137,318 research outputs found
Comparing computer-generated and pathologist-generated tumour segmentations for immunohistochemical scoring of breast tissue microarrays
BACKGROUND: Tissue microarrays (TMAs) have become a valuable resource for biomarker expression in translational research. Immunohistochemical (IHC) assessment of TMAs is the principal method for analysing large numbers of patient samples, but manual IHC assessment of TMAs remains a challenging and laborious task. With advances in image analysis, computer-generated analyses of TMAs have the potential to lessen the burden of expert pathologist review. METHODS: In current commercial software computerised oestrogen receptor (ER) scoring relies on tumour localisation in the form of hand-drawn annotations. In this study, tumour localisation for ER scoring was evaluated comparing computer-generated segmentation masks with those of two specialist breast pathologists. Automatically and manually obtained segmentation masks were used to obtain IHC scores for thirty-two ER-stained invasive breast cancer TMA samples using FDA-approved IHC scoring software. RESULTS: Although pixel-level comparisons showed lower agreement between automated and manual segmentation masks (Îş=0.81) than between pathologists' masks (Îş=0.91), this had little impact on computed IHC scores (Allred; [Image: see text]=0.91, Quickscore; [Image: see text]=0.92). CONCLUSIONS: The proposed automated system provides consistent measurements thus ensuring standardisation, and shows promise for increasing IHC analysis of nuclear staining in TMAs from large clinical trials
Challenges of systematic reviewing integrative health care.
This article is based on an extensive review of integrative medicine (IM) and integrative health care (IHC). Since there is no general agreement of what constitutes IM/IHC, several major problems were identified that make the review of work in this field problematic. In applying the systematic review methodology, we found that many of those captured articles that used the term integrative medicine were in actuality referring to adjunctive, complementary, or supplemental medicine. The objective of this study was to apply a sensitivity analysis to demonstrate how the results of a systematic review of IM and IHC will differ according to what inclusion criteria is used based on the definition of IM/IHC. By analyzing 4 different scenarios, the authors show that, due to unclear usage of these terms, results vary dramatically, exposing an inconsistent literature base for this field
Systematic assessment of HER2/neu in gynecologic neoplasms, an institutional experience.
BackgroundHER2/neu overexpression and/or amplification has been widely studied in a number of solid tumors, primarily in the breast. In gynecologic neoplasms, determination of HER2/neu status has not been well studied as a predictive biomarker in anti-HER2/neu treatment.MethodsWe systematically evaluated the HER2/neu reactions by immunohistochemistry and fluorescent in situ hybridization in malignant gynecologic neoplasms as experienced in our institution.ResultsThe HER2/neu overexpression or amplification occurred in 8Â % of the cancers of the gynecological organs in our series. Majority of the HER2/neu overexpression and/or amplification occurred in clear cell (27Â %) and serous (11Â %) carcinomas. HER2/neu positivity was also seen in undifferentiated as well as in mixed clear cell and serous carcinomas. Discordant IHC and FISH results (positive by FISH but not IHC) was seen in 2 cases. Majority of the HER2/neu overexpression and/or amplification occurs in the endometrium rather than the ovary. Heterogeneity of the HER2/neu by IHC staining was inâ<â2Â % of the tumors in our series.ConclusionsWe recommend the HER2/neu studies on MĂźllerian carcinomas of clear cell, serous, and undifferentiated types, particularly when they arise in the endometrium. Since there are some discordant IHC/FISH results, we also propose performing the HER2/neu testing by FISH when the IHC score is less than 3â+â
Mechanisms of synaptic depression at the hair cell ribbon synapse that support auditory nerve function
