Clinicopathological and immunohistochemical characterization of papillary proliferation of the endometrium: A single institutional experience.

Papillary proliferation of the endometrium is an unusual lesion that is composed of papillae with fibrovascular stromal cores covered with benign-appearing glandular epithelium. We studied the clinicopathological and immunohistochemical features of four cases of endometrial papillary proliferations. All patients were postmenopausal. Two lesions were incidental findings in hysterectomy specimens, and two lesions were detected in endometrial curettage specimens. Based on the degree of architectural complexity and extent of proliferation, we classified papillary proliferations histopathologically into "simple" or "complex" growth patterns. Three cases were classified as simple papillary proliferation, and one case was classified as complex papillary proliferation. Simple papillary proliferations were characterized by slender papillae with delicate stromal cores. In contrast, complex papillary proliferations had intracystic papillary projections and cellular clusters with frequent branching and occasional cytological atypia. All cases showed coexistent metaplastic epithelial changes, including mucinous metaplasia, eosinophilic cell change, and ciliated cell metaplasia. One patient with simple papillary proliferations had coexistent well-differentiated endometrioid carcinoma. One patient had subsequent hyperplasia without atypia, and another patient had subsequent atypical hyperplasia/endometrioid intraepithelial neoplasia; both patients underwent total hysterectomy within four months. Our observations are consistent with previous data demonstrating that endometrial papillary proliferations coexist with or develop into atypical hyperplasia/endometrioid intraepithelial neoplasia or endometrioid carcinoma. It is very important for pathologists to discriminate papillary proliferations from neoplastic lesions (including atypical hyperplasia/endometrioid intraepithelial neoplasia and well-differentiated endometrioid carcinoma) and benign mimickers (including papillary syncytial metaplasia).ope

HoxB13 expression in ductal type adenocarcinoma of prostate: clinicopathologic characteristics and its utility as potential diagnostic marker

The histologic criteria and selective biomarkers of prostate ductal type adenocarcinoma (DAC) are relatively unknown compared to that known about acinar type adenocarcinoma (AAC). It is known that genetic alteration in Hox13 gene is associated with carcinogenesis of prostate cancer. In this study, we investigated clinicopathologic characteristics of HoxB13 expression in prostate cancer and compared clinicopathologic profiles of DAC and AAC of prostate. After slide review, some morphological variants of DAC, equivalent to Gleason pattern 3 and 5 of AAC were identified. High level of HoxB13 expression was identified in 46.5% (46 out of 99 cases) and 39.2% (31 out of 79 cases) of cases that belong to the training set and test set, respectively. In the training set, high level of HoxB13 expression was significantly correlated with DAC (P < 0.001), higher Gleason score (P < 0.001), advanced pathologic T stage (P = 0.010), and occurrence of biochemical recurrence (BCR; P < 0.001). The test set confirmed that high level of HoxB13 expression was associated with DAC (P < 0.001), higher Gleason score (P = 0.001), advanced pathologic T stage (P < 0.001), and occurrence of BCR (P < 0.001). Our findings suggest that HoxB13 may be a useful diagnostic marker for detection of DAC and a prognostic marker for prediction of BCR.ope

A Study on Measurement Evaluation of DOA Estimation Algorithm using Adaptive Array Antenna

