scholarly journals AWE-02 Morphological and molecular markers for coexistent adenocarcinoma in low-grade dysplastic areas of high-grade colorectal adenomas

2019 ◽  
Author(s):  
Andrew Emmanuel ◽  
Salvador Diaz-Cano ◽  
Shraddha Gulati ◽  
Savvas Papagrigoriadis ◽  
Bu Hayee ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Colorectal Adenomas ◽  
Low Grade ◽  
High Grade

scholarly journals Mutation Profiling of Premalignant Colorectal Neoplasia

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Jakub Karczmarski ◽  
Krzysztof Goryca ◽  
Jacek Pachlewski ◽  
Michalina Dabrowska ◽  
Kazimiera Pysniak ◽  
...  
Keyword(s):  
Cellular Proliferation ◽  
Colorectal Neoplasia ◽  
Copy Number Variant ◽  
Genetic Alterations ◽  
Colorectal Adenomas ◽  
Colorectal Carcinogenesis ◽  
High Grade Dysplasia ◽  
Low Grade ◽  
High Grade ◽  
Allelic Variants

Accumulation of allelic variants in genes that regulate cellular proliferation, differentiation, and apoptosis may result in expansion of the aberrant intestinal epithelium, generating adenomas. Herein, we compared the mutation profiles of conventional colorectal adenomas (CNADs) across stages of progression towards early carcinoma. DNA was isolated from 17 invasive adenocarcinomas (ACs) and 58 large CNADs, including 19 with low-grade dysplasia (LGD), 21 with LGD adjacent to areas of high-grade dysplasia and/or carcinoma (LGD-H), and 28 with high-grade dysplasia (HGD). Ion AmpliSeq Comprehensive Cancer Panel libraries were prepared and sequenced on the Ion Proton. We identified 956 unique allelic variants; of these, 499 were considered nonsynonymous variants. Eleven genes (APC, KRAS, SYNE1, NOTCH4, BLNK, FBXW7, GNAS, KMT2D, TAF1L, TCF7L2, and TP53) were mutated in at least 15% of all samples. Out of frequently mutated genes, TP53 and BCL2 had a consistent trend in mutation prevalence towards malignancy, while two other genes (HNF1A and FBXW7) exhibited the opposite trend. HGD adenomas had significantly higher mutation rates than LGD adenomas, while LGD-H adenomas exhibited mutation frequencies similar to those of LGD adenomas. A significant increase in copy number variant frequency was observed from LGD through HGD to malignant samples. The profiling of advanced CNADs demonstrated variations in mutation patterns among colorectal premalignancies. Only limited numbers of genes were repeatedly mutated while the majority were altered in single cases. Most genetic alterations in adenomas can be considered early contributors to colorectal carcinogenesis.

Immunohistochemical Expression of p53 and Ki67 in Colorectal Adenomas and Prediction of Malignancy and Development of New Polyps

2008 ◽  
Vol 23 (2) ◽  
pp. 89-95 ◽  
Author(s):  
R. Vernillo ◽  
B. Lorenzi ◽  
T. Banducci ◽  
C. Minacci ◽  
C. Vindigni ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Statistical Significance ◽  
Colorectal Adenomas ◽  
Low Grade ◽  
High Grade ◽  
Immunohistochemical Expression ◽  
Ki67 Expression ◽  
P53 Immunoreactivity ◽  
Clinicopathological Variables

The aim of this study was to investigate the immunohistochemical expression of p53 and Ki67 in colorectal adenomas in order to clarify their significance as indicators of malignancy and development of new polyps. Seventy-eight polyps were removed from 51 patients and examined. Twenty-nine patients (56.9%) had adenomas with low-grade atypia (13 of them developed new polyps at 3-year follow-up) and 22 (43.1%) had adenomas with high-grade atypia (6 of them developed new polyps at 3-year follow-up). We tested the association between p53 and Ki67 expression and various clinicopathological variables, and regression analysis was performed to identify the risk factors for malignancy and development of new adenomas. A significant correlation between the grade of atypia and p53 immunoreactivity was observed. Ki67 expression was not related to atypia and no correlation was found between p53 and Ki67 immunoreactivity. Regression analysis showed that size (p=0.0002) and p53 staining (p=0.0111) were the selected factors related to malignant transformation, whereas the number of synchronous primary polyps emerged as the only predictive factor of development of new adenomas, although without statistical significance. The expression of biological markers may be in future added to the currently examined features of polyps; however, further studies are needed to better define their predictive value.

