To ensure high-quality bioresources and standardize biobanks, there is an urgent need to develop and disseminate educational training programs in accordance with ISO 20387, which was developed in 2018. The standardization of biobank education programs is also required to train biobank experts. The subdivision of categories and levels of education is necessary for jobs such as operations manager (bank president), quality manager, practitioner, and administrator. Essential training includes programs tailored for beginner, intermediate, and advanced practitioners, along with customized training for operations managers. We reviewed and studied ways to develop an appropriate range of education and training opportunities for standard biobanking education and the training of experts based on KS J ISO 20387. We propose more systematic and professional biobanking training programs in accordance with ISO 20387, in addition to the certification programs of the National Biobank and the Korean Laboratory Accreditation System. We suggest various training programs appropriate to a student’s affiliation or work, such as university biobanking specialized education, short-term job training at unit biobanks, biobank research institute symposiums by the Korean Society of Pathologists, and education programs for biobankers and researchers. Through these various education programs, we expect that Korean biobanks will satisfy global standards, meet the needs of users and researchers, and contribute to the advancement of science.
Background Mutations in the KRAS gene have been identified in approximately 50% of colorectal cancers (CRCs). KRAS mutations are well established biomarkers in anti–epidermal growth factor receptor therapy. Therefore, assessment of KRAS mutations is needed in CRC patients to ensure appropriate treatment.
Methods We compared the analytical performance of the cobas test to Sanger sequencing in 264 CRC cases. In addition, discordant specimens were evaluated by 454 pyrosequencing.
Results KRAS mutations for codons 12/13 were detected in 43.2% of cases (114/264) by Sanger sequencing. Of 257 evaluable specimens for comparison, KRAS mutations were detected in 112 cases (43.6%) by Sanger sequencing and 118 cases (45.9%) by the cobas test. Concordance between the cobas test and Sanger sequencing for each lot was 93.8% positive percent agreement (PPA) and 91.0% negative percent agreement (NPA) for codons 12/13. Results from the cobas test and Sanger sequencing were discordant for 20 cases (7.8%). Twenty discrepant cases were subsequently subjected to 454 pyrosequencing. After comprehensive analysis of the results from combined Sanger sequencing–454 pyrosequencing and the cobas test, PPA was 97.5% and NPA was 100%.
Conclusions The cobas test is an accurate and sensitive test for detecting KRAS-activating mutations and has analytical power equivalent to Sanger sequencing. Prescreening using the cobas test with subsequent application of Sanger sequencing is the best strategy for routine detection of KRAS mutations in CRC.
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Background The pathologic distinction between high-grade prostate adenocarcinoma (PAC) involving the urinary bladder and high-grade urothelial carcinoma (UC) infiltrating the prostate can be difficult. However, making this distinction is clinically important because of the different treatment modalities for these two entities.
Methods A total of 249 patient cases (PAC, 111 cases; UC, 138 cases) collected between June 1995 and July 2009 at Seoul St. Mary’s Hospital were studied. An immunohistochemical evaluation of prostatic markers (prostate-specific antigen [PSA], prostate-specific membrane antigen [PSMA], prostate acid phosphatase [PAP], P501s, NKX3.1, and α-methylacyl coenzyme A racemase [AMACR]) and urothelial markers (CK34βE12, p63, thrombomodulin, S100P, and GATA binding protein 3 [GATA3]) was performed using tissue microarrays from each tumor.
Results The sensitivities of prostatic markers in PAC were 100% for PSA, 83.8% for PSMA, 91.9% for PAP, 93.7% for P501s, 88.3% for NKX 3.1, and 66.7% for AMACR. However, the urothelial markers CK34βE12, p63, thrombomodulin, S100P, and GATA3 were also positive in 1.8%, 0%, 0%, 3.6%, and 0% of PAC, respectively. The sensitivities of urothelial markers in UC were 75.4% for CK34βE12, 73.9% for p63, 45.7% for thrombomodulin, 22.5% for S100P, and 84.8% for GATA3. Conversely, the prostatic markers PSA, PSMA, PAP, P501s, NKX3.1, and AMACR were also positive in 9.4%, 0.7%, 18.8%, 0.7%, 0%, and 8.7% of UCs, respectively.
