Primary apocrine sweat gland carcinomas of the axilla: a report of two cases and a review of the literature.

Primary apocrine sweat gland carcinoma (PASGC) is an extremely rare malignancy with a relatively favorable prognosis. PASGC is often suspected to be a benign disease during an initial clinical examination, which leads to inadequate initial treatment and extensive metastasis. Owing to the limited number of reports on PASGC, its diagnostic criteria and treatment guidelines have not yet been established. The only known curative therapy for localized PASGC is wide local excision. In the present report, we describe two cases of PASGC with locally aggressive disease that arose in the axilla and review the literature about its clinicopathological features, diagnosis, and treatment. Based on the findings of the current report, we suggest that a sentinel lymph node biopsy and adjuvant anti-estrogen therapy should be included in the management of PASGC.

Noninvasive Aortic Ultrafast Pulse Wave Velocity Associated With Framingham Risk Model: in vivo Feasibility Study.

BACKGROUND: Aortic pulse wave velocity (PWV) enables the direct assessment of aortic stiffness, which is an independent risk factor of cardiovascular (CV) events. The aim of this study is to evaluate the association between aortic PWV and CV risk model classified into three groups based on the Framingham risk score (FRS), i.e., low-risk (<10%), intermediate-risk (10~20%) and high-risk (>20%). METHODS: To noninvasively estimate local PWV in an abdominal aorta, a high-spatiotemporal resolution PWV measurement method (>1 kHz) based on wide field-of-view ultrafast curved array imaging (ufcPWV) is proposed. In the ufcPWV measurement, a new aortic wall motion tracking algorithm based on adaptive reference frame update is performed to compensate errors from temporally accumulated out-of-plane motion. In addition, an aortic pressure waveform is simultaneously measured by applanation tonometry, and a theoretical PWV based on the Bramwell-Hill model (bhPWV) is derived. A total of 69 subjects (aged 23-86 years) according to the CV risk model were enrolled and examined with abdominal ultrasound scan. RESULTS: The ufcPWV was significantly correlated with bhPWV (r = 0.847, p < 0.01), and it showed a statistically significant difference between low- and intermediate-risk groups (5.3 ± 1.1 vs. 8.3 ± 3.1 m/s, p < 0.01), and low- and high-risk groups (5.3 ± 1.1 vs. 10.8 ± 2.5 m/s, p < 0.01) while there is no significant difference between intermediate- and high-risk groups (8.3 ± 3.1 vs. 10.8 ± 2.5 m/s, p = 0.121). Moreover, it showed a significant difference between two evaluation groups [low- (<10%) vs. higher-risk group (≥10%)] (5.3 ± 1.1 vs. 9.4 ± 3.1 m/s, p < 0.01) when the intermediate- and high-risk groups were merged into a higher-risk group. CONCLUSION: This feasibility study based on CV risk model demonstrated that the aortic ufcPWV measurement has the potential to be a new approach to overcome the limitations of conventional systemic measurement methods in the assessment of aortic stiffness.

Optimization of protein trans-splicing in an inducible plasmid display system for high-throughput screening and selection of soluble proteins.

Directed evolution is widely used to optimize protein folding and solubility in cells. Although the screening and selection of desired mutants is an essential step in directed evolution, it generally requires laborious optimization and/or specialized equipment. With a view toward designing a more practical procedure, we previously developed an inducible plasmid display system, in which the intein (auto-processing) and Oct-1 DNA-binding (DBD) domains were used as the protein trans-splicing domain and DNA-binding module, respectively. Specifically, the N-terminal (CfaN) and C-terminal (CfaC) domains of intein were fused to the C-terminal end of the His-tag and the N-terminal end of Oct-1 DBD to generate His6-CfaN and CfaC-Oct-1, respectively. For such a system to be viable, the efficiency of protein trans-splicing without the protein of interest (POI) should be maximized, such that the probability of occurrence is solely dependent on the solubility of the POI. To this end, we initially prevented the degradation of l-arabinose (the inducer of the PBAD promoter) by employing an Escherichia coli host strain deficient in the metabolism of l-arabinose. Given that a low expression of His6-CfaN, compared with that of CfaC-Oct-1, was found to be conducive to the generation to a soluble product of the protein trans-splicing event, we designed the expression of His6-CfaN and CfaC-Oct-1 to be inducible from the PBAD and PT7 promoters, respectively. The optimized system thus obtained enabled in vitro selection of the plasmid-protein complex with high yield. We believe that the inducible plasmid display system developed in this study would be applicable to high-throughput screening and/or selection of protein variants with enhanced solubility.