Wireless communication technologies have greatly progressed in recent years and the markets, especially in the mobile communication, have been growing enormously. Moreover the next generation communication services will use higher frequency band, and require more channel capacity and wider bandwidth for a high-speed data communication. As a large increase in channel capacity and high transmission rates for wireless communications, the technologies for the power saving and efficient frequency usability are required. To meet the requirements of the next generation wireless communications, a system capable to automatically change the directionality of its radiation patterns in response to its signal environment must be indispensable. An adaptive array antenna system uses spatially separated antennas called array antenna and processes received signals with a digital signal processor after analog to digital conversion. The main concept of an adaptive antenna is the automatic or adaptive control of antenna's beam pattern by digital signal processing with a software algorithm. A digital device capable of high speed real-time processing, consuming low power and programmable is required for practical use of an adaptive antenna in wireless communications. In recent year using a FPGA(Field Programmable Gate Array) for the implementation of an adaptive antenna meets the requirements of high performance processing, programmability and low power consumption. This thesis describes a DOA(Direction Of Arrival) estimation algorithm using MUSIC(MUltiple SIgnal Classification) method with high resolution and evaluation of the DOA estimation measurement system using adaptive array antenna. The DOA estimation measurement system consists of linear array antenna, a DBF receiver, A/D control box and monitoring/control computer in the anechoic chamber. Transmitting part is composed broadband standard horn antenna and signal generator. The linear array antenna is fabricated and measured return loss is -16 dB and below at 2.09 GHz. The DBF(Digital Beam Forming) receiver is composed of 4-ch resistive FET mixer of low IF method. RF(Radio Frequency), LO(Local Oscillator) and an IF(Intermediate Frequency) signal considered in this thesis are 2.09 GHz, 2.08 GHz and 10 MHz, respectively. A/D control box has 12-bit resolution and sampling rates is up to 40 MHz. From results of the DOA estimation simulation using MATLAB, a zero IF is realized by DDC(Digital Down Conversion) and MUSIC algorithm with high resolution depends on the snapshot and antenna element number. In addition, A/D control box is implemented by MUSIC algorithm and IF signal generator. GUI(Graph User Interface) program for data control/monitoring in the computer is designed. From the results of the DOA estimation experiment, it confirms that a proposed DOA system is able to estimate the direction of incident wave.Abbreviations iii Abstract iv 제 1 장 서 론 1 1.1 연구배경 및 필요성 1 1.1.1 적응 배열 안테나 2 1.1.2 FPGA 4 1.1.3 SDR 8 1.2 연구목적 9 제 2 장 적응 배열 안테나 시스템 구성 11 2.1 수신기의 구조 11 2.1.1 기저대역 샘플링 11 2.1.2 IF 샘플링 13 2.2 A/D 컨트롤 박스 15 2.2.1 A/D 컨트롤 박스의 구성 15 2.2.2 FPGA의 회로구현 20 제 3 장 DOA 추정 알고리즘 21 3.1 서론 21 3.2 MUSIC 알고리즘 21 3.3 MATLAB을 이용한 시뮬레이션 24 3.3.1 DDC 24 3.3.2 NCO 24 3.3.3 LPF 25 3.4 A/D 컨트롤 박스의 성능수행 33 제 4장 DOA 측정시스템 구축 및 평가 34 4.1 배열 안테나의 제작 및 측정 34 4.2 DOA 추정 모델 40 4.3 측정시스템 성능평가 42 4.3.1 DOA 추정 결과 42 4.3.2 오차발생 원인 및 고찰 47 제 5 장 결 론 51 참고 문헌 5

Clinicopathological Characteristics of Squamous Cell Carcinoma and High-grade Squamous Intraepithelial Lesions Involving Endocervical Polyps

Background/aim: To investigate the clinicopathological characteristics of high-grade squamous intraepithelial lesions (HSILs) and squamous cell carcinomas (SCCs) involving endocervical polyps (ECPs). Patients and methods: We collected the endocervical polypectomy cases and performed pathological examination and cytohistological correlation. Results: During a period of 12 years, 21 (1.1%) HSILs and two (0.1%) SCCs involving ECPs were identified in 1,905 cases. Twelve (63.1%) of the 19 cases were cytohistologically concordant. In five HSILs and one SCC with polypectomy margin involvement, residual HSIL was identified in conization or hysterectomy specimens. Furthermore, in two HSIL patients and one SCC patient with negative polypectomy margins, residual HSILs were found in the conization specimens. Conclusion: The prevalence of HSIL and SCC involving ECP in our cohort was similar to the rates found in previous studies. The presence of residual HSIL in nonpolypoid cervical tissue regardless of the polypectomy margin involvement suggests that conization or hysterectomy is needed for diagnostic or treatment purposes.ope

Clinicopathological significance of intratumoral and peritumoral lymphocytes and lymphocyte score based on the histologic subtypes of cutaneous melanoma

