation was found between BVI and recurrence. A poorer disease free survival was shown for D2-40 positive LVI (p=0.003). In a multivariate analysis, the presence of D2-40 LVI positivity revealed a significant association with decreased disease-free survival. Conclusion D2-40 LVI positivity was a more prognostic predictor of breast cancer than BVI.

Role of secreted type I collagen derived from stromal cells in two breast cancer cell lines

Collagen is one of numerous components of the cellular microenvironment. To date, the association between the microenvironment and tumorigenesis of malignant breast cancer remains elusive. Therefore, the aim of the present study was to investigate the potential role of a secretory protein of stromal cells, type I collagen, in the development of the aggressive characteristics of breast cancer cells. MDA-MB231 and MCF7 breast cancer cell lines were maintained in cultured media of normal human dermal fibroblasts (HDFs) and type I collagen-containing media. The morphological changes, adhesion capacity and matrix metalloproteinase (MMP)-1, -2 and -9 mRNA levels were evaluated. The results revealed that cell sprouting and adhesion capacity were enhanced in the MCF7 and MDA-MB231 breast cancer cells in HDF-conditioned culture media as well as in response to type I collagen treatment. The expression of MMP-9 mRNA was high in breast cancer cells cultured with the media of normal HDFs, compared with that of the control media. These data indicate that type I collagen, which is secreted by stromal fibroblasts, may augment the aggressive characteristics of breast cancer cells through the induction of MMP-9 mRNA.