Real-Time Ultrasound Detection of Breast Microcalcifications Using Multifocus Twinkling Artifact Imaging.

Detecting microcalcifications (MCs) in real time is important in the guidance of many breast biopsies. Due to its capability in visualizing biopsy needles without radiation hazards, ultrasound imaging is preferred over X-ray mammography, but it suffers from low sensitivity in detecting MCs. Here, we present a new nonionizing method based on real-time multifocus twinkling artifact (MF-TA) imaging for reliably detecting MCs. Our approach exploits time-varying TAs arising from acoustic random scattering on MCs with rough or irregular surfaces. To obtain the increased intensity of the TAs from MCs, in MF-TA, acoustic transmit parameters, such as the transmit frequency, the number of focuses and f-number, were optimized by investigating acoustical characteristics of MCs. A real-time MF-TA imaging sequence was developed and implemented on a programmable ultrasound research system, and it was controlled with a graphical user interface during real-time scanning. From an in-house 3D phantom and ex vivo breast specimen studies, the MF-TA method showed outstanding visibility and high-sensitivity detection for MCs regardless of their distribution or the background tissue. These results demonstrated that this nonionizing, noninvasive imaging technique has the potential to be one of effective image-guidance methods for breast biopsy procedures.

Feasibility study using multifocal Doppler twinkling artifacts to detect suspicious microcalcifications in ex vivo specimens of breast cancer on US.

Multifocal Doppler twinkling artifact (MDTA) imaging has shown high detection rates of microcalcifications in phantom studies. We aimed to evaluate its performance in detecting suspicious microcalcifications in comparison with mammography by using ex vivo breast cancer specimens. We prospectively included ten women with breast cancer that presented with calcifications on mammography. Both digital specimen mammography and MDTA imaging were performed for ex vivo breast cancer specimens on the day of surgery. Five breast radiologists marked cells that included suspicious microcalcifications (referred to as 'positive cell') on specimen mammographic images using a grid of 5-mm cells. Cells that were marked by at least three readers were considered as 'consensus-positive'. Matched color Doppler twinkling artifact (CDTA) signals were compared between reconstructed US-MDTA projection images and mammographic images. The median detection rate for each case was 74.7% for positive cells and 96.7% for consensus-positive cells. Of the 10 cases, 90% showed a detection rate of ≥ 80%, with 50% of cases showing a 100% detection rate for consensus-positive cells. The proposed MDTA imaging method showed high performance for detecting suspicious microcalcifications in ex vivo breast cancer specimens, and may be a feasible approach for detecting suspicious breast microcalcifications with US.

Simultaneous production of 2'-fucosyllactose and difucosyllactose by engineered Escherichia coli with high secretion efficiency.