scholarly journals Histopathological features for coexistent invasive cancer in large colorectal adenomatous polyps

BJS Open ◽  
2021 ◽  
Vol 5 (3) ◽  
Author(s):  
A Emmanuel ◽  
A Haji ◽  
S Gulati ◽  
J Moorhead ◽  
S Papagrigoriadis ◽  
...  
Keyword(s):  
Operating Characteristic ◽  
Characteristic Curve ◽  
Colorectal Adenomas ◽  
Histopathological Analysis ◽  
Low Grade ◽  
High Grade ◽  
Invasive Adenocarcinoma ◽  
Histopathological Features ◽  
High Nuclear Grade ◽  
Mitotic Figures

Abstract Background Histopathological features associated with coexistent invasive adenocarcinoma in large colorectal adenomas have not been described. This study aimed to determine the association of histopathological features in areas of low-grade dysplasia with coexistent invasive adenocarcinoma. Methods High-grade lesions (containing high-grade dysplasia or adenocarcinoma) from a cohort of large (at least 20 mm) colorectal adenomas removed by endoscopic resection were subjected to detailed histopathological analysis. The histopathological features in low-grade areas with coexistent adenocarcinoma were reviewed and their diagnostic performance was evaluated. Results Seventy-four high-grade lesions from 401 endoscopic resections of large adenomas were included. In the low-grade dysplastic areas, a coexistent invasive adenocarcinoma was associated significantly with a cribriform or trabecular growth pattern (P < 0.001), high nuclear grade (P < 0.001), multifocal intraluminal necrosis (P < 0.001), atypical mitotic figures (P = 0.006), infiltrative lesion edges (P < 0.001), a broad fibrous band (P = 0.001), ulceration (P < 0.001), expansile nodules (P < 0.001) and an extensive tumour-infiltrating lymphocyte pattern (P = 0.04). Lesions with coexistent invasive adenocarcinoma harboured at least one of these features. The area under the receiver operating characteristic curve (AUROC) for coexistent invasive adenocarcinoma, using frequencies of adverse histopathological factors in low-grade areas, was 0.92. The presence of two or more of these adverse histopathological features in low-grade areas had a sensitivity of 86 per cent and a specificity of 84 per cent for coexistent invasive adenocarcinoma. Conclusion Several histopathological features in low-grade dysplastic areas of adenomas could be predictive of coexistent adenocarcinoma.

scholarly journals The Influence of the Genetic and Immunologic Context in the Development of Colorectal Adenoma: A Case Series Report

2020 ◽  
Vol 33 (5) ◽  
pp. 297
Author(s):  
Diogo Garcia ◽  
Louisa Spaans ◽  
Sara Miranda ◽  
Gilza Gonçalves ◽  
Joana Reis ◽  
...  
Keyword(s):  
Immune Cell ◽  
Immune Escape ◽  
Immune Surveillance ◽  
Case Series ◽  
Colorectal Adenomas ◽  
Low Grade ◽  
High Grade ◽  
Immune Microenvironment ◽  
Major Step ◽  
Cell Counts

