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- Karlsson, Mats G., 1960-, et al.
(författare)
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Quantitative computerized image analysis of immunostained lymphocytes : A methodological approach
- 1994
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Ingår i: Pathology, Research and Practice. - München, Germany : Elsevier. - 0344-0338 .- 1618-0631. ; 190:8, s. 799-807
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Tidskriftsartikel (refereegranskat)abstract
- A methodological approach by computerized image analysis to quantify immunostained objects in histological sections is described. We have investigated antibodies against CD4, CD8, CD20, CD23 and CD25 in frozen sections of human nasal mucosa; however, the methodology of standardization is of general validity. The study was designed particularly to investigate the following points: 1) light intensity, 2) the grey level for counter staining intensity, 3) the grey level threshold value for positive objects, 4) the minimal acceptable size of a positive object, 5) the influence of the brightness of the light on both the number and the area of objects. Furthermore, random sampling and determination of 6) the area per section, and 7) the number of histological sections to be measured per biopsy. Finally, a study of reproducibility of immunostaining intensity was performed. The influence of the different parameters mentioned above was studied and the values (eg. threshold value) for our particular setting of microscope, image analysis equipment, computer software etc, were defined. The method was then tested for intra- and interindividual variation which was found to be less than 5%. Correlation analysis of the reproducibility gave coefficients of correlation of 0.99, both concerning number of immunopositive objects and immunopositive area. We emphasize the importance of a highly standardized methodology if the numeric data obtained from computer assisted image analysis are to be more accurate than semiquantitative assessments by experienced observers. With a thorough standardization as described in this method it is possible to obtain numeric values, and data with low deviations, which are two obvious and important advantages.
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- Dimberg, Jan, et al.
(författare)
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Emerging role and clinical implication of mRNA scavenger decapping enzyme in colorectal cancer
- 2023
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Ingår i: Pathology, Research and Practice. - : Elsevier. - 0344-0338 .- 1618-0631. ; 253
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Turnover of RNA is a regulated process that in part controls gene expression. This process is partly controlled by the scavenger decapping enzyme (DcpS). This study aimed to investigate the expression of DcpS in colorectal cancer (CRC) tissue, to evaluate its prognostic significance in patients with CRC and to investigate potentially targeted genes by DcpS.METHODS: Immunohistochemical analysis was used to determine localization of DcpS in normal and CRC tissue, western blot analysis for quantification of protein expression and qPCR for mRNA expression in normal and CRC tissue and expression in cell lines after silencing using siRNA. Gene array analysis was used to study regulation of genes after silencing of DcpS. Proliferation was studied using BRDU.RESULTS: DcpS expression was localized to the epithelial cells of both control and cancer tissue. Tumor and paired control tissue samples from 100 patients who underwent surgical resection for primary colorectal adenocarcinomas were utilized. mRNA and protein of DcpS was significantly up-regulated in the patients with CRC and the mRNA level was higher in rectal cancer tissue compared to colon cancer tissue (p < 0.05). Lowest tertile levels of DcpS mRNA in cancer tissue was associated with a decreased cancer-specific survival rate with a hazard ratio (HR) of 4.7 (95% CI=1.02-12.3), independent of disease stage. The low level of DcpS mRNA was a predictor of poorer survival in patients with rectal and disseminated cancer and in patients receiving adjuvant treatment (p < 0.05). After silencing DcpS in Caco-2 cancer cells, altered expression of several genes associated with RNA, cell cycle regulation, alternative splicing and microRNA was observed and resulted in 23% increase in proliferation.CONCLUSIONS: These results indicate that DcpS has potential as a prognostic factor for CRC but further studies in a broader cohort are warranted to evaluate the significance of the findings in the clinic.
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- Li, Xingru, et al.
