Fibrosarcomatous Transformation in Dermatofibrosarcoma Protuberans of the Male Breast and its Association with Magnetic Resonance Imaging and Immunohistopathologic Features.

BACKGROUND: Dermatofibrosarcoma Protuberans (DFSP) is a rare soft tissue sarcoma, accounting for approximately 1% of all tumors; however, DFSP of the breast is extremely rare. Moreover, DFSP generally has a low malignant potential and is characterized by a high rate of local recurrence along with a small but definite risk of metastasis. The risk of metastasis is higher in fibrosarcomatous transformation in DFSP than in ordinary DFSP. CASE REPORT: We have, herein, reported a case of a 61-year-old male patient with fibrosarcomatous transformation in DFSP. Preoperative Dynamic Contrastenhanced Magnetic Resonance Imaging (DCE-MRI) of the breast revealed an oval-shaped mass with heterogeneous internal enhancement, a large vessel embedded within, and a washout curve pattern on kinetic curve analysis. The mass exhibited a hyperintense signal on Diffusion-weighted Imaging (DWI), with a low apparent diffusion coefficient value. Histologically, the bland spindle tumor cells were arranged in a storiform pattern. Areas with the highest histological grade demonstrated increased cellularity, cytological atypia, and mitotic activity. Immunohistochemically, Ki-67 and p53 were highly expressed. CONCLUSION: Recognizing the risk and accurately diagnosing fibrosarcomatous transformation in male breast DFSP are critical for improving prognosis and establishing appropriate treatment and follow-up plans. This emphasizes the significance of combining immunohistopathological features with DCE-MRI and DWI to assist clinicians in the early and accurate diagnosis of sarcomas arising from male breast DFSP.

Incidence and risk factors of breast cancer-related lymphedema in Korea: a nationwide retrospective cohort study.

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a secondary lymphedema that occurs after breast cancer related treatments. BCRL develops from damage or dysfunction of the normally functioning lymphatic system due to surgery, radiation therapy, and rarely due to cancer recurrence. This nationwide, retrospective study was aimed at investigating the incidence and risk factors of BCRL using the database of the Korean National Health Insurance Service (NHIS). METHODS: Patients with newly diagnosed breast cancer who underwent breast surgery from 1 January 2017 to 31 December 2020, were recruited. The incidence was compared by four groups according to the operation type of breast cancer [breast conserving surgery (BCS) with sentinel lymph node biopsy (S), BCS with axillary lymph node dissection (A), total mastectomy (TM) with S, modified radical mastectomy (MRM)]. The incidence rates of lymphedema were calculated by the number of incident events by the total follow-up period. Cox proportional hazard regression was used to calculate the risk of incidence of lymphedema based on a patients' characteristics, breast cancer treatment, and comorbidities. RESULTS: The final cohort of operation subjects that satisfied the inclusion criteria was 34 676. BCRL occurred in 4242 patients (12.2%), and the median follow-up period was 695.4 days. The BCRL was diagnosed in the BCS with S (8.0%), BCS with A (23.5%), TM with S (10.7%), and MRM (28.5%) with an incidence of 40.8, 132.2, 55.8, and 171.8 per 1000 person-years, respectively. Young age, obesity, chemotherapy, radiotherapy, residence in metropolitan areas, and hyperlipidemia were identified as risk factors. CONCLUSION: In Korea, the incidence of BCRL was found to be 12.2%, with the highest risk observed among patients who underwent MRM. Therefore, surgical oncologists should meticulously assess the appropriate surgical approach and consider providing education to patients with risk factors for BCRL, aiming to ensure effective prevention strategies.

Fisetin Inhibits UVA-Induced Expression of MMP-1 and MMP-3 through the NOX/ROS/MAPK Pathway in Human Dermal Fibroblasts and Human Epidermal Keratinocytes.

