PURPOSE:The aim of this study was to evaluate the correlation between central lymph node (CLN) metastasis and clinicopathologic characteristics of papillary thyroid cancer (PTC). In addition, we investigated the incidence and risk factors for contralateral CLN metastasis in unilateral PTC. This study suggests the appropriate surgical extent for CLN dissection.METHODS:A prospective study of 500 patients with PTC who underwent total thyroidectomy and prophylactic bilateral CLN dissection was conducted.RESULTS:Of 500 patients, 255 had CLN metastases. The rate of CLN metastasis was considerably higher in cases of younger patients (<45 years old) (P < 0.001; odds ratio [OR], 2.357) and of a maximal tumor size greater than 1 cm (P < 0.001; OR, 3.165). Ipsilateral CLN metastasis was detected in 83.1% of cases (133/160) of unilateral PTC, only contralateral CLN metastases in 3.7% of cases (6/160), and bilateral CLN metastases in 13.1% of cases (21/160). The rate of contralateral CLN metastasis was considerably higher in cases of PTC with a large tumor size (≥1 cm) (P = 0.019; OR, 4.440) and with ipsilateral CLN metastasis (P = 0.047; OR, 2.613).CONCLUSION:Younger age (<45 years old) and maximal tumor size greater than 1 cm were independent risk factors for CLN metastasis. Maximal tumor size greater than 1 cm and presence of ipsilateral CLN macrometastasis were independent risk factors for contralateral CLN metastasis. Therefore, both CLN dissections should be considered for unilateral PTC with a maximal tumor size greater than 1 cm or presence of ipsilateral CLN macrometastasis.

Purpose: Neoadjuvant chemotherapy (NC) is yet to be established as the definitive treatment regimen for locally advanced breast cancer (LABC). The aim of this study was to determine the efficacy and toxicity of NC with epirubicin and paclitaxel. Methods: Between March 2007 and January 2009, 50 patients with LABC were enrolled in an open-label, phase II, multicenter study carried out at five distinct institutions. All patients were scheduled to receive four cycles of 60 mg/m(2) epirubicin and 175 mg/m2 paclitaxel every 3 weeks, preoperatively, unless they developed profound side effects or disease progression. After curative surgery, two additional cycles of chemotherapy were administered to patients who had shown a positive response to NC. Results: In all, 196 cycles of chemotherapy were administered preoperatively; 47 of the 50 patients (94%) underwent all four cycles of designated treatment. Complete disappearance of invasive foci of the primary tumor, and negative axillary lymph nodes were confirmed in eight patients (16.0%), post operation. The cumulative 5-year disease-free survival rate was 70.0% for patients with complete remission (CR) and partial remission (PR), and 33.3% for patients with stable disease (SD) and progressive disease (PD) (p=0.018). The cumulative 5-year overall survival was 90.0% for patients who achieved CR and PR and 55.6% for patients who had SD and PD (p=0.001). Neutropenia (42.0%) was the most common grade 3/4 toxicity. However, none of the toxicities resulted in cessation of the treatment. Conclusion: The encouraging pathologic response observed in the patients treated with epirubicin plus paclitaxel NC in this study suggests that epirubicin could be a substitute for doxorubicin, which is the most cardiotoxic agent.

Medullary thyroid carcinoma and papillary thyroid carcinoma are different subtypes of thyroid carcinoma. The concomitant occurrence of medullary thyroid carcinoma and papillary thyroid carcinoma as a collision tumor is rare. We describe five cases of medullary and papillary thyroid carcinoma as a collision tumor. Four women and one man underwent thyroidectomy for treatment of thyroid cancer. Collision tumor was then detected by histopathologic finding. Genetic testing, point mutation of the BRAF gene or mutation of the RET gene was performed in three cases. However, only one case had point mutation of the BRAF gene. Exact diagnosis of this uncommon event is important because the strategies for treatment of papillary thyroid carcinoma and medullary thyroid carcinoma are different.