(författare)
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A modified protein marker panel to identify four consensus molecular subtypes in colorectal cancer using immunohistochemistry
- 2021
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Ingår i: Pathology, Research and Practice. - : Elsevier. - 0344-0338 .- 1618-0631. ; 220
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is a heterogeneous disease with different genetic and molecular backgrounds, leading to a diverse patient prognosis and treatment response. Four consensus molecular subtypes (CMS 1–4) have recently been proposed based on transcriptome profiling. A clinically practical immunohistochemistry (IHC) based CMS classifier consisting of the four markers FRMD6, ZEB1, HTR2B, and CDX2 was then demonstrated. However, the IHC-CMS classifier did not distinguish between CMS2 and CMS3 tumours. In this study, we have applied the proposed transcriptome based and IHC-based CMS classifiers in a CRC cohort of 65 patients and found a concordance of 77.5 %. Further, we modified the IHC-CMS classifier by analysing the differentially expressed genes between CMS2 and CMS3 tumours using RNA-sequencing data from the TCGA dataset. The result showed that WNT signalling was among the most upregulated pathways in CMS2 tumours, and the expression level of CTNNB1 (encoding β-catenin), a WNT pathway hallmark, was significantly upregulated (P = 1.15 × 10−6). We therefore introduced nuclear β-catenin staining to the IHC-CMS classifier. Using the modified classifier in our cohort, we found a 71.4 % concordance between the IHC and RNA-sequencing based CMS classifiers. Moreover, β-catenin staining could classify 16 out of the 19 CMS2/3 tumours into CMS2 or CMS3, thereby showing an 84.2 % concordance with the RNA-sequencing-based classifier. In conclusion, we evaluated CMS classifiers based on transcriptome and IHC analysis. We present a modified IHC panel that categorizes CRC tumours into the four CMS groups. To our knowledge, this is the first study using IHC to identify all four CMS groups.
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| 17. |
- Li, Yifei, et al.
(författare)
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Can Nup88 expression be associated with atypical endometrial hyperplasia and endometrial cancer? A preliminary study
- 2016
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Ingår i: Pathology, Research and Practice. - : ELSEVIER GMBH, URBAN & FISCHER VERLAG. - 0344-0338 .- 1618-0631. ; 212:4, s. 274-278
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Tidskriftsartikel (refereegranskat)abstract
- Background: Nup88 is overexpressed in a number of types of carcinomas and is associated with myometrial invasion, but its exact expression pattern in endometrial cancer and premalignant lesions is unknown. Aims: To evaluate the role of Nup88 in endometrial cancers and atypical endometrial hyperplasia and its clinicopathological significance. Methods: Nup88 expression was examined by immunohistochemistry in samples from 104 endometrial cancers, 21 atypical endometrial hyperplasia lesions, and 40 normal endometria. All samples were from patients who underwent surgery at the First Hospital of Hebei Medical University (Shijiazhuang, China) between April 2006 and December 2009. Nup88 expression was compared between the groups and associations were assessed between Nup88 and clinicopathological characteristics of the subjects. Results: Nup88 expression in cancer (76% of samples) and atypical hyperplasia (91%) was significantly higher compared to normal endometrium (33%, both P < 0.001), but there was no significant difference between endometrial cancer and atypical hyperplasia (P = 0.237). The expression of Nup88 increased significantly with increasing exposure time to estrogen (P = 0.033). Conclusions: Nup88 may be related to the occurrence of endometrial cancers and premalignant lesions. Nup88 might be a useful biomarker for pre-malignant lesions and early-stage endometrial cancer. (C) 2016 Elsevier GmbH. All rights reserved.
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| 18. |
- Marginean, Felicia Elena, et al.