Fisetin is a flavonoid found in plants and has been reported to be effective in various human diseases. However, the effective mechanisms of ultraviolet-A (UVA)-mediated skin damage are not yet clear. In this study, we investigated the protective mechanisms of fisetin regarding UVA-induced human dermal fibroblasts (HDFs) and human epidermal keratinocytes (HEKs) damages. Fisetin showed a cytoprotective effect against UVA irradiation and suppressed matrix metalloproteinases (MMPs), MMP-1, and MMP-3 expression. In addition, fisetin was rescued, which decreased mRNA levels of pro-inflammatory cytokines, reactive oxygen species production, and the downregulation of MAPK/AP-1 related protein and NADPH oxidase (NOX) mRNA levels. Furthermore, UVA-induced MMP-1 and MMP-3 were effectively inhibited by siRNAs to NOX 1 to 5 in HDFs and HEKs. These results indicate that fisetin suppresses UVA-induced damage through the NOX/ROS/MAPK pathway in HDFs and HEKs.

The prognosis of NX stage in patients with pT1 papillary thyroid cancer who underwent lobectomy.

Lymph node (LN) metastasis is known to impact the prognosis of patients with well-differentiated thyroid cancer. Herein, we aimed to determine the effect of NX stage on the prognosis of patients with papillary thyroid cancer who underwent thyroid lobectomy. We initially selected 1257 patients who underwent thyroid cancer surgery from 2012 to 2015. Of the 1257 patients, we included 556 in the analysis, excluding patients diagnosed with other types of thyroid cancer, those who underwent total or completion thyroidectomy, and those diagnosed with LN metastasis prior to surgery. The median follow-up time was 61.8 months (range: 12.3-108.9 months). After dividing the patients into N0, N1, and NX stage groups, we performed univariate and multivariate analyses. The 5-year recurrence-free survival (RFS) was analyzed using R version 3.2.5. The mean patient age was 45.0 ± 10.9 years. Of the 556 patients, 336 patients (60.4%) were diagnosed with N0 stage, 134 (24.1%) were N1 stage, and 86 (15.5%) were NX stage. Univariate and multivariate analyses were performed to identify prognostic factors for RFS. Considering gender, age, tumor size, surgery types, extrathyroidal extension, multifocality, and recurrence, no statistically significant differences were noted between the 3 groups. The 5-year RFS rates were 98.8%, 95.5%, and 97.6% for N0, N1, and NX groups, respectively, without significant differences between the 3 groups (P = .56). Considering the T1b stage, the 5-year RFS rates were 100%, 93.1%, and 93.7% in the N0, N1, and NX groups, respectively, with a statistically significant difference between the 3 groups (P = .018). Accordingly, the NX status cannot be deemed a prognostic factor for RFS in patients with papillary thyroid cancer who underwent thyroid lobectomy. However, the benefit of prophylactic central-LN dissection should be considered in patients with well-differentiated thyroid cancer diagnosed with T1b stage.

Aurora kinase A induces migration and invasion by inducing epithelial-to-mesenchymal transition in colon cancer cells.

Aurora kinase is a family of serine/threonine kinases intimately associated with mitotic progression and the development of human cancers. Studies have shown that aurora kinases are important for the protein kinase C (PKC)-induced invasion of colon cancer cells. Recent studies have shown that aurora kinase A promotes distant metastasis by inducing epithelial-to-mesenchymal transition (EMT) in colon cancer cells. However, the role of aurora kinase A in colon cancer metastasis remains unclear. In this study, we investigated the effects of aurora kinase A on PKC-induced cell invasion, migration, and EMT in human SW480 colon cancer cells. Treatment with 12-O-tetradecanoylphorbol- 13-acetate (TPA) changed the expression levels of EMT markers, increasing α-SMA, vimentin, and MMP-9 expression and decreasing E-cadherin expression, with changes in cell morphology. TPA treatment induced EMT in a PKC-dependent manner. Moreover, the inhibition of aurora kinase A by siRNAs and inhibitors (reversine and VX-680) suppressed TPA-induced cell invasion, migration, and EMT in SW480 human colon cells. Inhibition of aurora kinase A blocked TPA-induced vimentin and MMP-9 expression, and decreased E-cadherin expression. Furthermore, the knockdown of aurora kinase A decreased the transcriptional activity of NF-κB and AP-1 in PKC-stimulated SW480 cells. These findings indicate that aurora kinase A induces migration and invasion by inducing EMT in SW480 colon cancer cells. To the best of our knowledge, this is the first study that showed aurora kinase A is a key molecule in PKC-induced metastasis in colon cancer cells. [BMB Reports 2022;55(2): 87-91].