Inner hair cells (IHCs) in the cochlea are the mammalian phono-receptors, transducing sound energy into graded changes in membrane potentials, the so called âreceptor potentials.â Ribbon synapses between IHCs and auditory nerve neurons are responsible for converting receptor potentials into spike rates. The characteristics of auditory nerve responses to sound have been described extensively. For instance, persistent acoustic stimulation produces sensory adaptation, which is revealed as a reduction in neuronal spike rate with time constants in the range of milliseconds to seconds. Since the amplitude of IHC receptor potentials is invariant during this period, the classic hypothesis pointed to vesicle depletion at the IHC as responsible for auditory adaptation. In this study, we observed that fast synaptic depression occurred in responses to stimuli of varying intensities. Nevertheless, release continued after this initial depression, via synaptic vesicles with slower exocytotic kinetics. Heterogeneity in kinetic elements, therefore, favored synaptic responses with an early peak and a sustained phase. The application of cyclothiazide (CTZ) revealed that desensitization of postsynaptic receptors contributed to synaptic depression, which was more pronounced during stronger stimulation. Thus, desensitization had a twofold effect: It abbreviated signaling between IHC and the auditory nerve and also balanced differences in decay kinetics between responses to different stimulation strengths. We therefore propose that both pre- and postsynaptic mechanisms at the IHC ribbon synapse contribute to synaptic depression at the IHC ribbon synapse and spike rate adaptation in the auditory nerve.Fil: Goutman, Juan Diego. Consejo Nacional de Investigaciones CientĂficas y TĂŠcnicas. Instituto de Investigaciones en IngenierĂa GenĂŠtica y BiologĂa Molecular "Dr. HĂŠctor N. Torres"; Argentin
AIP and MEN1 mutations and AIP immunohistochemistry in pituitary adenomas in a tertiary referral center.
Background: Pituitary adenomas have a high disease burden due to tumor growth/
invasion and disordered hormonal secretion. Germline mutations in genes such as MEN1
and AIP are associated with early onset of aggressive pituitary adenomas that can be
resistant to medical therapy.
Aims: We performed a retrospective screening study using published risk criteria to
assess the frequency of AIP and MEN1 mutations in pituitary adenoma patients in a
tertiary referral center.
Methods: Pituitary adenoma patients with pediatric/adolescent onset, macroadenomas
occurring â¤30 years of age, familial isolated pituitary adenoma (FIPA) kindreds and
acromegaly or prolactinoma cases that were uncontrolled by medical therapy were
studied genetically. We also assessed whether immunohistochemical staining for
AIP (AIP-IHC) in somatotropinomas was associated with somatostatin analogs (SSA)
response.
Results: Fifty-five patients met the study criteria and underwent genetic screening for
AIP/MEN1 mutations. No mutations were identified and large deletions/duplications were
ruled out using MLPA. In a cohort of sporadic somatotropinomas, low AIP-IHC tumors
were significantly larger (P = 0.002) and were more frequently sparsely granulated
(P = 0.046) than high AIP-IHC tumors. No significant relationship between AIP-IHC and
SSA responses was seen.
Conclusions: Germline mutations in AIP/MEN1 in pituitary adenoma patients are rare and
the use of general risk criteria did not identify cases in a large tertiary-referral setting.
In acromegaly, low AIP-IHC was related to larger tumor size and more frequent sparsely
granulated subtype but no relationship with SSA responsiveness was seen. The genetics
of pituitary adenomas remains largely unexplained and AIP screening criteria could be
significantly refined to focus on large, aggressive tumors in young patients
GAN-based Virtual Re-Staining: A Promising Solution for Whole Slide Image Analysis
Histopathological cancer diagnosis is based on visual examination of stained
tissue slides. Hematoxylin and eosin (H\&E) is a standard stain routinely
employed worldwide. It is easy to acquire and cost effective, but cells and
tissue components show low-contrast with varying tones of dark blue and pink,
which makes difficult visual assessments, digital image analysis, and
quantifications. These limitations can be overcome by IHC staining of target
proteins of the tissue slide. IHC provides a selective, high-contrast imaging
of cells and tissue components, but their use is largely limited by a
significantly more complex laboratory processing and high cost. We proposed a
conditional CycleGAN (cCGAN) network to transform the H\&E stained images into
IHC stained images, facilitating virtual IHC staining on the same slide. This
data-driven method requires only a limited amount of labelled data but will
generate pixel level segmentation results. The proposed cCGAN model improves
the original network \cite{zhu_unpaired_2017} by adding category conditions and
introducing two structural loss functions, which realize a multi-subdomain
translation and improve the translation accuracy as well. % need to give
reasons here. Experiments demonstrate that the proposed model outperforms the
original method in unpaired image translation with multi-subdomains. We also
explore the potential of unpaired images to image translation method applied on
other histology images related tasks with different staining techniques
