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Background@#The need for regulatory science development to evaluate advanced regulatory products is gradually increasing without hindering the technological development. Creating a research environment and fostering experts through the establishment of regulatory agency-led policies are essential for the development of regulatory science. Method: This is a comparative study of the United States, Japan, Singapore, and Korea. The literature and websites of each regulatory agency were reviewed, and the focus was on advantages and comparing advantages based on definition, development trends, and expert training projects. @*Results@#The United States is striving to develop regulatory science in response to changes in the new pharmaceutical industry through the regulatory science report, and to foster expert both inside and outside the Food and Drug Administration (FDA). Japan is promoting regulatory science centered on regulatory science centers, and is focusing on researching work-related regulatory science within the Pharmaceuticals and Medical Devices Agency (PMDA) and improving employees’ ability to make regulatory decisions. Singapore was aiming to improve Southeast Asia’s regulatory capabilities under the leadership of Centre of Regulatory Excellence (CoRE) within Duke-NUS University. In 2021, Korea is in its early stages, starting to run a university's degree program related to regulatory science this year. @*Conclusion@#Regulatory science should be developed with the aim of improving the regulatory ability of the Ministry of Food and Drug Safety with Korea’s independent concept of regulatory science.
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Background@#Pokemon is an oncogenic transcription regulator that plays a critical role in cellular differentiation. Although it has been found to be overexpressed in several types of cancer involving different organs, its role in thyroid gland has yet to be reported. The objective of this study was to evaluate the expression of Pokemon in papillary thyroid carcinoma (PTC) based on clinicopathological parameters. @*Methods@#Tissue microarray samples derived from patients with PTC or benign thyroid disease were used to evaluate Pokemon expression based on immunohistochemical analysis. Correlations of its expression with various clinicopathological parameters were then analyzed. @*Results@#Pokemon expression was observed in 22.0% of thyroid follicular cells from the normal group, 44.0% from the group with benign thyroid diseases, and 92.1% from the group with PTC (p < .001). The intensity of Pokemon expression was markedly higher in the PTC group. Pokemon expression level and PTC tumor size showed an inverse correlation. T1a tumors showed strong expression levels of Pokemon. However, larger tumors showed weak expression (p = .006). @*Conclusions@#Pokemon expression is associated with tumorigenesis of PTC, with expression showing an inverse correlation with PTC tumor size. This might be related to the negative regulation of aerobic glycolysis by Pokemon.
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Background@#Pokemon is an oncogenic transcription regulator that plays a critical role in cellular differentiation. Although it has been found to be overexpressed in several types of cancer involving different organs, its role in thyroid gland has yet to be reported. The objective of this study was to evaluate the expression of Pokemon in papillary thyroid carcinoma (PTC) based on clinicopathological parameters. @*Methods@#Tissue microarray samples derived from patients with PTC or benign thyroid disease were used to evaluate Pokemon expression based on immunohistochemical analysis. Correlations of its expression with various clinicopathological parameters were then analyzed. @*Results@#Pokemon expression was observed in 22.0% of thyroid follicular cells from the normal group, 44.0% from the group with benign thyroid diseases, and 92.1% from the group with PTC (p < .001). The intensity of Pokemon expression was markedly higher in the PTC group. Pokemon expression level and PTC tumor size showed an inverse correlation. T1a tumors showed strong expression levels of Pokemon. However, larger tumors showed weak expression (p = .006). @*Conclusions@#Pokemon expression is associated with tumorigenesis of PTC, with expression showing an inverse correlation with PTC tumor size. This might be related to the negative regulation of aerobic glycolysis by Pokemon.
ABSTRACT
The first edition of the ‘Standardized Pathology Report for Colorectal Cancer,’ which was developed by the Gastrointestinal Pathology Study Group (GIP) of the Korean Society of Pathologists, was published 13 years ago. Meanwhile, there have been many changes in the pathologic diagnosis of colorectal cancer (CRC), pathologic findings included in the pathology report, and immunohistochemical and molecular pathology required for the diagnosis and treatment of colorectal cancer. In order to reflect these changes, we (GIP) decided to make the second edition of the report. The purpose of this standardized pathology report is to provide a practical protocol for Korean pathologists, which could help diagnose and treat CRC patients. This report consists of “standard data elements” and “conditional data elements.” Basic pathologic findings and parts necessary for prognostication of CRC patients are classified as “standard data elements,” while other prognostic factors and factors related to adjuvant therapy are classified as “conditional data elements” so that each institution could select the contents according to the characteristics of the institution. The Korean version is also provided separately so that Korean pathologists can easily understand and use this report. We hope that this report will be helpful in the daily practice of CRC diagnosis.