BACKGROUND AND AIM: Difucosyllactose (Di-FL) has strong antimicrobial activity against various pathogens, including group B Streptococcus, identified as the leading cause of neonatal sepsis. In this study, we sought to develop Escherichia coli as a microbial cell factory for efficiently producing Di-FL as well as 2'-fucosyllactose (2'-FL), the most abundant fucosylated oligosaccharide in human milk, by utilizing the salvage guanosine 5'-diphosphate (GDP)-l-fucose biosynthetic pathway. MAIN METHODS AND MAJOR RESULTS: The biosynthetic pathway for producing fucosylated oligosaccharides via the salvage pathway requires two enzymes, l-fucokinase/GDP-l-fucose phosphorylase (FKP) from Bacteroides fragilis and α-1,2-fucosyltransferase (FucT2) from Helicobacter pylori. To decrease the intracellular accumulation of 2'-FL while increasing substrate accessibility to FKP and FucT2, we evaluated whether extracellular secretion of FKP and FucT2 would enhance the production of fucosylated oligosaccharides. Among various engineered strains constructed in this study, the ΔLFAR-YA/FF+P-PLA2 strain expressing phospholipase A2 (PLA2 ) from Streptomyces violaceoruber, whose native signal peptide was replaced with the PelB signal peptide (P-PLA2 ), could secrete both FKP and FucT2 into the culture medium. Notably, it was observed that FKP and FucT2 present in the extracellular fraction could catalyze the synthesis of Di-FL from lactose and fucose. As a result, a batch fermentation with the ΔLFAR-YA/FF+P-PLA2 strain resulted in the production of 1.22 ± 0.01 g L-1 Di-FL and 0.47 ± 0.01 g L-1 2'-FL, whereas the control strain could only produce 0.65 ± 0.01 g L-1 2'-FL. CONCLUSIONS AND IMPLICATIONS: This study highlights the benefits of extracellular secretion of enzymes to improve biotransformation efficiency, as the transport of substrates and/or products across the cell membrane is limited.

3D microcalcification detection using a color Doppler twinkling artifact with optimized transmit conditions: Preliminary results.

PURPOSE: Mammography is the only method that has been proven to detect breast microcalcifications (MCs), but the sensitivity of mammography varies according to breast density. This paper proposes an ultrasound (US) color Doppler twinkling artifact (CDTA) method with optimized transmit conditions to identify breast MCs without ionizing radiation. METHODS: The transmit conditions for US color Doppler imaging (CDI) were optimized to enhance the sensitivity of the twinkling artifact (TA) that arises from random scattering on rough surfaces of breast MCs. To validate the proposed breast MC detection method, a chicken breast phantom with MC particles (groups of particles <400  µ m and <240  µ m ) was fabricated and scanned by a digital mammography system and an US research platform by an L11-5v linear array probe with a three-dimensional (3D) motion tracking system. RESULTS: From the phantom experiment, the proposed 3D CDTA imaging method with optimized transmit conditions (i.e., a center frequency of 5.0 MHz, an f-number of 1.3, and a peak negative pressure of 1.83 MPa) successfully detected all 16 MC particles, comparable to detection with mammography. For a human breast surgical specimen in the ex vivo study, all 10 MC clusters, marked by a radiologist on the mammogram, were identified with the proposed 3D CDTA imaging method. CONCLUSIONS: In the phantom and ex vivo breast specimen studies, the proposed 3D CDTA imaging method successfully detected MCs, and the spatial localization was highly correlated with the mammogram results. These results indicate that the proposed 3D CDTA imaging method has great potential for the detection of MCs without ionizing radiation.

The clinical significance of PINX1 expression in papillary thyroid carcinoma.

PIN2/TERF1 interacting telomerase inhibitor 1 (PINX1) is a telomerase inhibitor located on human chromosome 8p23 and also acts as a tumor suppressor in several types of cancers, including breast, gastric, ovarian, and bladder cancer. However, the role of PINX1 expression in papillary thyroid carcinoma (PTC) has not been defined. Therefore, we investigated the role of PINX1 expression in PTC by analyzing the correlation between PINX1 expression and various clinicopathological factors. Immunohistochemistry for PINX1 was performed using a tissue microarray of samples taken from the 160 patients with PTC. We also assessed mRNA and protein expression for PINX1 via quantitative real-time polymerase chain reaction and immunohistochemical analysis. Positive staining for PINX1 was found in 16.3% of PTC cases. PINX1 expression was significantly associated with tumor size, lymph node metastasis, telomerase reverse transcriptase, promoter mutation and recurrence. PINX1 mRNA expression was more pronounced in the recurrent group than in the nonrecurrent group. In addition, results of the binary logistic regression model showed that PINX1 protein expression had a significant influence on recurrence. We concluded that PINX1 expression was associated with several clinicopathological factors and had a significant influence on recurrence in patients with PTC. Therefore, PINX1 expression could be a useful prognostic marker in PTC patients.