Downregulation of matriptase suppresses the PAR­2/PLCγ2/PKC­mediated invasion and migration abilities of MCF­7 breast cancer cells.

Matriptases, members of the type II transmembrane serine protease family, are cell surface proteolytic enzymes that mediate tumor invasion and metastasis. Matriptase is highly expressed in breast cancer and is associated with poor patient outcome. However, the cellular mechanism by which matriptase mediates breast cancer invasion remains unknown. The present study aimed to determine the role of matriptase in the protein kinase C (PKC)­mediated metastasis of MCF­7 human breast cancer cells. Matriptase small interfering RNA­mediated knockdown significantly attenuated the 12­O­tetradecanoylphorbol­13­acetate (TPA)­induced invasiveness and migration of MCF­7 cells, and inhibited the activation of phospholipase C γ2 (PLCγ2)/PKC/MAPK signaling pathways. Matriptase­knockdown also suppressed the expression of MMP­9 and inhibited the activation of NF­κB/activator protein­1 in MCF­7 cells. Additionally, GB83 [an inhibitor of protease­activated receptor­2 (PAR­2)] inhibited PKC­mediated MMP­9 expression and metastatic ability in MCF­7 cells. Furthermore, downregulation of matriptase suppressed TPA­induced MMP­9 expression and invasiveness via PAR­2/PLCγ2/PKC/MAPK activation. These findings shed light on the mechanism underlying the role of matriptase in MCF­7 cell invasion and migration ability, and suggest that matriptase modulation could be a promising therapeutic strategy for preventing breast cancer metastasis.

Breast Cancer Statistics in Korea, 2018.

Breast cancer is the most common malignancy in Korean women, and its incidence continues to increase. The Korean Breast Cancer Society (KBCS) established a nationwide breast cancer database through its online enrollment program in 1996. This study aimed to analyze the clinical characteristics of breast cancer in Korea, and to assess the pattern of changes in breast cancer management in 2018. We analyzed the KBCS and Korea Central Cancer Registry (KCCR) databases in 2018. In 2018, 28,157 patients were newly diagnosed with breast cancer, of whom 4,510 had noninvasive breast cancer and 23,647 had invasive breast cancer. The age-standardized rate of breast cancer in 2018 was 79.0 per 100,000 women (65.6 invasive, 13.4 noninvasive). The median age of female patients diagnosed with breast cancer in 2018 was 52 years, and the incidence of breast cancer was the highest in the 40-49-years age group (9,432 patients, 33.6%). The proportion of patients with stage 0 and stage I breast cancer continued to increase, accounting for 63.8% of cases, and breast-conserving surgery was performed more often than mastectomy (66.2% vs. 33.0%). The most common subtypes of breast cancer were hormone receptor [HR]-positive and human epidermal growth factor receptor-2 (HER2)-negative types (65.9% of cases), while the HR-negative and HER2-positive types accounted for 9.2% of cases. According to the KCCR data, from 2014 to 2018, the 5-year relative survival rate of patients with breast cancer was 93.3%, which was 14.0% higher than that from 1993 to 1995 (79.3%). The clinical characteristics of breast cancer in Korea have been changing, and national databases can improve our understanding of the disease characteristics of Korean women. Therefore, updating the KBCS registry is important for the effective management of breast cancer in Korea.

Bruton's agammaglobulinemia tyrosine kinase (Btk) regulates TPA­induced breast cancer cell invasion via PLCγ2/PKCß/NF­κB/AP­1­dependent matrix metalloproteinase­9 activation.