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PURPOSE: BioPATH is a non-interventional study evaluating the relationship of molecular biomarkers (PTEN deletion/downregulation, PIK3CA mutation, truncated HER2 receptor [p95HER2], and tumor HER2 mRNA levels) to treatment responses in Asian patients with HER2+ advanced breast cancer treated with lapatinib and other HER2-targeted agents. MATERIALS AND METHODS: Female Asian HER2+ breast cancer patients (n=154) who were candidates for lapatinib-based treatment following metastasis and having an available primary tumor biopsy specimen were included. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, overall survival on lapatinib, correlation between biomarker status and PFS for any previous trastuzumab-based treatment, and conversion/conservation rates of the biomarker status between tissue samples collected at primary diagnosis and at recurrence/metastasis. Potential relationships between tumor mRNA levels of HER2 and response to lapatinib-based therapy were also explored. RESULTS: p95HER2, PTEN deletion/downregulation, and PIK3CA mutation did not demonstrate any significant co-occurrence pattern and were not predictive of clinical outcomes on either lapatinib-based treatment or any previous trastuzumab-based therapy in the metastatic setting. Proportions of tumors positive for p95HER2 expression, PIK3CA mutation, and PTEN deletion/down-regulation at primary diagnosis were 32%, 31.2%, and 56.2%, respectively. Despite limited availability of paired samples, biomarker status patterns were conserved in most samples. HER2 mRNA levels were not predictive of PFS on lapatinib. CONCLUSION: The prevalence of p95HER2 expression, PIK3CA mutation, and PTEN deletion/downregulation at primary diagnosis were similar to previous reports. Importantly, no difference was observed in clinical outcome based on the status of these biomarkers, consistent with reports from other studies.
Subject(s)
Female , Humans , Asian People , Biomarkers , Biopsy , Breast Neoplasms , Breast , Diagnosis , Disease-Free Survival , Neoplasm Metastasis , Prevalence , RNA, Messenger , TrastuzumabABSTRACT
BACKGROUND: Counting mitoses is subjective and time-consuming. The adjunctive diagnostic utility of a recently reported mitotic marker, phosphohistone H3 (PHH3), was investigated in gastrointestinal stromal tumors (GISTs). METHODS: We reviewed 77 GISTs for several proliferative indices. These included the mitotic count per 50 high power fields (HPFs), the immunohistochemical Ki-67 labeling index and the immunohistochemical PHH3 mitotic index (MI). For comparison, Spearman's rank correlation and interclass correlation coefficient were used. RESULTS: Mitotic counts ranged from 0-138 (mean, 7.57+/-2.34) and the PHH3 MI ranged from 0-126 per 50 HPFs (mean, 9.61+/-2.27). We found a positive correlation between mitotic counts and PHH3 MI (r=0.810, p<.001). The inter-observer correlation coefficient for three participants was 0.975 for mitotic counts and 0.940 for the PHH3 MI. When using the PHH3 MI instead of mitotic counts in the Armed Forces Institute of Pathology (AFIP) stratification criteria, 10 cases were reclassified. In one patient with a mitotic count of 2 and a PHH3 MI of 6 per 50 HPFs, distant metastasis occurred. CONCLUSIONS: In GISTs, the PHH3 MI correlated adequately with mitotic counts and can be used as a useful adjunctive to count mitotic figures efficiently.