Conclusions Prostatic and urothelial markers, including PSA, NKX3.1, p63, thrombomodulin, and GATA3 are very useful for differentiating PAC from UC. The optimal combination of prostatic and urothelial markers could improve the ability to differentiate PAC from UC pathologically.
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Background: Inter-observer and intra-observer variation in histologic tumor grading are well documented. To determine whether histologic disorderliness in the arrangement of tumor cells may serve as an objective criterion for grading, we tested the hypothesis the degree of disorderliness is related to the degree of tumor differentiation on which tumor grading is primarily based. Methods: Borrowing from the statistical thermodynamic definition of entropy, we defined a novel mathematical formula to compute the relative degree of histologic disorderliness of tumor cells. We then analyzed a total of 51 photomicrographs of normal colorectal mucosa and colorectal adenocarcinoma with varying degrees of differentiation using our formula. Results: A one-way analysis of variance followed by post hoc pairwise comparisons using Bonferroni correction indicated that the mean disorderliness score was the lowest for the normal colorectal mucosa and increased with decreasing tumor differentiation. Conclusions: Disorderliness, a pathologic feature of malignant tumors that originate from highly organized structures is useful as an objective tumor grading proxy in the field of digital pathology.
BACKGROUND Mutations of c-MYC have been described in cervical cancer. However, association between c-MYC gene status and its prognostic significance have not been clarified. METHODS Tissue microarray sections from 144 patients with stage IB-IIB cervical cancer treated by radical hysterectomy were analyzed by fluorescence in situ hybridization using a region-specific probe for c-MYC and a centromere-specific probe for chromosome 8. RESULTS Seventy five percent (108/144) of c-MYC gain and 6.9% (10/144) of c-MYC gene amplification were observed.
c-MYC gene alteration was more frequently observed in squamous cell carcinoma than adenocarcinoma or adenosquamous carcinoma and were associated with low Ki67 labeling index (p=0.013). c-MYC amplification was not associated with clinicopathologic parameters except absence of bcl2 expression (p=0.048). Survival analysis revealed that patients with c-MYC amplification were significantly associated with higher risk of disease recurrence (p=0.007) and cancer related death (p=0.020). However, c-MYC gain was not associated with unfavorable outcome. Multivariate analysis proved c-MYC amplification as independent prognostic factors of shorter disease free survival and cancer-related death (p=0.028 and p=0.025, respectively). CONCLUSIONS c-MYC amplification, not gain, is an independent prognostic marker for shorter disease free and cancer specific survival in cervical cancer treated by radical hysterectomy.
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BACKGROUND The identification of monoclonality has been widely used for making diagnoses of lymphoproliferative lesions. Awareness of the sensitivity and detection limit of the technique used would be important for the data to be convincing. METHODS We investigated the minimum requirement of cells and sensitivity of gel electrophoresis (GE) and laser-induced fluorescence capillary electrophoresis (LFCE) for identifying IgH gene rearrangement using BIOMED-2 protocols. DNA extracted from Raji cells were diluted serially with peripheral blood mononuclear cells (PBMNCs) DNA. DNA from mixtures of diffuse large B-cell lymphoma (DLBCL) and reactive lymph nodes were also serially diluted. RESULTS For Raji cells, the detection limit was 62 and 16 cell-equivalents for GE and LFCE, respectively. In the condition with PBMNCs mixture, 2.5% and 1.25% of clonal cells was the minimum requirement for GE and LFCE, respectively. In 23% of DLBCL cells in tissue section, the detection limit was 120 and 12 cell-equivalents for GE and LFCE, respectively. In 3.2% of DLBCL cells, that was 1,200 and 120 cell-equivalents for GE and LFCE, respectively. CONCLUSIONS These results show that LFCE method is more sensitive than GE and the sensitivity of clonality detection can be influenced by the amount of admixed normal lymphoid cells.