The presence of tumor infiltrating lymphocytes is a favorable prognostic factor in cutaneous melanoma, but their clinicopathological significance in the intratumoral compartment compared to the peritumoral compartment is unclear. We investigated the clinicopathologic significance of tumor-infiltrating lymphocytes and lymphocyte score in intra- and peritumoral compartments in 177 Korean patients who had undergone surgical excision of cutaneous melanoma. No significant correlation was observed between various clinicopathologic factors and the presence of intratumoral lymphocytes. However, high peritumoral lymphocyte scores were associated with lower Clark levels (P = 0.001), shallower Breslow thicknesses (P = 0.006), and fewer mitotic counts (P = 0.01) than tumors with lower scores. There was a trend for longer disease-free survival in cases with peritumoral lymphocytes (P = 0.07) than those without peritumoral lymphocytes. In patients with acral lentiginous melanoma, a strong association between a high peritumoral lymphocyte score and shallow Clark level was apparent (P = 0.03), and the presence of peritumoral lymphocytes (P = 0.02) and a high intratumoral lymphocyte score (P = 0.04) was also associated with longer disease-free survival. Particularly, low intratumoral lymphocyte score remarkably affected tumor recurrence and distant metastasis in a multivariate analysis using Cox regression test (H.R. = 0.304, 95% C.I. = 0.078-1.185, P = 0.09). Thus, the presence of lymphocytes and high lymphocyte scores in the intratumoral and peritumoral compartments are valid prognostic factors in cutaneous melanoma.ope

Clinicopathologic Features and Molecular Characteristics of Glucose Metabolism Contributing to ¹⁸F-fluorodeoxyglucose Uptake in Gastrointestinal Stromal Tumors

Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET/CT) is useful in the preoperative diagnosis of gastrointestinal stromal tumors (GISTs); however, the molecular characteristics of glucose metabolism of GIST are unknown. We evaluated 18F-FDG uptake on preoperative PET/CT of 40 patients and analyzed the expression of glycolytic enzymes in resected GIST tissues by qRT-PCR, western blotting, and immunohistochemistry. Results of receiver operating characteristic curve analysis showed that the maximum standardized uptake value (SUVmax) cut-off value of 4.99 had a sensitivity of 89.5%, specificity was 76.2%, and accuracy of 82.5% for identifying tumors with a high risk of malignancy. We found that 18F-FDG uptake correlated positively with tumor size, risk grade, and expression levels of glucose transporter 1 (GLUT1), hexokinase 1 (HK1), and lactate dehydrogenase A (LDHA). Elevated HK and LDH activity was found in high-risk tumors. Among the isoforms of GLUT and HK, GLUT1 and HK1 expression increased with higher tumor risk grade. In addition, overexpression of glycolytic enzymes M2 isoform of pyruvate kinase (PKM2) and LDHA was observed in GISTs, especially in high-risk tumors. These results suggest that upregulation of GLUT1, HK1, PKM2, and LDHA may play an important role in GIST tumorigenesis and may be useful in the preoperative prediction of malignant potential.ope

Diagnostic algorithm for determining primary tumor sites using peritoneal fluid

This study was conducted to develop a novel algorithm for determining the origin of tumors by combining analysis of cluster patterns with immunocytochemistry (ICC) for markers in cells from fine-needle aspirates of ascites. We used LBC, based on SurePathTM (BD Diagnostics) technology, to screen 96 peritoneal fluid samples from patients with known malignancies and from 10 control patients with cirrhosis. Following dual ICC staining for cytokeratin 7 (CK7) and paired box gene 8 (PAX8), we developed an algorithm using immunoreactivity and three-dimensional (3D) cluster patterns to correlate staining and 3D cluster patterns with common primary origins that included stomach, ovarian, pancreatobiliary tract, colon, lung, and breast cancers. With the application of an automatic digitalized image analyzer, competence performance was analyzed using receiver operating characteristics (ROC) curve analysis. CK7 and PAX8 staining and 3D cluster patterns were used to differentiate primary origins. Samples from patients with stomach cancer were no 3D cluster /CK7+/PAX8- with area under the curve (AUC) of 0.8699 in ROC curve analysis. Samples from ovarian cancer patients were large 3D cluster/CK7+/PAX8+ with AUC of 0.9812. Samples from pancreatobiliary tract cancer patients were small 3D cluster/CK7+/PAX8- with AUC of 0.8772. The remaining cancer samples, including breast, lung and colon cancer samples, had similar patterns of large 3D clusters/CK7+/PAX8- with AUC of 0.882, especially for lung cancer. SurePathTM technology, using 3D cluster patterns and dual ICC for CK7 and PAX8 in peritoneal fluid samples, can provide important information for determining specific primary origins in cases of unknown primary carcinoma.ope

NADPH Oxidase 1 Activity and ROS Generation Are Regulated by Grb2/Cbl-Mediated Proteasomal Degradation of NoxO1 in Colon Cancer Cells