Aberrant DNA methylation occurs early and frequently in tumorigenesis. Identification of DNA methylation biomarkers is a field that provides potential for improving the clinical process of breast cancer diagnosis. We utilized a genome-wide technique, methylated DNA isolation assay (MeDIA), in combination with high-resolution CpG microarray analysis to identify hypermethylated genes in breast cancer. Among differentially methylated genes between tumor and adjacent normal tissues, 3 candidate genes (LHX2, WT1 and OTP) were finally selected through a step-wise filtering process and examined for methylation status in normal tissues, primary tumor, and paired adjacent normal-appearing tissues from 39 breast cancer patients. Based on the calculated cut-off values, all genes showed significantly higher frequencies of aberrant hypermethylation in primary tumors (43.6% for LHX2, 89.7% for WT1 and 100% for OTP, p<0.05) while frequencies were intermediate in paired adjacent normal tissues and absent in normal tissues. On further analysis, the methylation level in primary tumors was not significantly correlated with clinicopathological features. Interestingly, DNA methylation of a novel gene OTP was detected in adjacent normal tissues even 6 cm away from primary tumors, suggesting that OTP methylation may qualify as a biomarker for the early detection of breast cancer. In conclusion, we successfully identified a novel gene OTP frequently methylated in breast cancer by genome-wide screening. Our results suggest that the OTP gene may play a crucial role in breast carcinogenesis, although further clinical validation will be needed to evaluate the potential application of OTP in the early detection of breast cancer.

Purpose Poor cosmetic outcome have been reported as a result of breast cancer operation due to lower quadrant breast tumors; this is particularly true for women with small, firm breasts. Herein, we report here on the use of superior based lateral breast rotation flap reconstruction to improve cosmetic outcome in patients with lower quadrant breast cancer. Methods We enrolled 33 patients with invasive breast cancer located in the lower quadrant of the breast, which were located more than 2 cm apart from the nipple. After completing a quadrantectomy, a single S-shaped or reverse S-shaped incision was made from axilla to tumor site. Two triangular skin islands, one on the axilla and one overlying the tumor were marked for excision. Once the fibroglandular tissues and the additional fatty tissue of the lateral chest wall were appropriately mobilized, the breast defect was closed at the mid-point of the parenchymal thickness in order to keep the natural position of the infra mammary fold. Results Median tumor size was 2.3 cm (range, 0.7-3.5 cm) and median resected volume was 35.5 g (range, 27.0-51.0 g). With a mean follow-up of 24.5 months (range, 9.0-33.5 months), cosmetic outcomes were good (94.0%) to fair (6.0%) at 6 months after the procedure, and there was no local or systemic recurrence during the short term follow-up period. Conclusion Clearly, this type of rotation flap reconstruction is an oncologically safe and a cosmetically sound procedure. Hopefully this rotation flap reconstruction technique will become more widely available and perhaps a standard procedure for lower quadrant breast tumors, especially for cosmetic treatment of small to medium-sized breasts.

Fatty acid synthase (FASN) is a potential therapeutic target for treatment of cancer and obesity, and is highly elevated in 30% of HER2‐overexpressing breast cancers. Considerable interest has developed in searching for novel FASN inhibitors as therapeutic agents in treatment of HER2‐overexpressing breast cancers. Amentoflavone was found to be effective in suppressing FASN expression in HER2‐positive SKBR3 cells. Pharmacological inhibition of FASN by amentoflavone specifically down‐regulated HER2 protein and mRNA, and caused an up‐regulation of PEA3, a transcriptional repressor of HER2. In addition, pharmacological blockade of FASN by amentoflavone preferentially decreased cell viability and induced cell death in SKBR3 cells. Palmitate reduced the cytotoxic effect of amentoflavone, as the percentage of viable cells was increased after the addition of exogenous palmitate. Amentoflavone‐induced FASN inhibition inhibited the translocation of SREBP‐1 in SKBR3 cells. Amentoflavone inhibited phosphorylation of AKT, mTOR, and JNK. The use of pharmacological inhibitors revealed that the modulation of AKT, mTOR, and JNK phosphorylation required synergistic amentoflavone‐induced FASN inhibition and HER2 activation in SKBR3 cells. These results suggest that amentoflavone modulated FASN expression by regulation of HER2‐pathways, and induced cell death to enhance chemopreventive or chemotherapeutic activity in HER2‐positive breast cancers. Copyright © 2012 John Wiley & Sons, Ltd.