Subject(s)
Humans , Arm , Biomarkers , Gastrointestinal Stromal Tumors , Mitosis , Mitotic Index , Neoplasm Metastasis , PathologyABSTRACT
BACKGROUND: While MUC2 is expressed in intestinal metaplasia and malignant lesions, the clinicopathological significance of MUC2 expression is not fully elucidated in gastric carcinoma (GC). METHODS: The present study investigated the correlation between MUC2 expression and clinicopathological parameters in 167 human GCs. In addition, to confirm the clinicopathological significance of MUC2 expression, we performed a systematic review and meta-analysis in 1,832 GCs. RESULTS: MUC2 expression was found in 58 of 167 GCs (34.7%). MUC2-expressing GC showed lower primary tumor (T), regional lymph node (N), and tumor node metastasis (TNM) stages compared with GCs without MUC2 expression (p=.001, p=.001, and p=.011, respectively). However, MUC2 expression was not correlated with Lauren's classification and tumor differentiation. In meta-analysis, MUC2 expression was significantly correlated with differentiation and lower tumor stage (odds ratio [OR], 1.303; 95% confidence interval [CI], 1.020 to 1.664; p = .034 and OR, 1.352; 95% CI, 1.055 to 1.734; p = .017, respectively) but not with Lauren's classification, pN stage, or pTNM stage. CONCLUSIONS: MUC2 expression was correlated with a lower tumor depth and lower lymph node metastasis in our study; the meta-analysis showed a correlation of MUC2 expression with tumor differentiation and lower tumor depth.
Subject(s)
Humans , Classification , Lymph Nodes , Metaplasia , Neoplasm MetastasisABSTRACT
Plexiform angiomyxoid myofibroblastic tumor (PAMT) of the stomach is a recently recognized entity. Because of its rarity, only 22 cases have been reported in the English-language literature and most of these are single case reports. We report two cases of gastric PAMT. The tumor cells were bland and plexiform arranged in a myxoid stroma, which was positive for alcian blue. Immunohistochemically, the tumor cells were positive for smooth muscle actin, but negative for c-kit, CD34, desmin, S-100 protein, epithelial membrane antigen, neurofilament, and protein kinase C-theta. Mutation analyses for exon 9, 11, 13, and 17 of KIT genes and 12, 14, and 18 of the platelet-derived growth factor receptor alpha (PDGFRA) genes were performed and the tumors were wild-type for mutation.
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Plexiform angiomyxoid myofibroblastic tumor (PAMT) of the stomach is a recently recognized entity. Because of its rarity, only 22 cases have been reported in the English-language literature and most of these are single case reports. We report two cases of gastric PAMT. The tumor cells were bland and plexiform arranged in a myxoid stroma, which was positive for alcian blue. Immunohistochemically, the tumor cells were positive for smooth muscle actin, but negative for c-kit, CD34, desmin, S-100 protein, epithelial membrane antigen, neurofilament, and protein kinase C-theta. Mutation analyses for exon 9, 11, 13, and 17 of KIT genes and 12, 14, and 18 of the platelet-derived growth factor receptor alpha (PDGFRA) genes were performed and the tumors were wild-type for mutation.
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OBJECTIVE: Lynch syndrome is a hereditary cancer syndrome that increases the risks of colorectal and gynecologic malignancies such as endometrial and ovarian cancer. Studies have shown that mutations in mismatch repair genes (MSH2, MSH6, and MLH1) are associated with Lynch syndrome. The aim of our study was to estimate the value of MSH2, MSH6, and MLH1 immunohistochemistry based on family history in a Korean sample. METHODS: Thirty six women with synchronous gynecologic tumors of endometrial and ovarian cancer were identified among patients being treated at our institution. Among them, 32 patients had tumor blocks (total 62 slides) available for analysis. According to a diagnostic algorithm, we performed immunohistochemistry analyses. Staining was scored based on intensity and proportion (negative or 0: intensity undetectable or minimal, proportion <5%; weak or 1+: intensity mild, proportion 5-30%; strong or 2+: intensity moderate to marked, proportion 30-99%). RESULTS: Among 32 eligible patients, 9 (28%) had a family history of cancer. Six patients (19%) were negative for MLH1; among them, four (4/6) were negative at both sites. Nine patients (28%) were negative for MSH2 or MSH6 at both sites or negative for both MSH2 and MSH6. Among these three patients showed negative staining for both sites. The three patients showing negative staining for MLH1, MSH2, and MSH6 at both sites with family history were considered to be the screening positive groups of Lynch syndrome. CONCLUSION: In this study, the frequency of Lynch syndrome associated immunohistochemical staining (MLH1, MSH2, and MSH6) group was estimated as 9% (3/32) among Korean women with synchronous gynecologic tumors.