(författare)
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Nuclear expression of pSTAT3Tyr705 and pSTAT3Ser727 in the stromal compartment of localized hormone-naïve prostate cancer
- 2022
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Ingår i: Pathology Research and Practice. - : Elsevier BV. - 0344-0338. ; 232
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Tidskriftsartikel (refereegranskat)abstract
- Background: The signal transducer and activator of transcription 3 (STAT3) is involved in the progression of different tumors including prostate cancer (PCa). The expression of STAT3 in benign and malignant epithelium has been described previously but it has not been described in the stromal compartment. The aim of the present study was to evaluate the nuclear expression and prognostic value of different forms of phosphorylated STAT3 in the stromal compartment of non-cancer and cancer areas of prostatic tissue. Material and methods: Tissue microarray cores from radical prostatectomy of 225 patients with hormone-naïve localized PCa were immunostained for two phosphorylated forms of STAT3, pSTAT3Tyr705 and pSTAT3Ser727. The prognostic value of the expression levels was studied by Cox regression analysis and biochemical recurrence (BCR)-free survival illustrated by Kaplan-Meier curves. Results: Expression of pSTAT3Tyr705 and pSTAT3Ser727 in the stromal compartment of cancer tissue was lower compared with non-cancer areas. In univariable and multivariable Cox regression analysis, expression levels of pSTAT3Tyr705 and STAT3Ser727 showed similar prognostic value as pathological T-stage, Gleason score and surgical margin status. Kaplan–Meier survival analysis showed that low nuclear expression levels of pSTAT3Tyr705 and pSTAT3Ser727 in stromal cells in cancer compartment and in non-cancer areas were related to BCR-free survival. Conclusions: Nuclear expression of pSTAT3Tyr705 and pSTAT3Ser727 in the stromal cells mirrors previous findings in the epithelial component in that it displays prognostic value in men undergoing radical prostatectomy for localized hormone-naïve PCa.
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| 19. |
- Mateoiu, Claudia, et al.
(författare)
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Primary vulvar adenocarcinoma of intestinal type: Report of two cases showing molecular similarity with colorectal adenocarcinoma
- 2024
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Ingår i: PATHOLOGY RESEARCH AND PRACTICE. - 0344-0338 .- 1618-0631. ; 255
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Tidskriftsartikel (refereegranskat)abstract
- Primary vulvar adenocarcinoma is a particularly rare tumor with poorly understood histogenesis and unclear clinical characteristics and prognosis. Vulvar adenocarcinoma of intestinal type (VAIt) is a very uncommon subtype of primary vulvar adenocarcinoma and only 27 cases have been described in the literature in the past. Of these cases, two have been described as human papillomavirus (HPV)-associated VAIt. The current report presents two additional cases of primary VAIt showing variants in the KRAS, TP53, and DPYD genes and no evidence of HPV DNA by real-time polymerase chain reaction (RT-PCR). Next-generation sequencing (NGS) revealed TP53 pathogenic variants in both cases, but only one case had aberrant p53 protein immunohistochemical characteristics. KRAS and DPYD mutations were identified separately in the two cases. Due to their capacity to imitate the spread of more prevalent gastrointestinal carcinomas, these tumors may present diagnostic issues. Additional cases can contribute to a better understanding of the pathophysiology and prognosis of VAIt.
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| 20. |
- Paudel, Keshav Raj, et al.
(författare)
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In vitro anti-cancer activity of a polyherbal preparation, VEDICINALS®9, against A549 human lung adenocarcinoma cells
- 2023
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Ingår i: Pathology, Research and Practice. - : Elsevier. - 0344-0338 .- 1618-0631. ; 250
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Tidskriftsartikel (refereegranskat)abstract
- PurposeNon-small cell lung cancer (NSCLC) is among the leading causes of morbidity and mortality worldwide. Despite the availability of several treatment options, the five-year survival rate of NSCLC is extremely low (<20%). This underlines the necessity of more effective therapeutic alternatives. In this context, plant-derived extracts and bioactive molecules extracted from plants, known collectively as phytoceuticals, represent an extremely variegated source of bioactive compounds with potent anticancer potential. In the present study, we tested the in vitro anticancer activity of a polyherbal preparation, VEDICINALS®9, containing nine different bioactive principles extracted by medicinal plants.MethodsThe anticancer activity of VEDICINALS®9 was investigated by measuring its impact on A549 human NSCLC cell proliferation (MTT assay and trypan blue staining), migration (wound healing assay and transwell chamber assay) and by measuring the impact on the expression of cancer-related proteins (Human XL Oncology Protein Array).ResultsWe show that VEDICINALS®9 at a concentration of 0.2% v/v has potent anticancer effect, significantly inhibiting A549 cell proliferation and migration. Mechanistically, this was achieved by downregulating the expression of proteins involved in cancer cell proliferation (Axl, FGF basic, enolase 2, progranulin, survivin) and migration (Dkk-1, cathepsins B and D, BCL-x, amphiregulin, CapG, u-plasminogen activator). Furthermore, treatment with VEDICINALS®9 resulted in increased expression of the oncosuppressor protein p53 and of the angiogenesis inhibitor endostatin.ConclusionsTaken together, our results provide proof of principle of the potent anticancer activity of the polyherbal preparation VEDICINALS®9, highlighting its enormous potential as an alternative or adjuvant therapy for lung cancer.