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Apocrine carcinoma arising from the apocrine sweat glands is a rare cutaneous malignant tumor which occurs predominantly in the axilla of elderly individuals. The typical histologic features of apocrine carcinoma is within a well developed glandular lumina with abundant eosinophilic cytoplasm and evidence of decapitation secretion. In rare instances, predominant signet ring cell features in apocrine carcinoma has been reported. We experienced a case that occured in the right axilla of a 59-year-old. Histopathologic examination showed a solid tumor that extended from the upper dermis into the subcutis, with a delicate infiltrate of epithelial cells. The cells had granular amphophilic cytoplasm, predominantly showed distinct signet ring cell morphology, and were strongly positive for epithelial mucin. Both lysozyme and gross cystic disease fluid protein-15 were identified in the tumor cells. We diagnosed this to be a case of primary signet ring cell apocrine carcinoma of the axilla after several immunohistochemical and clinical evaluations.
BACKGROUND The grey zone of cervical cytology, and in particular atypical squamous cells, cannot exclude HSIL (ASC-H) causes diagnostic difficulties and increases medical expenses. We analyzed p16INK4a expression in ASC-H liquid-based cytology specimens (LBCS) to develop more effective methods for the management of ASC-H patients. METHODS We carried out p16INK4a immunostaining with 57 LBCS of ASC-H diagnostic categories, all of which were histologically cofirmed and 43 cases of which were compared with the results of a human papillomavirus (HPV) chip test. RESULTS p16INK4a immunostaining with ASC-H LBCS was positive in 20% (3/15) of cervicitis, 25.0% (3/12) of tissue-low-grade squamous intraepithelial lesion, 75.0% (18/24) of tissue-high grade squamous intraepithelial lesion (HSIL), and 100% (6/6) of invasive cancer cases. The positivity of p16INK4a in LBCS was correlated with higher grade of histologic diagnosis (r=0.578, p=0.000). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of p16INK4a immunostaining for the prediction of tissue-HSIL+ were 80.0%, 77.8%, 80.0%, and 77.8%, respectively. The sensitivity, specificity, PPV, and NPV of p16INK4a immunostaining plus HPV chip test for predicting tissue-HSIL+ were 71.2%, 86.4%, 84.2%, and 79.2%. CONCLUSIONS p16INK4a immunostaining as well as HPV chip testing with remaining LBCS with ASC-H are useful objective markers for the prediction of tissue-HSIL+.
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BACKGROUND BK virus nephropathy (BKVN) is an emerging problem as a consequence of the use of potent immunosuppressive agents. Because optimal detection methods for the diagnosis of BKVN are required clinically, we compared the results of renal allograft biopsy, urine cytology, and urine and blood viral loads. METHODS Four hundred sixty two case notes from 2004 to 2009 at Seoul St. Mary's Hospital were reviewed. During that period, 286 cases of urine cytology for decoy cells, 938 cases of urine BKV reverse transcription-polymerase chain reaction (RT-PCR), and 1,029 cases of blood BKV RT-PCR were performed. All diagnostic methods were performed in 85 cases. RESULTS A histological diagnosis of BKVN was made in 2.4% of cases (11/462). Urine cytology for decoy cells was positive in 26.2% (75/286). BKV RT-PCR revealed viruria in positivity of 22.1% (207/938) and viremia in 5.2% (54/1,029). In cases of BKVN, the sensitivities of urine and blood BKV RT-PCR were all 100% and the specificities were 69% and 94.5%, respectively. In cases with positive urine decoy cells, the sensitivities of urine and blood BKV RT-PCR were 50% and 27.7%, with specificities of 77.7% and 100%, respectively. CONCLUSIONS BKV screening by RT-PCR assays may be a clinically useful noninvasive test to identify renal recipients with concurrent BKVN.