The generation of reactive oxygen species (ROS) is required for proper cell signaling, but must be tightly regulated to minimize deleterious oxidizing effects. Activation of the NADPH oxidases (Nox) triggers ROS production and, thus, regulatory mechanisms exist to properly control Nox activity. In this study, we report a novel mechanism in which Nox1 activity is regulated through the proteasomal degradation of Nox organizer 1 (NoxO1). We found that through the interaction between NoxO1 and growth receptor-bound protein 2 (Grb2), the Casitas B-lineage lymphoma (Cbl) E3 ligase was recruited, leading to decreased NoxO1 stability and a subsequent reduction in ROS generation upon epidermal growth factor (EGF) stimulation. Additionally, we show that EGF-mediated phosphorylation of NoxO1 induced its release from Grb2 and facilitated its association with Nox activator 1 (NoxA1) to stimulate ROS production. Consistently, overexpression of Grb2 resulted in decreased Nox1 activity, whereas knockdown of Grb2 led to increased Nox1 activity in response to EGF. CRISPR/Cas9-mediated NoxO1 knockout in human colon cancer cells abrogated anchorage-independent growth on soft agar and tumor-forming ability in athymic nude mice. Moreover, the expression and stability of NoxO1 were significantly increased in human colon cancer tissues compared with normal colon. Taken together, these results support a model whereby Nox1 activity and ROS generation are regulated by Grb2/Cbl-mediated proteolysis of NoxO1 in response to EGF, providing new insight into the processes by which excessive ROS production may promote oncogenic signaling to drive colorectal tumorigenesis.ope

External validation of chemotherapy response score system for histopathological assessment of tumor regression after neoadjuvant chemotherapy in tubo-ovarian high-grade serous carcinoma

OBJECTIVE: The chemotherapy response score (CRS) system based on histopathological examination has been recently proposed for tubo-ovarian high-grade serous carcinoma (HGSC) to assess response to neoadjuvant chemotherapy (NAC). This study was aimed at validating the CRS system in an external cohort of tubo-ovarian HGSC patients. METHODS: This study included 110 tubo-ovarian HGSC patients who underwent NAC followed by interval debulking surgery. The 3-tiered CRS of the omental and adnexal tissue sections was determined by 3 independent pathologists. Differences in patient outcomes according to CRS were analyzed. RESULTS: The CRS system was highly reproducible among the 3 pathologists. Fleiss' kappa value and Kendall's coefficient of concordance for the omental CRS were 0.656 and 0.669, respectively. The omental CRS significantly predicted progression-free survival (PFS). The median PFS of patients whose tumors exhibited the omental CRS 1-2 (15 months) was significantly shorter than that of patients with an omental CRS of 3 (19 months; p=0.016). In addition, after adjusting for age, stage, and debulking status, the omental CRS was an independent prognostic factor for PFS of tubo-ovarian HGSC patients who were treated with NAC (adjusted hazard ratio [HR]=1.74; 95% confidence interval [CI]=1.05-2.87). CONCLUSION: The CRS system for assessing NAC response was a reproducible prognostic tool in our cohort. The application of the CRS system after NAC can improve survival estimation in HGSC patients.ope

Stromal p16 expression is significantly increased in malignant ovarian neopla는

Alterations in p16 protein expression have been reported to be associated with tumor development and progression. However, p16 expression status in the peritumoral stroma has been rarely investigated. We investigated the stromal p16 expression in ovarian neoplasms using immunohistochemistry, and differences in the expression status depending on the degree of malignancy and histological type were analyzed. This study included 24, 21, and 46 cases of benign, borderline, and malignant ovarian lesions, respectively, of which 29, 25, and 32 cases were serous, mucinous, and endometriosis-associated lesions. Most benign lesions showed negative or weak expression, whereas borderline lesions showed focal, moderate expression. Malignant lesions showed markedly elevated stromal p16 expression compared with benign or borderline lesions. There were significant differences in stromal p16 expression between benign and borderline lesions (P < 0.001) and between borderline and malignant lesions (P < 0.001). These significances remained when analysis was performed based on lesion classification as serous, mucinous, and endometriosis-associated. In contrast, differences in stromal p16 expression among the histological types were not significant. Stromal p16 expression in ovarian neoplasms was absent or weak in benign and focal, moderate in borderline lesions, whereas malignant lesions exhibited diffuse, moderate-to-strong p16 immunoreactivity. Our observations suggest that stromal p16 expression is involved in the development of ovarian carcinoma. Further studies are necessary to confirm our preliminary results.ope