Introduction: Overcoming immunosurveillance is a major step in the progression of many types of tumors. Several immune escape strategies have been identified, including immunoediting and the establishment of an immune suppressive microenvironment. The aim of the present study was to determine whether the hereditary or sporadic context has any influence in the relationship between immune surveillance and tumor development, using sporadic and familial adenomatous polyposis related colorectal adenomas as a model.Material and Methods: The immune tumor-infiltrating cells of a total of 58 low-grade and 18 high-grade colorectal adenomas were examined and compared, using immunostaining for CD3, CD4, CD8, CD57, CD68 and FoxP3.Results: FoxP3 and CD68 counts were significantly higher in sporadic low-grade dysplasia (p = 0.0003 and p = 0.0103, respectively),and FoxP3 and CD4 counts were found to be significantly higher in high-grade sporadic dysplasia (p = 0.0008 and p = 0.0018, respectively)when compared with corresponding lesions in patients with familial adenomatous polyposis.Discussion: This study suggests that the immune microenvironment of sporadic and hereditary lesions is different. Sporadic lesions contain a higher number of immune suppressive Treg cells, which suggests a stronger immune selective pressure. In contrast, hereditarylesions seem to benefit from a more tolerant immune microenvironment, allowing for the development of lesions with lower immune cell infiltration.Conclusion: This study shows that sporadic lesions harbor higher tumor-infiltrating immune cell counts, which might reflect a higher immune tolerance towards hereditary lesions.

scholarly journals Metabolic syndrome is a risk factor for colorectal adenoma and cancer: a study in a White population using the harmonized criteria

2019 ◽  
Vol 12 ◽  
pp. 175628481986783 ◽  
Author(s):  
Angelo Milano ◽  
Maria Antonia Bianco ◽  
Luigi Buri ◽  
Livio Cipolletta ◽  
Enzo Grossi ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Risk Factor ◽  
Colorectal Adenomas ◽  
High Risk Population ◽  
Low Grade ◽  
High Grade ◽  
Screening Programs ◽  
In Situ Carcinoma ◽  
Laterally Spreading Tumors

Background: Metabolic syndrome (MetS) has been associated with colorectal adenomas and cancer. However, MetS definitions have changed over time, leading to a heterogeneity of patients included in previous studies and a substantial inextensibility of observations across time or eastern and western populations. Our aim was to evaluate the association of ‘harmonized’ criteria-defined MetS and its individual components with colorectal neoplasia and cancer in a western population. Methods: In this multicenter, cross-sectional study, we prospectively evaluated consecutive outpatients who underwent open-access colonoscopy over a 3-month period. MetS was diagnosed according to the 2009 ‘harmonized’ criteria. Results: Out of 5707 patients enrolled, we found 213 cancers (3.7%), 1614 polyps (28.3%), 240 nonpolypoid lesions (4.2%), 95 laterally spreading tumors (1.6%). Polyps presented histological low-grade dysplasia in 72.9% of samples, while in 9.8%, high-grade dysplasia or in situ carcinoma was present; dysplasia rates for nonpolypoid lesions were 66.2% (low-grade) and 2.9% (high-grade/ in situ carcinoma), while for laterally spreading tumors, 29.6% and 37%, respectively. Overall, MetS prevalence was 41.6%. MetS correlated with both adenomas [odds ratio (OR): 1.76, 95% confidence interval (CI) 1.54–2.00] and cancer (OR: 1.92, 95% CI 1.42–2.58). MetS was the only risk factor for such colonic lesions in subjects younger than 50 years. For all colonic neoplasia, we found MetS and not its individual components to be significantly associated. Conclusions: MetS is risk factor for cancer and adenoma in Whites, especially when younger than 50 years. MetS patients might be considered as a high-risk population also in colorectal cancer screening programs.

378 Analysis of Molecular Markers and Volumetric Extent of Resection on Survival for Insular Gliomas

Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 289-290
Author(s):  
Chikezie Eseonu ◽  
Karim ReFaey ◽  
Gugan Raghuraman ◽  
Alfredo Quiñones-Hinojosa
Keyword(s):  
Molecular Markers ◽  
Survival Rate ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Idh1 Mutation ◽  
Low Grade ◽  
High Grade ◽  
Free Survival ◽  
Low Grade Gliomas