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BACKGROUND To standardize renal biopsy reporting and diagnosis, The Renal Pathology Study Group of the Korean Society of Pathologists (RPSKSP) has developed a renal pathology reporting format for the native and allograft kidney. METHODS A consensus checklist of a provisional renal biopsy format was sent to all members of the RPSKSP. Feed back opinions regarding the practical application of the checklist to the diagnostic work were received. RESULTS Kidney biopsies require three essential examinations: by light microscopy, immunofluorescence (IF), and electron microscopy (EM). A final report of a renal biopsy should include information on specimen adequacy and a description of the morphologic change using a systematic semiquantitative method for each of the compartments, with optional separate IF and EM reports. CONCLUSIONS A standard renal biopsy report format is important in establishing clinicopathologic correlations, making reliable prognostic considerations, comparing the findings in sequential biopsies and evaluating the effects of therapy.
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Additional antihypertensive effect of magnesium supplementation with an angiotensin II receptor blocker in hypomagnesemic rats Kyubok Jin, Tae Hee Kim, Yeong Hoon Kim, Yang Wook Kim The Korean Journal of Internal Medicine.2013; 28(2): 197. CrossRef
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BACKGROUND Human papillomavirus (HPV) infection can be detected by in situ hybridization (ISH), in which a punctate signal pattern indicates integrated HPV DNA and a diffuse pattern denotes the presence of episomal viral DNA. This study was conducted to evaluate the usefulness of an HPV ISH assay for invasive cervical cancer. METHODS The HPV ISH assay for high-risk HPV and immunohistochemical staining for p16(INK4a), p53, bcl-2, and Ki-67 were performed in a tissue microarray of 279 cervical cancers. RESULTS High-risk HPV ISH was positive in 194 (69.5%) of the samples. Punctate, diffuse, and mixed signal patterns were observed in 157 (56.3%), one (0.4%), and 36 cases (12.9%), respectively. Positive results in high-risk HPV ISH were associated with p16 and bcl-2 expression (p = 0.01 and p < 0.01, respectively). According to a Cox regression analysis, HPV infection and its surrogate immunohistochemical markers such as p16, bcl-2, and Ki-67 were not independent prognostic factors, but stage and grade were independent prognostic factors. CONCLUSIONS Our results confirm that an HPV ISH assay is reasonably sensitive for HPV infection and that it might be useful to identify integrated HPV DNA in formalin-fixed and paraffin-embedded specimens. Further study encompassing HPV type, E2/E6 ratio, and therapeutic modality is necessary to understand the clinical meaning of HPV status in cervical cancer.
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BACKGROUND To determine the most effective method for detecting mycobacteria in formalin- fixed paraffin-embedded (FFPE) tissue, we compared the results of Ziehl-Neelsen stain (ZNS) and mycobacterial culture with those of polymerase chain reaction (PCR) and real-time quantitative PCR (RQ-PCR). METHODS We analyzed 54 cases diagnosed as chronic granulomatous inflammation. In all cases, ZNS and nested PCR using three different primers, IS6110, Mpb64 and IS6110/Rpobeta were done. RQ-PCR with the IS6110/Rpobeta primer was done in 51 cases. RESULTS Mycobacteria were identified by ZNS in 15/54 (27.8%) cases. RQ-PCR had the highest sensitivity (80.0%) compared to PCR with IS6110 (73.3%), Mpb64 (60.0%) and IS6110/Rpobeta (73.3%). Specificity was higher in all PCR experiments (79.5-82.1%) than in RQ-PCR (69.4%) experiments.
The false negative rate was lowest for RQ-PCR (20.0%) than for PCR with IS6110 (26.7%), Mpb64 (40.0%) and IS6110/Rpobeta (26.7%). The false positive rate was highest for RQ-PCR (30.6%) compared to PCR with IS6110 (20.5%), Mpb64 (17.9%) and IS6110/Rpobeta (20.5%). CONCLUSIONS RQ-PCR had the highest sensitivity, and the lowest false negative rate, but it also had a higher false positive rate than PCR for detection of mycobacteria in FFPE tissues.