Bruton's agammaglobulinemia tyrosine kinase (BTK) is an important cytoplasmic tyrosine kinase involved in B­lymphocyte development, differentiation, and signaling. Activated protein kinase C (PKC), in turn, induces the activation of mitogen­activated protein kinase (MAPK) signaling, which promotes cell proliferation, viability, apoptosis, and metastasis. This effect is associated with nuclear factor­κB (NF­κB) activation, suggesting an anti­metastatic effect of BTK inhibitors on MCF­7 cells that leads to the downregulation of matrix metalloproteinase (MMP)­9 expression. However, the effect of BTK on breast cancer metastasis is unknown. In this study, the anti­metastatic activity of BTK inhibitors was examined in MCF­7 cells focusing on MMP­9 expression in 12­O­tetradecanoylphorbol­13­acetate (TPA)­stimulated MCF­7 cells. The expression and activity of MMP­9 in MCF­7 cells were investigated using quantitative polymerase chain reaction analysis, western blotting, and zymography. Cell invasion and migration were investigated using the Matrigel invasion and cell migration assays. BTK inhibitors [ibrutinib (10 µM), CNX­774 (10 µM)] significantly attenuated TPA­induced cell invasion and migration in MCF­7 cells and inhibited the activation of the phospholipase Cγ2/PKCß signaling pathways. In addition, small interfering RNA specific for BTK suppressed MMP­9 expression and cell metastasis. Collectively, results of the present study indicated that BTK suppressed TPA­induced MMP­9 expression and cell invasion/migration by activating the MAPK or IκB kinase/NF­κB/activator protein­1 pathway. The results clarify the mechanism of action of BTK in cancer cell metastasis by regulating MMP­9 expression in MCF­7 cells.

Hyperglycemia during Adjuvant Chemotherapy as a Prognostic Factor in Breast Cancer Patients without Diabetes.

PURPOSE: Breast cancer treatments, including chemotherapy, administered in combination with glucocorticoids can induce hyperglycemia. This study aimed to investigate the effect of hyperglycemia during adjuvant chemotherapy on the prognosis of breast cancer patients without a known history of diabetes. METHODS: In this study, 936 patients who underwent breast cancer surgery from 2010 to 2015 were initially selected as participants. Chemotherapy-related hyperglycemia was defined as fasting plasma glucose levels ≥ 100 mg/dL or random blood glucose levels ≥ 140 mg/dL during 2 or more cycles of adjuvant chemotherapy. After dividing the patients into the euglycemia and hyperglycemia groups, univariate and multivariate analyses were performed, and survival outcomes were analyzed by propensity score matching. RESULTS: The mean age of the patients was 47.4 ± 7.7 years, and the median follow-up period was 70.1 months. Eighty-two patients (19.4%) were diagnosed as having hyperglycemia. There were significant differences between the euglycemia and hyperglycemia groups with respect to age, hypertension, body mass index, axillary surgery extents, nodal stage, and total steroid dosage. T stage, vascular invasion, and hyperglycemia were identified as prognostic factors of relapse-free survival (RFS). The 5-year RFS rates were 92.0% and 82.3% in the euglycemia and hyperglycemia groups, respectively, and there was a statistically significant difference between the 2 groups (p = 0.011). The 5-year overall survival rates were 94.6% and 92.0% in the euglycemia and hyperglycemia groups, respectively, showing no statistically significant difference between the 2 groups (p = 0.113). CONCLUSION: These data suggest that hyperglycemia during adjuvant chemotherapy is a prognostic factor for RFS in breast cancer patients without diabetes.

Breast Cancer Statistics in Korea in 2017: Data from a Breast Cancer Registry.

This article describes the breast cancer statistics in Korea, including the incidence, type of surgical procedure, stage, and molecular subtype, using the Korean Breast Cancer Society (KBCS) and Korea Central Cancer Registry data. There were a total of 26,534 new breast cancer diagnoses in 2017 in Korea, of which 4,139 were carcinoma in situ cases and 22,395 were invasive cancer cases. The age standardized rate of breast cancer was 75.3 per 100,000 women in 2017 (63.0 of invasive carcinoma and 12.3 of carcinoma in situ), and it has been steadily increasing across all age groups. Breast cancer occurred most commonly in the 40-49 age group. Compared to 2016, breast conserving surgery (BCS) has increased, and 67.4% of patients were treated with BCS in 2017. The proportions of stage 0 and stage I have continued to increase, accounting for 60.7%. The most common subtype of breast cancer was hormone receptor (HR) positive and human epidermal growth factor receptor-2 (HER2) negative type comprising 65.9% of the cases, whereas HR negative and HER2 positive type was the rarest comprising 10.2% of the cases. The 5-year relative survival rate of breast cancer patients had increased by 14.0% from 79.2% in 1993-1995 to 93.2% in 2013-2017. It is essential to actively enter breast cancer data into the KBCS registry to improve our understanding.

Risk factor for contralateral occult carcinoma in patients with unilateral papillary thyroid carcinoma.