Abstract INTRODUCTION Insular gliomas are challenging tumors to surgically resect due to the anatomy surrounding them. This study evaluates the role of extent of resection (EOR) and molecular markers on surgical outcome and survival for insular gliomas. METHODS Seventy-four patients who had undergone an initial resection for an insular glioma by the same surgeon from 2006 to 2016 were analyzed. Low(grade II) and high(grade III/IV) grade gliomas were analyzed for the prognostic role of volumetric EOR and molecular markers (IDH1 mutation, 1p/19q codeletion) on patient survival outcomes. RESULTS >The cohort includes 25 low grade gliomas (LGGs) patients(33.8%), and 49 high grade glioma(HGGs) patients(66.2%). The median EOR was 91.7% (range 10–100%). New permanent postoperative deficits were found in 2.7% of patients. LGG patients with a = 90% EOR had a 5-year survival rate of 100% and patients with a <90% EOR had 5-year survival of 80%. HGG patients with a = 90% EOR had a 2-year survival rate of 83.7%, and patients with a <90% EOR had 2-year survival of 43.8%. For LGGs, accounting for EOR, IDH1 mut, 1p/19 codeletion, the EOR was predictive of OS(P = 0.017), progression free survival (PFS, P = 0.039), and malignant progression free survival (MPFS, P = 0.014), while the 1p/19q co-deletion was predictive for PFS (P = 0.014). For HGGs, the EOR was predictive of OS (P = 0.020) and PFS(P = 0.024). Preoperative tumor volume was a factor that most significantly affected the EOR for insular gliomas (R2 = 0.053, P = 0.048). CONCLUSION Extensive resections of insular gliomas can be achieved with low morbidity and can improve OS and PFS. In this series of low-grade gliomas, EOR was associated with longer MPFS, and the 1p/19q co-deletion was predictive of PFS.

Klinische Wertigkeit der Positronen-Emissions-Tomographie (PET) bei onkologischen Fragestellungen: Ergebnisse einer interdisziplinären Konsensuskonferenz

1996 ◽  
Vol 35 (02) ◽  
pp. 42-52 ◽  
Author(s):  
R. Bares ◽  
U. Bull ◽  
A. Guhlmann ◽  
E. Moser ◽  
M. F. Wannenmacher ◽  
...  
Keyword(s):  
Low Grade ◽  
High Grade ◽  
Klinische Anwendung ◽  
Wissenschaftliche Studien

Zusammenfassung Ziel: Es ist das Ziel der vorliegenden Arbeit, an Hand bisher publizierter Studienergebnisse eine Beurteilung des klinischen Stellenwertes von PET in der Onkologie zu erarbeiten. Methoden: Im Rahmen einer interdisziplinären Konferenz mit namhaften Experten wurde eine Wertung des gegenwärtigen Stands von PET in der Onkologie an Hand der in der Literatur dokumentierten Studienergebnisse erarbeitet. Angestrebt wurde eine differenzierte Bewertung von PET für die klinische Anwendung in fünf Klassen (1a, 1b, 2a, 2b, 3) von »angemessen« (1a), »akzeptabel« (1b), »hilfreich« (2a), »noch keine Bewertung möglich« (2b), »ohne Nutzen« (3). Ergebnisse: Für den klinischen Einsatz in der Onkologie ist 2-F18-Fluorodeoxyglukose (FDG) das Radiopharmakon der Wahl. PET ist klinisch in der Patientenversorgung zur Rezidivdiagnostik von high-grade Gliomen (FDG), low-grade Gliomen (C-11 Methionin oder F-18 Tyrosin), für die Dignitätsdiagnostik des peripheren Lungenrundherdes bei Risikopatienten sowie für die Diagnostik des Pankreaskarzioms indiziert (Indikation 1a). PET kann in der Patientenversorgung bei folgenden Indikationen (1b) eingesetzt werden: »low-grade« Gliome, Suche nach unbekanntem Primärtumor bei Kopf-Hals-Tumoren, Rezidivdiagnostik des nicht kleinzelligen Bronchialkarzinoms sowie des Rektumkarzinoms, Lymphknotenstaging beim nicht kleinzelligen Bronchial-Karzinom, Pan-kreas-Karzinom, muskelinvasiven Blasen-Karzinom und Hoden-Karzinom. Staging bei M. Hodgkin (Stad. I/II versus III), frühe Therapiekontrolle bei Resttumor und Rezidivdiagnostik bei M. Hodgkin und hochmalignen Non-Hodgkin-Lymphomen, Lymphknoten-Staging und Fern-metastasensuche beim malignen Melanom (Breslow >1,5 mm), Lymphknoten- und Fernmetastasen-Nachweis beim Schilddrüsen-Karzinommit erhöhtem hTg und nicht radiojodspeichernden Metastasen. Zahlreiche weitere Indikationen zeichnen sich bereits jetzt ab, sind jedoch noch weniger gut durch wissenschaftliche Studien belegt. Für die meisten Indikationen außerhalb wissenschaftlicher Studien ist eine individuelle Kosten-Nutzen-Betrachtung durch den verantwortlichen Arzt geboten. Schlußfolgerungen: Die metabolische Bildgebung von PET besitzt für eine Vielzahl onkologischer Fragestellungen prinzipielle Vorteile gegenüber der anatomisch-morphologisch orientierten Schnittbilddiagnostik. Für die klinische Indikationsstellung ist allerdings eine differenzierte Betrachtung der spezifischen Leistungsfähigkeit von PET geboten.