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BACKGROUND Epidermal growth factor receptor (EGFR) is frequently expressed in the invasive front of colorectal cancer (CRC), but its clinicopathologic significance remains unclear. We investigated the clinical value of the EGFR expression at the invasive front of CRC. METHODS We performed an immunohistochemical analysis in order to examine the expression and distribution of EGFR in 214 cases of CRC. The EGFR status was considered positive when > or =1% of the tumor cells had membranous staining. RESULTS Overall, an EGFR expression was observed in 144 (67%) cases and it had no significant relationship with the clinicopathologic parameters. However, an EGFR expression at the invasive front was correlated with lymphatic invasion, lymph node metastasis and a high level of serum carcinoembryonic antigen (p = 0.028, p = 0.043, and p = 0.045, respectively). For the budding-positive CRCs liver metastases were found in the cases with an EGFR expression at the budding, but no liver metastasis occurred in the EGFR negative cases at the budding (p = 0.030). CONCLUSIONS An EGFR expression at the invasive front has clinicopathologic significances in patients with CRC. An EGFR expression at tumor cell budding is a pathologic marker that suggests the high potential for liver metastasis in CRC.
BACKGROUND C1q nephropathy (C1qN) is a controversial diagnostic entity defined by Jennette and Hipp in 1985. The prevalence is very low and a few large scale studies have been reported. Application of the criteria for clinical diagnostics of C1qN may cause confusion with other glomerulonephropathies, such as minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS). In order to clarify the confusion with glomerulonephropathies, we did this study to identify the clinicopathological characteristics and the exact disease entity of C1qN. METHODS A total of 5,258 kidney biopsies at Kangnam St Mary's Hospital were reviewed. Twenty three cases (0.44%) met the criteria of C1qN. Twenty eight cases showing dominant C1q deposits without electron dense depostis (EDD) grouped as C1q+EDD-, and previously diagnosed typical cases of MCD and FSGS were selected for this study. Four groups were compared to each other with regard to the clinical and pathological aspects of the disease. RESULTS: C1qN patients had an average age of 30.4 years. Eighteen were males and 5 were females. Eighty seven percent had proteinuria and 18% had hematuria. By electron microscopy analysis, 100% had mesangial EDD and 47.8% showed foot process effacement. C1qN had some significant differences compared with C1q+EDD-, MCD and FSGS. CONCLUSIONS: C1qN is clinically and morphologically different from MCD and FSGS. However, additional long term studies are needed to fully define C1qN from other glomerulonephritis with C1q deposits.
BACKGROUND IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide, and the clinical course of IgAN shows marked variability. Many efforts have made to histologically predict the clinical outcome. There are two methods to classify IgAN. One is mainly based on the glomerular changes, such as the WHO and the Lee and Haas classification systems. The other is a morphologic semi-quantitative scoring system, which counts the changes of the glomerular, tubulointerstitial and vascular structures, respectively. The purpose of this study is to determine whether the WHO classification properly reflects the various morphologic findings of IgAN. METHODS We analyzed 354 cases of IgAN by both the WHO classification system and the semiquantitative scoring system and evaluated the correlations of these two methods. RESULTS The severity of the glomerular lesions (glomerulosclerosis, capsular adhesion and mesangial matrix expansion) and the tubulointerstitial lesions (interstitial fibrosis, tubular atrophy and interstitial lymphocytic infiltration) are strongly correlated with the increase of the WHO classes of IgAN (Spearman's rho [R] > or =0.5, p<0.05). There is a weak correlation between crescent formation and the increase of the WHO classes (R=0.3, p<0.05). CONCLUSIONS This study shows that the WHO classification well reflects the severity of various morphologic findings and this suggests a complementary role for the semi-quantitative scoring system in classifying IgAN.
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The Oxford classification as a predictor of prognosis in patients with IgA nephropathy S. H. Kang, S. R. Choi, H. S. Park, J. Y. Lee, I. O. Sun, H. S. Hwang, B. H. Chung, C. W. Park, C. W. Yang, Y. S. Kim, Y. J. Choi, B. S. Choi Nephrology Dialysis Transplantation.2012; 27(1): 252. CrossRef