Variability in disease phenotypes within a single PRNP genotype suggests the existence of multiple natural sheep scarpie strains within Europe
Variability of pathological phenotypes within classical sheep scrapie cases has been reported for some time, but in many instances it has been attributed to differences in the PRNP genotype of the host. To address this issue we have examined by immunohistochemistry (IHC) and Western blotting (WB) for the disease-associated form of the prion protein (PrPd), the brains of 23 sheep from five European countries, all of which were of the same ARQ/ARQ genotype. As a result of IHC examinations, sheep were distributed into five groups with different phenotypes and the groups were the same regardless of the scoring method used, âlongâ or âshortâ PrPd profiling. The groups made did not respond to the geographical origin of the cases and did not correlate with the vacuolar lesion profiles, which showed a high individual variability. Discriminatory IHC and WB methods coincided to detect a âCH1641-likeâ case but otherwise correlated poorly in the classification of disease phenotypes. No other polymorphisms of the PRNP gene were found that could account for the pathological differences, except perhaps for a sheep from Spain with a mutation at codon 103 and a unique pathological phenotype. Preliminary evidence indicates that those different IHC phenotypes correlate with distinct biological properties on bioassay, suggesting that they are indicative of strain diversity. We therefore conclude that natural scrapie strains exist and that they can be revealed by detailed pathological examinations, which can be harmonized between laboratories to produce comparable results
Automated Segmentation of Cells with IHC Membrane Staining
This study presents a fully automated membrane segmentation technique for immunohistochemical tissue images with membrane staining, which is a critical task in computerized immunohistochemistry (IHC). Membrane segmentation is particularly tricky in immunohistochemical tissue images because the cellular membranes are visible only in the stained tracts of the cell, while the unstained tracts are not visible. Our automated method provides accurate segmentation of the cellular membranes in the stained tracts and reconstructs the approximate location of the unstained tracts using nuclear membranes as a spatial reference. Accurate cell-by-cell membrane segmentation allows per cell morphological analysis and quantification of the target membrane proteins that is fundamental in several medical applications such as cancer characterization and classification, personalized therapy design, and for any other applications requiring cell morphology characterization. Experimental results on real datasets from different anatomical locations demonstrate the wide applicability and high accuracy of our approach in the context of IHC analysi
Boolean analysis identifies CD38 as a biomarker of aggressive localized prostate cancer.
The introduction of serum Prostate Specific Antigen (PSA) testing nearly 30 years ago has been associated with a significant shift towards localized disease and decreased deaths due to prostate cancer. Recognition that PSA testing has caused over diagnosis and over treatment of prostate cancer has generated considerable controversy over its value, and has spurred efforts to identify prognostic biomarkers to distinguish patients who need treatment from those that can be observed. Recent studies show that cancer is heterogeneous and forms a hierarchy of tumor cell populations. We developed a method of identifying prostate cancer differentiation states related to androgen signaling using Boolean logic. Using gene expression data, we identified two markers, CD38 and ARG2, that group prostate cancer into three differentiation states. Cancers with CD38-, ARG2- expression patterns, corresponding to an undifferentiated state, had significantly lower 10-year recurrence-free survival compared to the most differentiated group (CD38+ARG2+). We carried out immunohistochemical (IHC) staining for these two markers in a single institution (Stanford; n = 234) and multi-institution (Canary; n = 1326) cohorts. IHC staining for CD38 and ARG2 in the Stanford cohort demonstrated that combined expression of CD38 and ARG2 was prognostic. In the Canary cohort, low CD38 protein expression by IHC was significantly associated with recurrence-free survival (RFS), seminal vesicle invasion (SVI), extra-capsular extension (ECE) in univariable analysis. In multivariable analysis, ARG2 and CD38 IHC staining results were not independently associated with RFS, overall survival, or disease-specific survival after adjusting for other factors including SVI, ECE, Gleason score, pre-operative PSA, and surgical margins
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