CD133/CD166/Ki-67 Triple Immunouorescence Assessment for Putative Cancer Stem Cells in Colon Carcinoma*

2014 ◽  
Vol 23 (2) ◽  
pp. 161-170 ◽  
Author(s):  
Claudiu Margaritescu ◽  
Daniel Pirici ◽  
Irina Cherciu ◽  
Alexandru Barbalan ◽  
Tatiana Cârtâna ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Colon Cancer ◽  
Cancer Stem Cells ◽  
Colon Carcinoma ◽  
Sodium Dodecyl ◽  
High Grade Dysplasia ◽  
Early Event ◽  
Low Grade ◽  
High Grade

Background & Aims: Colorectal cancer represents the third most common malignancy and the fourth most common cause of cancer death worldwide. The existence of drug-resistant colon cancer stem cells is thought to be one of the most important reasons behind treatment failure in colon cancer, their existence putatively leading to metastasis and recurrences. The aim of our study was to investigate the immunoexpression patterns of CD133 and CD166 in colon carcinoma, both individually and in combination, assessing their significance as prognostic markers.Methods. A total of 45 retrospective colon adenocarcinoma cases were investigated by enzymatic and multiple fluorescence immunohistochemistry for their CD133 and CD166 expression and colocalization.Results. Both CD133 and CD166 were expressed to different extents in all cancer specimens, with apredominant cytoplasmic pattern for CD133 and a more obvious membranous-like pattern for CD166.Overall, when comparing their reactivity for the tumoral tissue, CD166 expression areas seemed to be smaller than those of CD133. However, there was a direct correlation between CD133 and CD166 expression levels throughout the entire spectrum of lesions, with higher values for dysplastic lesions. Colocalization of CD133/ CD166 was obvious at the level of cells membranes, with higher coeficients in high grade dysplasia, followed by well and moderate differentiated tumours.Conclusions. CD133/CD166 colocalization is an early event occurring in colon tumorigenesis, with thehighest coeficients recorded for patients with high grade dysplasia, followed by well differentiated tumours. Thus, we consider that the coexpression of these two markers could be useful for further prognostic andtherapeutically stratification of patients with colon cancer.Abbreviations: AJCC - American Joint Committee on Cancer; CCD - charge-coupled device camera sensor; CD133 - prominin-1 (PROM1); CD166 - Activated Leukocyte Cell Adhesion Molecule (ALCAM); CRC - colorectal cancer; CSC - cancer stem cells; DAB - 3,3'-diaminobenzidine chromogen; DAPI - 4',6-diamidino- 2-phenylindole; HE - Hematoxylin and eosin staining; HGD - high grade dysplasia; HRP - horseradish peroxidase; LGD - low grade dysplasia; SDS - sodium dodecyl sulfate*Part of this work has been accepted as a poster presentation at the Digestive Disease Week (DDW) meeting, Chicago, IL, USA May 3-6, 2014

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