Purpose: The extent of surgery necessary in patients with unilateral papillary thyroid carcinoma (PTC) on preoperative radiologic imaging is still in doubt. In this study, we aimed to define risk factors that could be indicators for malignant nodules in the contralateral thyroid lobe. Methods: We included 438 patients who underwent total thyroidectomy between January 2011 and December 2014 at our institution. In this study, patients were divided into two groups according to the presence of contralateral occult carcinoma identified by postoperative pathological examination. We analyzed the clinicopathologic factors including characteristics of coexistent nodules in the contralateral lobe based on preoperative radiological imaging. Results: A total of 96 patients (21.9%) had PTC in the contralateral lobe. There were no significant differences between patients with or without contralateral occult carcinoma with respect to gender, age, primary tumor size, central lymph node metastasis, extrathyroidal extension and stage. The presence of Hashimoto's thyroiditis was an independent predictive factor for contralateral occult carcinoma (P=0.01). Conclusion: A risk factor for contralateral occult carcinoma in unilateral PTC patients is Hashimoto's thyroiditis. Therefore, more caution is needed when determining optimal surgical methods for PTC patients with Hashimoto's thyroiditis.

Erratum: Basic Findings Regarding Breast Cancer in Korea in 2015: Data from a Breast Cancer Registry.

[This corrects the article on p. 1 in vol. 21, PMID: 29628978.].

Basic Findings Regarding Breast Cancer in Korea in 2015: Data from a Breast Cancer Registry.

The Korean Breast Cancer Society (KBCS) has established a nationwide breast cancer database using an online registration program in 1996. The present study aimed to analyze the basic findings and trends of breast cancer in Korea in 2015 using the data provided by the Korea Central Cancer Registry and the KBCS. In 2015, a total of 22,550 patients were newly diagnosed with breast cancer, of which 3,331 were carcinoma in situ cases and 19,219 were invasive cancer cases. The incidence rate of breast cancer in Korea has steadily increased since the nationwide database was established, and the crude rate and age-standardized rate including that of carcinoma in situ, were 88.1 and 66.0 cases per 100,000 women, respectively. In terms of age, the incidence of breast cancer was the highest in the 40-49-year-old age group (7,889 patients, 35.0%). With regard to surgical procedure, breast-conserving surgery was frequently performed (62.3%). However, the rate of mastectomy has been gradually increasing since 2012, that is, from 32.3% in 2014 to 36.1% in 2015. The rate of early breast cancer has continued to increase, and that of stages III and IV breast cancer was only 9.1% at the time of diagnosis. However, the 5-year survival rate of patients with carcinoma in situ from 2011 to 2015 was 92.3%, which was 14.4% higher than that from 1993 to 1995 (77.9%). Analysis of data from the nationwide registry of breast cancer will not only help to understand the characteristics of breast cancer in individuals in Korea, but will also significantly contribute to the treatment and research of breast cancer. Therefore, a high quality database for breast cancer in Korea must be established by further initiating registration project and establishing an objective legal basis.

Prognostic significance of intraoperative macroscopic serosal invasion finding when it shows a discrepancy in pathologic result gastric cancer.

PURPOSE: Depth of wall invasion is an important prognostic factor in patients with gastric cancer, whereas the prognostic significance of intraoperative macroscopic serosal invasion (mSE) findings remain unclear when they show a discrepancy in pathologic findings. This study, therefore, assessed the prognostic significance of mSE. METHODS: Data from cohort of 2,835 patients with resectable gastric cancer who underwent surgery between 1990 and 2010 were retrospectively reviewed. RESULTS: The overall accuracy of mSE and pathologic results was 83.4%. The accuracy of mSE was 75.5% in pT2. On the other hand, the accuracy of pT3 dropped to 24.5%. According to mSE findings (+/-), the 5-year disease-specific survival (DSS) rate differed significantly in patients with pT2 (+; 74.2% vs. -; 92.0%), pT3 (+; 76.7% vs. -; 91.8%) and pT4a (+; 51.3% vs. -; 72.8%) (P < 0.001 each), but not in patients with T1 tumor. Multivariate analysis showed that mSE findings (hazard ratio [HR], 2.275; 95% confidence interval [CI], 1.148-4.509), tumor depth (HR, 6.894; 95% CI, 2.325-20.437), nodal status (HR, 5.206; 95% CI, 2.298-11.791), distant metastasis (HR, 2.881; 95% CI, 1.388-6.209), radical resection (HR, 2.002; 95% CI, 1.017-3.940), and lymphatic invasion (HR, 2.713; 95% CI, 1.424-5.167) were independent predictors of 5-year DSS rate. CONCLUSION: We observed considerable discrepancies between macroscopic and pathologic diagnosis of serosal invasion. However, macroscopic diagnosis of serosal invasion was independently prognostic of 5-year DSS. It suggests that because the pathologic results could not be perfect and the local inflammatory change with mSE(+) could affect survival, a combination of mSE(+/-) and pathologic depth may be predictive of prognosis in patients with gastric cancer.