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| 23. |
- Schaumann, N., et al.
(författare)
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Lobular neoplasia and invasive lobular breast cancer: Inter-observer agreement for histological grading and subclassification
- 2019
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Ingår i: Pathology Research and Practice. - : Elsevier BV. - 0344-0338. ; 215:11
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Tidskriftsartikel (refereegranskat)abstract
- Lobular neoplasia (LN), invasive lobular breast cancer (ILBC) and related pleomorphic variants represent a distinct group of neoplastic mammary gland lesions. This study assessed the inter-observer agreement of histological grading in a series of ILBC and LN. 54 cases (36x ILBC, 18x LN) were evaluated by 17 observers. 3978 classification calls on various histological features, including nuclear grade, proliferative activity (Ki67 immunohistochemistry, categorical scoring), histological grade and pleomorphism were obtained. Pairwise Cohen's kappa values were calculated and compared between various features and different observer subsets with variable histomorphological experience. In ILBC, pairwise inter-observer agreement for histological grade ranged from poor to almost perfect concordance and was higher in advanced and experienced histopathologists compared with beginners (P < 0.001). Agreement for proliferation (Ki67) ranged from slight to almost perfect concordance and was also higher in advanced and experienced histopathologists (P < 0.001). Considering different features, agreement for proliferation (Ki67) was superior to agreement for histological grade and nuclear grade, even among advanced and experienced histopathologists (P < 0.001). In LN, agreement for B-classification ranged from poor to almost perfect concordance and was higher in advanced and experienced histopathologists (P < 0.001). Considering different features, agreement for proliferation (Ki67 in LN) was superior to subclassification agreement based on conventional features, such as acinar distention and nuclear grade (P < 0.001). In summary, pairwise inter-observer concordance of histological grading of ILBC and LN is dependent on histomorphological experience. Assessment of proliferation by Ki67 immunohistochemistry is associated with favorable inter-observer agreement and can improve histological grading of ILBC as well as LN. © 2019 Elsevier GmbH
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| 24. |
- Stolte, M, et al.
(författare)
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In patients with Helicobacter pylori gastritis and functional dyspepsia, a biopsy from the incisura angularis provides useful diagnostic information
- 2006
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Ingår i: Pathology, Research and Practice. - : Elsevier BV. - 0344-0338 .- 1618-0631. ; 202:6, s. 405-413
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to assess whether the taking of an additional biopsy from the incisura angularis increases the chance of detecting maximal degrees of atrophy and intestinal metaplasia (IM) in patients with Helicobacter pylori gastritis and functional dyspepsia. At entry into a randomised trial, biopsies were taken from 328 patients (mean age 48 years), two from both the gastric antrum and corpus, and one from the incisura angularis, and comparative grading of gastritis variables was carried out. Biopsy material from the gastric antrum, corpus, and the incisura angularis revealed no notable differences in atrophy or an incidence of IM and mucosa-associated lymphatic tissue. However, when the incisura biopsies were classified histologically, 58% contained antral mucosa (AM), 18% corpus mucosa (CM), and 24% intermediate zone mucosa. AM at the incisura was associated with considerably more severe gastritis in both the incisura and antrum (14% atrophy, 20% IM) than in CM of incisura (2% atrophy, 6% IM). Corpus atrophy and IM were rare in the AM group and absent from the CM group. Incisura angularis biopsy in patients with H. pylori gastritis and functional dyspepsia does give additional information regarding the severity of gastritis expected in the corpus and antrum. Antral-type mucosa in the incisura angularis region seems to indicate an increased risk for the development of atrophy and/or IM. (c) 2006 Elsevier GmbH. All rights reserved.
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