• Title, Summary, Keyword: IHC

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Chromogenic In Situ Hybridisation Test for Breast Cancer Patients with Equivocal IHC Results - a Study from Iran

  • Mehrazma, Mitra;Kalantari, Elham;Rezvani, Hamid;Bahar, Babak;Basi, Ali;Razavi, Seyed Mohsen;Rakhshani, Nasser
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.17
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    • pp.7695-7700
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    • 2015
  • Background: HER2/neu overexpression on cell membranes of breast cancer cells is due to HER2/neu gene amplification and it is important to identify potential candidates for anti HER2 therapy with trastuzumab. IHC, FISH and CISH are standard FDA approved assays currently used to determine HER2 status in routine practice. The aim of this study was to determine HER2 gene amplification, using the CISH method in breast carcinoma samples which had IHC +2 reactions. Materials and Methods: This study was conducted from 2008-2010 using 334 consecutive breast carcinoma samples referred from local laboratories to Mehr Hospital. CISH assays were performed for all cases, and IHC tests were also done for determining efficacy and accuracy of local labs. HER2 status in local IHC tests was compared with central IHC and CISH results. Results: Of 334 breast cancer patients, 16 were negative for HER2 IHC (0, +1), 201 cases were equivocal (+2), and 31 positive (+3). Of 334 referral cases, 88 were CISH positive (26.3%) and 246 were CISH negative (73.7%). Of 201 IHC +2 cases, HER2 gene amplification was observed in 42 cases (kappa: 0.42). A 29.9% concordance was found between local IHC and central IHC. Sensitivity and specificity of local IHC were 90% and 53.8%, respectively. Conclusions: Low accuracy of IHC results in local labs was associated with the following factors: using former FDA-approved criteria for HER2 interpretation, utilizing non-validated kits, and lack of any quality assurance program. Therefore, following the new 2014 ASCO/CAP guideline and comprehensive quality assurance should be implemented to ensure accuracy of HER2 testing.

A Study on the Application of International Hull Clauses(2003) - A Comparative on the General Average and Salvage - (국제선박보험약관의 활용 방안에 관한 연구 - 공동해손 및 구조비용에 관한 비교 분석 -)

  • Yun, Seung-Kuk;Lee, Jae-Bok
    • The Korean Research Institute of International Commerce and Law
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    • v.54
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    • pp.213-233
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    • 2012
  • International Hull Clauses(IHC(2003)) which have replaced the old system, Institute Time Clauses, Hull(ITCH), used more than 100 years in the shipping industry that did not fit the reality of the market and customs was announced in 01/11/2003 and was intended to supplement the existing issues to reflect the terms that had been used. IHC(2003) was composed of systematical and logical phrases to minimize the conflict which happened between the insured and the insurer after the incident. But IHC(2003) is being ignored by both the insured and the insurer in the shipping industry due to the differences in both positions. In addition, the studies about IHC(2003) in local academics are very low and many companies in the shipping industry are using both systems, IHC(2003) and ITCH so the usage of IHC(2003) is not so activated. Thus, this study will examines the main features and the compositions of IHC(2003) and compare IHC(2003) with ITCH(1983) in some provisions in both systems and then derive some similarities from the both systems and finally would suggest the necessity and validity of active use of IHC(2003).

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Predictive Value of IHC4 Score for Pathological Response to Neoadjuvant Chemotherapy in Hormone Receptor-Positive Breast Cancer