Comparison of conventional thyroidectomy and endoscopic thyroidectomy via axillo-bilateral breast approach in papillary thyroid carcinoma patients.

BACKGROUND: Endoscopic thyroidectomy has been applied to solve the cosmetic problems that resulted from conventional thyroidectomy. The aim of this study was to evaluate and compare the surgical outcomes of conventional and endoscopic thyroidectomies via axillo-bilateral-breast approach (ABBA) in patients with papillary thyroid carcinoma (PTC). METHODS: Between May 2007 and February 2011, 1003 patients with PTC underwent thyroidectomies. The eight hundred and thirty patients underwent conventional thyroidectomy and 173 patients underwent endoscopic thyroidectomy via ABBA. Clinicopathologic characteristics, complications, and surgical completeness were analyzed. RESULTS: The mean age was 49.53 years who received a conventional thyroidectomy and 38.90 years in endoscopic thyroidectomy (P < 0.0001). The conventional thyroidectomy group underwent more extensive surgery than the endoscopic thyroidectomy group but the operation time was longer in the endoscopic thyroidectomy group (P < 0.0001). The mean hospitalization length was 6.98 days following open thyroidectomy and 6.40 days after endoscopic thyroidectomy (P = 0.003). The tumor size was larger in the conventional thyroidectomy group than the endoscopic thyroidectomy group and a lesser number of lymph nodes were retrieved in the endoscopic thyroidectomy group compared to the conventional thyroidectomy group (P < 0.0001). The postoperative complications and thyroglobulin levels in both groups were not significantly different. CONCLUSION: These results suggest that conventional and endoscopic thyroidectomy via ABBA has similar surgical outcomes in PTC patients. Therefore, endoscopic thyroidectomy via ABBA may be an appropriate surgical alternative to conventional thyroidectomy for treating PTC in selected patients.

Comparison of Learning Curves and Clinical Outcomes between Laparoscopy-assisted Distal Gastrectomy and Open Distal Gastrectomy.

PURPOSE: Most stomach surgeons have been educated sufficiently in conventional open distal gastrectomy (ODG) but insufficiently in laparoscopy-assisted distal gastrectomy (LADG). We compared learning curves and clinical outcomes between ODG and LADG by a single surgeon who had sufficient education of ODG and insufficient education of LADG. MATERIALS AND METHODS: ODG (90 patients, January through September, 2004) and LADG groups (90 patients, June 2006 to June 2007) were compared. The learning curve was assessed with the mean number of retrieved lymph nodes, operation time, and postoperative morbidity/mortality. RESULTS: Mean operation time was 168.3 minutes for ODG and 183.6 minutes for LADG. The mean number of retrieved lymph nodes was 37.9. Up to about the 20th to 25th cases, the slope decrease in the learning curve for LADG was more apparent than for ODG, although they both reached plateaus after the 50th cases. The mean number of retrieved lymph nodes reached the overall mean after the 30th and 40th cases for ODG and LADG, respectively. For ODG, complications were evenly distributed throughout the subgroups, whereas for LADG, complications occurred in 10 (33.3%) of the first 30 cases. CONCLUSIONS: Compared with conventional ODG, LADG is feasible, in particular for a surgeon who has had much experience with conventional ODG, although LADG required more operative time, slightly more time to get adequately retrieved lymph nodes and more complications. However, there were more minor problems in the first 30 LADG than ODG cases. The unfavorable results for LADG can be overcome easily through an adequate training program for LADG.