Background : Neoadjuvant chemotherapy has become a standard therapy for patients with locally advanced breast cancer. Recently, new regimens of breast cancer chemotherapy containing taxanges further improve survival compared with standard chemotherapy regimens, but taxanes are toxic, expensive, and might benefit only a few patient. Howeve, predictive factors in breast cancer treated with neoadjuvant chemotherapy differ from those of early breast cancer. The purpose of this study was to identify the clinical significance of potential predictive factors in breast cancer patients treated by neoadjuvant chemotherapy. Methods : A total of 112 stage Ⅱ and Ⅲ breast cancer patients received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this study. We examined the clinical and biological factors by immunohistochemistry. We analyzed clinical outcome and their correlation with clinicopathologic parameters. Results : A total of 112 patients with a median age of 45.9 were evaluated in this study. The overall clinical response rate (RR) was 80(71.5%) including 5(4.5%) complete response and 75(67.0%) partial response. Consequently, 12 (10%) patients achieved pCR. Among the traditional clinicopathologic parameters (age, stage, histologic grade, ER, PR, c-erbB2, p53 and Ki-67) investigated, none of the marker was correlated with response rate(RR). However, pCR was correlated with initial tumor stage (p=0.04), triple negative(p=.002), p53(p=.011), Ki-67(p=.015). Conclusions : Several molecular markers provided useful predictive information in locally advanced breast cancer patients treated with neoadjuvant chemotherapy. Triple negative phenotype, p53 high expression and Ki-67 high expression was associated with a higher pCR to neoadjuvant docetaxel/doxorubicin chemotherapy.

Purpose The purpose of this study is to evaluate imaging and histopathologic findings including the immunohistochemical characteristics of invasive micropapillary carcinoma (IMPC) of the breast. Methods Twenty-nine patients diagnosed with IMPC were included in the present study. Mammographic, sonographic, and magnetic resonance imaging (MRI) findings were analyzed retrospectively according to the American College of Radiology Breast Imaging Reporting and Data System lexicon. 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) findings were also evaluated. Microscopic slides of surgical specimens were reviewed in consensus by two pathologists with a specialty in breast pathology. Results Most IMPCs presented as a high density irregular mass with a non-circumscribed margin associated with microcalcifications on mammography, as an irregular hypoechoic mass with a spiculated margin on ultrasound, and as irregular spiculated masses with washout patterns on MRI. PET-CT showed a high maximum standardized uptake value (SUVmax) (mean, 11.2). Axillary nodal metastases were identified in 65.5% of the patients. Immunohistochemical studies showed high positivities for estrogen receptor and c-erbB-2 (93.1% and 51.7µ, respectively). Conclusion Even though the imaging characteristics of IMPCs are not distinguishable from typical invasive ductal carcinomas, this tumor type frequently results in nodal metastases and high positivities for both estrogen receptor and c-erbB-2. The high SUVmax value that is apparent on PET-CT might be helpful in the diagnosis of IMPC.

AMP-activated protein kinase (AMPK) is a sensor of cellular energy status found in all eukaryotes. Recent studies indicate that AMPK activation strongly suppresses cell proliferation in tumor cells, which requires high rates of protein synthesis and de novo fatty acid synthesis for their rapid growth. Pomolic acid (PA) has been previously described as being active in inhibiting the growth of cancer cells. In this study, we investigated PA activated AMPK, and this activity was related to proliferation and apoptosis in MCF7 breast cancer cells. PA inhibited cell proliferation and induced sub-G(1) arrest, elevating the mRNA levels of the apoptotic genes p53 and p21. PA activated caspase-3, -9, and poly(ADP-ribose) polymerase, and this effect was inhibited by z-VAD-fmk. AMPK activation was increased by treating cells with PA, inactivated by treating cells with a compound C, and co-treatment consisting of PA and aminoimidazole carboxamide ribonucleotide (AICAR) synergistically activated AMPK. These anti-cancer potentials of PA were accompanied by effects on de novo fatty acid synthesis as shown by the decreased expression of fatty acid synthase, and decreased acetyl-CoA carboxylase activation and incorporation of [(3)H]acetyl-CoA into fatty acids. In addition, PA inhibited key enzymes involved in protein synthesis such as mammalian target of rapamycin (mTOR), 70 kDa ribosomal protein S6 kinase (p70S6K), and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1). These results suggest that PA exerts anti-cancer properties through the modulation of AMPK pathways and its value as an anti-cancer agent in breast cancer therapy.