  • Elsamany, Shereef;Elmorsy, Soha;Alzahrani, Abdullah;Rasmy, Ayman;Abozeed, Waleed N;Mohammed, Amrallah A;Sherisher, Mohamed A;Abbas, Mohammed M;Mashhour, Miral
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.17
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    • pp.7975-7979
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    • 2015
  • Purpose: This study aimed to explore the value of IHC4 in predicting pathological response after neoadjuvant chemotherapy in patients with hormonal receptor (HR)-positive breast cancer (BC). Materials and Methods: In this retrospective exploratory study, data for 68 HR-positive BC patients who received neoadjuvant chemotherapy were recorded. IHC4 scores were calculated based on estrogen receptors/progesterone receptors, Ki-67 and HER2 status. Logistic and ordinal regression analyses in addition to likelihood ratio test were used to explore associations of IHC4 scores and other clinico-pathological parameters with pathological complete response (pCR) and pathological stage. Results: Taking the 25th percentile as the cut-off, a lower IHC4 score was associated with an increased probability of pCR (low; 52.9% vs. High; 21.6%, OR=4.1, 95% CI=1.28-13.16, p=0.018) and a lower pathological stage (OR=3.9, 95% CI=1.34-11.33, p=0.012). When the IHC4 score was treated as a continuous variable, a lower score was again associated with an increased probability of pCR (OR=1.010, 95% CI=1.001-1.018, p=0.025) and lower pathological stage (OR=1.009, 95% CI=1.002-1.017, P=0.008). Lower clinical stage was associated with a better pCR rate that was of borderline significance (P=0.056). When clinical stage and IHC4 score were incorporated together in a logistic model, the likelihood ratio test gave a P-value of 0.004 after removal of the IHC4 score and 0.011 after removal of the stage, indicating a more significant predictive value of the IHC4 score for pCR. Conclusions: This study suggests that the IHC4 score can predict pathological response to neoadjuvant chemotherapy in HR-positive BC patients. This finding now needs to be validated in a larger cohort of patients.

Protease antigen recovery induces non-specific reaction in B-Cells (Protease antigen recovery의 B-Cell에 대한 비특이반응 유발)

  • Kim, Ok-Jin;Yi, Seong-Joon
    • Korean Journal of Veterinary Pathology
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    • v.7 no.1
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    • pp.11-15
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    • 2003
  • Antigen retrieval (AR) techniques were widely used to recover the antigenicity from the fixed tissues, which were guided by the philosophy of rendering immunohistochemistry (IHC) applicable to routine formalin-fixed, paraffin-embedded tissues for wide application of IHC in research and clinical filed for morphological observation like as anatomy, histology and pathology. Protease antigen recovery (PAR) is an AR technique, which is obtained the antigen retrieve by using enzyme digestion, and commonly used in IHC field. However, during the IHC for the detection of ovine herpesvirus 2 (OvHV-2) antigen, we noted lymphocyte-like cells-specific staining in the infiltrated cells into various organs like as liver and kidney, which was also shown in the IHC tissues with isotype control. However, those signals were not observed in the tissues conducted with in situ hybridization. Therefore, we analyzed the specificity of the IHC detection results. We found that PAR may induce false-positive result during IHC in lymphocyte-like cells, which were infiltrated mainly around vessels and in interstitial tissues. Through the Phenotyping, we realized that those false-positive cells were B-cell-related cells. These results suggest that PAR, a AR using protease, may induce non-specific false-positive reactions during IHC.

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Detection of HER2 Status in Breast Cancer: Comparison of Current Methods with MLPA and Real-time RT-PCR

  • Pazhoomand, Reza;Keyhan, Elahe;Banan, Mehdi;Najmabad, Hossein;Karimlou, Masoud;Khodadad, Faranak;Iraniparast, Alireza;Feiz, Farnaz;Majidzadeh, Keivan;Bahman, Ideh;Moghadam, Fatemeh Aghakhani;Sobhani, Atoosa Madadkar;Abedin, Seyedeh Sedigheh;Muhammadnejad, Ahad;Behjat, Farkhondeh
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7621-7628
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    • 2013
  • Human epidermal growth factor receptor (HER) status is an important prognostic factor in breast cancer. There is no globally accepted method for determining its status, and which method is most precise is still a matter of debate. We here analyzed HER2 mRNA expression by quantitative reverse transcription-PCR (qRT-PCR) and HER2 DNA amplification using multiplex ligation-dependent probe amplification (MLPA). In parallel, we performed a routine evaluation of HER2 protein by immunohistochemistry (IHC). To assess the accuracy of the RT-PCR and MLPA techniques, a combination of IHC and fluorescence in situ hybridization (FISH) was used, substituting FISH when the results of IHC were ambiguous (2+) and for those IHC results that disagreed with MLPA and qRT-PCR, this approach being termed IHC-FISH. The IHC results for four samples were not compatible with the MLPA and qRT-PCR results; the MLPA and qRT-PCR results for these samples were confirmed by FISH. The correlations between IHC-FISH and qRT-PCR or MLPA were 0.945 and 0.973, respectively. The ASCO/CAP guideline IHC/FISH correlation with MLPA was (0.827) and with RT-PCR was (0.854). The correlations between the IHC results (0, 1+ as negative, and 3+ as positive) and qRT-PCR and MLPA techniques were 0.743 and 0.831, respectively. Given the shortcomings of IHC analysis and greater correlations between MLPA, qRT-PCR, and FISH methods than IHC analysis alone with each of these three methods, we propose that MLPA and real-time PCR are good alternatives to IHC. However a suitable cut-off point for qRTPCR is a prerequisite for determining the exact status of HER2.