Subject(s)
Female , Humans , Colorectal Neoplasms, Hereditary Nonpolyposis , DNA Mismatch Repair , Immunohistochemistry , Mass Screening , Negative Staining , Neoplastic Syndromes, Hereditary , Ovarian NeoplasmsABSTRACT
Colonic gastrointestinal stromal tumors (GISTs) are rare and behave aggressively compared to GISTs in other parts of the gastrointestinal tract. Therefore, accurate diagnosis of GISTs and their distinction from other mesenchymal tumors is important for proper patient management and follow-up. Herein, we present an unusual case of a colonic GIST mimicking an inflammatory fibroid polyp with a novel 63 bp deletion mutation in exon 11 of the c-kit gene, which has not previously been reported. The tumor consisted of loosely arranged spindle cells and many inflammatory cells scattered throughout the tumor. Immunohistochemically, the tumor cells were focally and weakly positive for c-kit and diffusely positive for CD34, but were negative for PKC-theta, SMA, S-100 protein, ALK-1, and desmin. Our case re-emphasizes the broad morphologic spectrum of GISTs.
Subject(s)
Humans , Colon , Colonic Polyps , Desmin , Exons , Follow-Up Studies , Gastrointestinal Stromal Tumors , Gastrointestinal Tract , Leiomyoma , Polyps , S100 Proteins , Sequence DeletionABSTRACT
BACKGROUND: Liqui-PREP(TM) (LP) is a new liquid-based cytologic preparation that produces a thin layer of cells. METHODS: Thyroid aspirates were obtained from 189 patients and divided to prepare pairs of conventional preparation (CP) and LP slides. The CP slides were routinely diagnosed by attending staffs and classified into the six categories. LP slides were independently evaluated by three cytopathologists and classified in an identical manner. Agreements between CP and LP diagnoses were investigated and interobserver variability of thyroid aspiration cytology results obtained using the LP method was determined using kappa values. RESULTS: CP and LP slides from 155 patients (83%) were identically classified by all of three cytopathologists. Concurrences between CP and LP diagnoses for the three cytopathologists were 89% (kappa=0.78), 92% (kappa=0.87), and 85% (kappa=0.70), respectively. Interobserver agreement among the three cytopathologists for LP slides ranged from substantial to almost perfect (kappa=0.84, 0.74 and 0.84). However, a lack of interobserver agreement was found for LP slides of the undetermined category as determined by original CP-based diagnoses. Moreover, cytomorphological alterations in the benign category appeared more worrisome for LP slides. CONCLUSIONS: An awareness of the novel cytomorphologic changes induced by the LP method is needed to avoid misinterpretations.
Subject(s)
Humans , Biopsy, Fine-Needle , Observer Variation , Thyroid GlandABSTRACT
BACKGROUND: Embryonic lethal abnormal vision (ELAV)-like protein HuR is known to stabilize mRNA through binding AU-rich elements in the 3'-untranslated region. Recent studies show that HuR expression is associated with the expression of several genes including cyclooxygenase-2 (COX-2). HuR exists predominantly in the nucleus, but cytoplasmic translocation of HuR is thought to be more important for its activity. COX-2 is a well-known enzyme that promotes tumor growth. METHODS: To evaluate the correlation of HuR and COX-2 expression, we analyzed expression of HuR and COX-2 in 91 cases of breast cancer using immunohistochemistry. RESULTS: Nuclear and cytoplasmic expression of HuR was seen in 76 (83.5%) and 19 (20.9%) of 91 cases respectively. COX-2 immunoreactivity was seen in 54 (59.4%) cases. Cytoplasmic HuR expression showed significant correlation with COX-2 expression (p=0.001). Nuclear HuR showed no correlation with COX-2 expression or other clinicopathological parameters. COX-2 expression is significantly associated with tumor grade (p=0.028). COX-2 (p=0.092) and cytoplasmic (p=0.569) and nuclear HuR (p=0.247) expression showed no correlation with survival. CONCLUSIONS: These results suggest that cytoplasmic HuR expression is associated with COX-2 expression in breast cancer and cytoplasmic location of HuR might contribute to the stabilization of COX-2 mRNA.
Subject(s)
Breast NeoplasmsABSTRACT
No abstract availble.