Paraffin oil injection into the breast, which had been used for breast augmentation in the past, can cause various complications. Complete removal of paraffinoma lesions with immediate breast reconstruction using autogenous tissue is a very satisfactory treatment option. However, diffuse random distribution of paraffin oil through the subdermal layer makes it impossible to remove all of the lesions with overlying skin without resulting in a shortage of available skin and poor cosmesis. We herein report the case of a patient with breast cancer associated with paraffinoma, treated with skin-sparing mastectomy and axillary node dissection with immediate extended latissimus dorsi flap reconstruction, resulting in good cosmetic outcome, and showing no complications during the wound-healing process.

Purpose: Phyllodes tumors (PTs) of the breast have been classified as benign, borderline, or malignant based on their histopathologic features. However, predicting clinical behavior based on these features has proven to be difficult given that local recurrence occurs in both benign and malignant PTs. Recurrence has been shown to mirror the histologic pattern of the primary tumor or to show dedifferentiation. The aim of this study was to assess the value of the histopathologic parameters, expression or mutation of c-Kit and platelet derived growth factor receptor alpha (PDGFRA) in predicting tumor recurrence. Methods: Representative areas from 39 benign, 16 borderline, and 12 malignant PTs were selected for construction of tissue microarrays. Immunohistochemical analyses for p53, Ki-67, c-Kit, and PDGFRA were performed and SSCP-PCR analysis was carried out to identify mutations in exons 9, 11, 13, and 17 of the c-Kit gene and exons 12 and 18 of the PDGFRA gene. Clinicopathologic features, including tumor recurrence and margin status, were also evaluated. Results: Of the 67 PTs, 11 cases (16.4%) recurred from 3 to 92 months following initial diagnosis (4 benign, 2 borderline, and 5 malignant). One benign PT case recurred as a borderline tumor and two borderline PT cases recurred as malignancies. Three patients died of malignant PT. No mutations of the c-Kit or PDGFRA genes were found and there was no statistically significant association of either p53 or p16 immunostaining with recurrent disease (p>0.05). However, histologic grade (p=0.033), margin status (p< 0.001), Ki-67 (p=0.012), c-Kit (p=0.002), and PDGFRA (p= 0.007) stromal immunopositivity were significantly correlated with recurrence. Conclusion: Even though positive or close margins were significantly associated with tumor recurrence, stromal c-Kit, PDGFRA positivity, and the Ki-67 index were useful for predicting recurrent PTs. Despite this, no c-Kit or PDGFRA mutations were found.

Evaluate the effect of different concentrations of growth hormone (GH) on the in vitro development of domestic dog (Canis lupus familiaris) preantral follicles in the presence or absence of follicle stimulating hormone (FSH).Secondary preantral follicles, isolated by microdissection, were cultured in a medium composed of αMEM with bovine serum albumin (BSA), glutamine, hypoxanthine, insulin, transferrin, selenium and ascorbic acid (αMEM+-control) added at different concentrations of GH (GH10 ng/ml or GH50 ng/ml) and FSH (GH10 + FSH, GH50 + FSH). Follicle development was evaluated based on the percentage of intact follicles, antrum formation, follicular diameter, follicular viability using fluorescent markers and estradiol production.GH50 was the only treatment that maintained the same percentage of normal morphologically follicles from day 0 to day 18 of culture (P < 0.05). For all treatments, except the control, follicles were viable throughout the 18 days of culture (P < 0.05). GH50 supplemented with FSH (GH50 + FSH) resulted in the highest average follicular diameter (P < 0.05) from day 12 to 18. Follicles from both the control and the GH50 + FSH treatment groups actively and increasingly secreted estradiol from day 6 to 18 of culture (P < 0.05).Our study demonstrates that GH benefits the maintenance of follicular morphology in a dose-dependent manner and, in association with FSH, stimulates in vitro follicular growth and estradiol production.