Importance of Individual Ghost Cells in Fine-Needle Aspiration Cytology Diagnosis of Pilomatricoma.

BACKGROUND: Although histological diagnosis of pilomatricoma is not difficult because of its unique histological features, cytological diagnosis through fine-needle aspiration cytology (FNAC) is often problematic due to misdiagnoses as malignancy. METHODS: We reviewed the cytological features of 14 cases of histologically-proven pilomatricoma from Korea Cancer Center Hospital, with a discussion on the diagnostic pitfalls of FNAC. RESULTS: Among 14 cases of pilomatricoma, 10 (71.4%) were correctly diagnosed through FNAC, and two (14.3%) were misdiagnosed as carcinoma. Cytologically, all cases had easily recognizable clusters of basaloid cells and foreign body-type multinucleated cells. Although ghost cells were also found in all cases, some were inconspicuous and hardly recognizable due to their small numbers. CONCLUSIONS: An accurate diagnosis of pilomatricoma in FNAC is feasible with consideration of clinical information and close examination of ghost cells.

The Significance of TROP2 Expression in Predicting BRAF Mutations in Papillary Thyroid Carcinoma.

BACKGROUND: Trophoblast antigen 2 (TROP2) is a human trophoblast cell-surface glycoprotein that is overexpressed in several types of epithelial cancers, and is suggested to be associated with an unfavorable prognosis. BRAF mutations are the most common genetic alteration in papillary thyroid carcinoma (PTC). We evaluated the correlation between TROP2 expression and BRAF mutation in PTC. METHODS: First, we carried out pyrosequencing for BRAF mutations and immunohistochemistry for TROP2 expression with a tissue microarray consisting of 52 PTC cases. Membranous staining in at least 5% of tumor cells was designated as positive staining and we analyzed the relationship between TROP2 expression and diverse clinicopathological factors, including BRAF mutation. Second, we tested TROP2 mRNA expression in three thyroid cancer cell lines with BRAF mutations (BCPAP, SNU790, and 8505C) and a normal thyroid cell line. Additionally, we checked TROP2 protein levels in a normal thyroid cell line after introduction of the BRAF V600E mutation. RESULTS: In this study, 21 of 26 cases with BRAF mutation showed TROP2 immunoreactivity, whereas all 26 cases without BRAF mutation showed no immunoreactivity for TROP2 with a statistically significant difference (p<.001). Upregulation of TROP2 mRNA was observed in all three thyroid cancer cell lines, but not in the normal thyroid cell line. Interestingly, however, the TROP2 expression was increased in the normal thyroid cell line after introduction of the BRAF V600E mutation. CONCLUSIONS: Based on these results, we concluded that TROP2 expression is significantly associated with BRAF mutation and that TROP2 immunohistochemistry could be used for predicting BRAF mutations or diagnosing papillary thyroid carcinoma.

Cytological Features That Differentiate Follicular Neoplasm from Mimicking Lesions.

BACKGROUND: It is difficult to correctly diagnose follicular neoplasms (FNs) on fine-needle aspiration cytology (FNAC) because it shares many cytological features with other mimicking lesions. The aim of this study was to identify the cytological features that differentiate FNs from mimicking lesions. METHODS: We included the cytological slides from 116 cases of thyroid FN diagnosed on FNAC, and included their subsequent histological diagnoses. We evaluated the cytological architectural pattern and nuclear features of the lesions according to their histological groups. RESULTS: The final histological diagnoses of the 116 cases varied, and included 51 FNs (44%), 47 papillary thyroid carcinomas (40%) including follicular variant, and seventeen cellular nodular hyperplasias (15%). Regardless of the final histological diagnosis, microfollicular pattern was observed in most cases. On the other hand, trabecular pattern was identified in 34% of FNs, but not in any other lesions. Additionally, elongated nuclei and ground glass chromatin were found in only some papillary thyroid carcinomas. CONCLUSIONS: This study shows that the trabecular pattern is a representative cytological feature of FNs that can be used to distinguish FNs from mimicking lesions. In addition, nuclear shape and chromatin pattern can be used to further confirm the diagnosis of FNs from mimicking lesions through FNAC.