Subject(s)
Adult , Humans , Male , Arteries/abnormalities , Diagnosis, Differential , Endoscopy, Gastrointestinal , Gastrointestinal Hemorrhage/etiology , Intestinal Mucosa/blood supply , Jejunal Diseases/etiology , Jejunum/blood supplyABSTRACT
Pulmonary mixed squamous cell and glandular papillomas are extremely rare-only a few cases have been reported worldwide. We report a case of mixed squamous cell and glandular papilloma that presented as a solitary pulmonary nodule in a 53-year-old man. The tumor was located in the peripheral small bronchus of the posterobasal segment of the right lower lobe. Microscopically, the tumor was composed of papillary structures lined by squamous and glandular epithelium with mucous material. The fibrovascular cores showed lymphoplasmacytic infiltrates.
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A 46-year-old woman was found to have a huge liver mass that was detected by abdominal ultrasonography. Abdominal CT and MRI showed a 10 cm-sized, encapsulated mass occupying the anterior segment of the right hepatic lobe. Extended right hemihepatectomy was performed and pathological examination revealed fibroblast-like spindle cells within dense deposits of collagen. On immunohistochemical staining, these spindle tumor cells showed an intense CD34 immunoreactivity. The patient is alive without evidence of tumor recurrence 7 months after the resection. Solitary fibrous tumor is a very rare neoplasm found in the liver parenchyma, and it has been reported in less than 30 patients in the English literature. We present here the first such case in Korea.
Subject(s)
Female , Humans , Middle Aged , Antigens, CD34/analysis , Liver Neoplasms/diagnosis , Magnetic Resonance Imaging , Solitary Fibrous Tumors/diagnosis , Tomography, X-Ray Computed , Biomarkers, Tumor/analysisABSTRACT
BACKGROUND: The diagnosis of atypical mucosal lesions by performing hematoxylin-eosin staining is too subjective, and it is also subject to considerable inter-observer variation. There is a need for reliable immunohistochemical markers that can give reproducible results and that are not subject to individual interpretation. METHODS: We reviewed a total of 199 cases of gastric biopsy specimens, which were all diagnosed as atypical mucosal lesions, and 124 cases of the adenocarcinomas specimens had been classified from category 1 (C1) to C5 according to the Vienna classification. We also examined the immunohistochemical expressions of the glucose transporter GLUT1 and the p53 protein in the gastric biopsy specimens to determine if they were useful markers for differentiatial diagnosis under the Vienna classifications. RESULTS: None of the specimens in categories C1 to C3 showed GLUT1 expression, but 10.1% of the C4 specimens and 25.0% of the C5 specimens were GLUT1-positive (p<0.05). The expression of p53 was undetectable in the C1 specimens, but this was expressed in 2.9% of the C2 specimens, 15.6% of the C3 specimens, 37.8% of the C4 specimens, and 65.3% of the C5 specimens (p<0.05). CONCLUSIONS: The Vienna classification is very applicable to the gastric biopsy specimens of the atypical mucosal lesions, and the GLUT1 and p53 expressions are candidates as highly useful markers to differentiate the Vienna C4 lesions from the C3 and C5 lesions.
Subject(s)
Adenocarcinoma , Biopsy , Classification , Diagnosis , Glucose Transport Proteins, Facilitative , Glucose Transporter Type 1 , Observer Variation , Stomach , Tumor Suppressor Protein p53ABSTRACT
Jacobsen syndrome is a rare condition associated with the deletion of the long arm of chromosome 11. Though several authors reported prenatal sonographic findings of the Jacobsen syndrome, there are no common disease-specific features. The majority of affected cases were identified postnatally by chromosomal analysis of the dysmorphic or mentally retarded patients. We present a prenatal case of Jacobsen syndrome with a brief review of literature. A routine scanning in a 32-year-old primigravida at 17.3 weeks' gestation showed abnormal ultrasonographic findings consistent with increased nuchal thickening and subtle cardiac abnormalities (levorotated heart axis of greater than 60 degrees and thickened ventricular wall). The patient underwent amniocentesis, and the karyotype showed deletion of the long arm of chromosome 11, 46,XX, del (11) (q23.1q24). The fetal autopsy performed following medical termination confirmed the prenatal findings. The present case represents that the prenatal sonographic detection of the nuchal thickening and subtle cardiac abnormality should warrant a careful assessment of fetal anatomy and prompt cytogenetic analysis looking for chromosomal aberrations.