Improved Harmonic-CELP Speech Coder with Dual Bit-Rates(2.4/4.0 kbps) (이중 전송률(2.4/4.0 kbps)을 갖는 개선된 하모닉-CELP 음성부호화기)

  • 김경민;윤성완;최용수;박영철;윤대희;강태익
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.28 no.3C
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    • pp.239-247
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    • 2003
  • This paper presents a dual-rate (2.4/4.0 kbps) Improved Harmonic-CELP(IHC) speech coder based on the EHC(Efficient Harmonic-CELP) which was presented by the authors. The proposed IHC employs the harmonic coding for voiced and the CELP for unvoiced segments. In the IHC, an initial voiced/unvoiced estimate is obtained by the pitch gain and energy. Then, the final V/UV mode is decided by using the frame energy contour. A new harmonic estimation combining peak picking and delta adjustment provides a more reliable harmonic estimation than that in the EHC. In addition, a noise mixing scheme in conjunction with an improved band voicing measurement provides the naturalness of the synthesized speech. To demonstrate the performance of the proposed IHC coder, the coder has been implemented and compared with the 2.0/4.0 kbps HVXC(Harmonic excitation Vector Coding) standardized by MPEG-4. Results of subjective evaluation showed that the proposed IHC coder and produce better speech quality than the HVXC, with only 40% complexity of the HVXC.

Effects of Banggihwanggi-Tang on Obesity-related Enteroendocrine Cells and Neuropeptides in Mice (방기황기탕(防己黃芪湯)이 생쥐의 비만관련 장내분비세포와 신경펩타이드에 미치는 영향)

  • Kim, Tae-Heon;Kim, Ho-Il;Lee, Kwang-Gyu;Lee, Sang-Ryong;Lee, Chang-Hyun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.26 no.4
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    • pp.497-505
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    • 2012
  • To determine the effects of Banggihwanggi-tang(BGHGT) on obesity, the obesity-related factors[gastrin, calcitonin gene related peptide(CGRP), serotonin, ghrelin, obestatin, glucagon-like peptide-1(GLP-1), insulin, orexin, leptin] were investigated in the stomach, pancreas, brain of mice by immunohistochemical(IHC) methods for 4 weeks. The change of body weight was more reduced in BGHGT administered group than that of control group. The IHC density of the gastrin and CGRP positive cells on pylorus was higher in BGHGT administered group than that of control group. The number of ghrelin immunoreactive cells on stomach was lower in BGHGT administered group than that of control group. The IHC of GLP-1 positive cells did not observe in the stomach of BGHGT administered groups. The IHC density of GLP-1 in the pancreas was lower in BGHGT administered group than that of control group. The IHC density of insulin positive cells in the pancreas was lower in BGHGT administered group than that of control group. The IHC density of orexin positive neurons in the diencephalon was slightly higher in BGHGT administered group than that of control group. The IHC density of NPY and leptin positive neurons was slightly higher in BGHGT administered group than that of control group. The IHC density of serotonin positive neurons was higher in BGHGT administered group than that of control group. Therefore, we conclude that BGHGT activates appetite inhibitor through appetite related enteroendocrine cells and neuropeptides in stomach, pancreas and brain, and this activation may also be responsible for the inhibition of feeding behavior.

Negative HER2/neu Amplification Using Immunohistochemistry and Chromogenic in Situ Hybridization Techniques in Skin Melanoma Cases

  • Shayanfar, Nasrin;Bahari, Leila;Safaie-Naraghi, Zahra;Kamyab, Kambiz;Gheytanchi, Elmira;Rezaei, Nima
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.2
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    • pp.421-425
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    • 2015
  • Background: This study was performed to evaluate the amplification of HER-2/neu in patients with melanoma. Materials and Methods: Amplification of HER-2/neu was evaluated in a group of patients with melanoma, referred to two referral centers in Tehran, using immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) techniques. Results: Forty patients with mean age $57.9{\pm}19.5years$ were enrolled in this study. The most frequent type of melanoma was acral, while lower limbs were the most frequent sites. The amplification of HER2/neu was negative in 97.5% of patients with IHC and in 100% of patients with CISH technique. Only one case (2.5%) shows weak positive staining (+2) in IHC method. Fifty five percent of melanoma was ulcerative, and the most common stages of tumors were stages 4b and 3b. More than 47% of cases were in Clark level III, while the mean of Breslow thickness was $3.56{\pm}2.87mm$. The stage of the case that showed weakly positive staining (2+) in IHC was 4b. Conclusions: The amplification of HER2/neu biomarker was negative in patients with melanoma, using both CISH and IHC techniques.

Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma: is it different between Over and Under 50 Years of Age?

  • Monabati, Ahmad;Vahedi, Amir;Safaei, Akbar;Noori, Sadat;Mokhtari, Maral;Vahedi, Leila;Zamani, Mehdi
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.4
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    • pp.2285-2289
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    • 2016
  • Background: Epstein-Barr virus (EBV) positive diffuse large B-cell lymphoma (DLBCL) of the elderly is an entity introduced in the latest WHO classification of lymphoid tumors and defined in patients older than 50 years without prior lymphoma or immunodeficiency. However, recently it has also been seen in patients under 50. There is thus debate as to whether these are separate entities. Materials and Methods: In this retrospective study, we analyzed de novo DLBCL admitted to our institute over a period of two years. Clinical data included age, sex, nodal and extranodal presentation. The results of an immunohistochemistry (IHC) panel were also reviewed. IHC findings were mainly used to sub-classify DLBCL as germinal center vs. non germinal center types. IHC for identification of LMP-1 (latent membrane protein) and in situ hybridization for detection of EBV-encoded RNA (EBER) was performed. EBV prevalence, clinical data and IHC findings were compared between patients under and over 50 years of age. Results: Out of 95 DLBCL, 11.6% were EBV positive (7.5% and 14.5% in the young and old groups). We did not find any significant differences in IHC subclasses and clinical data between EBV positive DLBCL (EBV+DLBCL) of young and old groups. Conclusions: EBV+DLBCL are not exclusive to patients older than 50 years. With regard to clinical data as well as IHC subclasses, no differences were evident between EBV+DLBCL of young and old groups. Our suggestion is to eliminate any cut off age for EBV+DLBCL.

Retrospective Study of ALK Rearrangement and Clinicopathological Implications in Completely Resected Non-small Cell Lung Cancer Patients in Northern Thailand: Role of Screening with D5F3 Antibodies

  • Tantraworasin, Apichat;Lertprasertsuke, Nirush;Kongkarnka, Sarawut;Euathrongchit, Juntima;Wannasopha, Yutthaphan;Saeteng, Somcharoen
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.7
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    • pp.3057-3063
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    • 2014
  • Background: Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC) has been intensively studied. The gold standard for ALK detection is FISH, but this is not routinely conducted in clinical practice, so that the IHC method has a role. The aim of this study was to identify the incidence of ALK rearrangement and risk or prognostic factors for ALK positivity using both of IHC and FISH methods. Materials and Methods: From January 2008 to December 2012, 267 completely resected NSCLC patients in Chiang Mai University Hospital were enrolled in this study. Clinical and pathological variables and outcomes of treatment were retrospectively reviewed. IHC and FISH were used to evaluate ALK rearrangement. Sensitivity and specificity of IHC were analyzed. Multivariable analysis was used to identify clinico-pathological correlations with positive results of IHC and clinical outcomes. Results: Twenty-two (8.2%) of 267 specimens were IHC-positive for ALK with intense cytoplasmic staining, whereas only 10 (3.8%) were FISH-positive. Sensitivity, specificity and the positive likelihood ratio with IHC were 80.0%, 94.9%, and 15.8 respectively. Age less than 55 years (RR 4.4, 95%CI 1.78-10.73, p value=0.001) and presence of visceral pleural invasion (VPI) (RR 2.9, 95%CI 1.21-6.78, p value =0.017) were identified as risk factors for ALK rearrangement with FISH. There were no statistically significant differences in other clinical and pathological variables. ALK rearrangement was not a prognostic factor for tumor recurrence or overall survival. Conclusions: The incidences of ALK positivity in completely resected NSCLCs in northern Thailand were 8.2% by IHC and 3.8% by FISH. IHC with mouse monoclonal, Ventana D5F3 antibody can be used as a screening tool before FISH method because of high specificity and high positive likelihood ratio. Age less than 55 years and VPI are risk factors for ALK positivity.