scholarly journals Diagnosis of molecular subtypes of colorectal cancer using immunohistochemistry

2021 ◽  
Vol 10 (3) ◽  
pp. 14-20
Author(s):  
D.S. Shvorob ◽  
◽  
T.I. Shevchenko ◽  
R.B. Kondratyk ◽  
◽  
...  

Colorectal cancer ranks third in the morbidity structure among all malignant tumors and includes sporadic and hereditary neoplasms. Cancer genome sequencing has revealed numerous mutation variants that determine the ways colorectal carcinoma progresses. The course, prognosis, and management strategy of the disease vary greatly depending on the subtype of a molecular tumor. This literature review discusses the latest data on the variants of colorectal cancer oncogenesis and presents the phenotypic model classification based on them. Immunohistochemistry (IHC) is suggested for determining the individual tumor characteristics. The article also clarifies the Bethesda panel used to detect microsatellite instability, markers for Lynch syndrome, and a list of IHC markers for determining the phenotypic model of colorectal carcinoma. Keywords: colorectal cancer, phenotypic models, consensus molecular subtypes (CMS), immunohisto-chemistry, Bethesda panel, Lynch syndrome

1999 ◽  
Vol 14 (3) ◽  
pp. 172-177 ◽  
Author(s):  
J.B. Lopez ◽  
G.P Royan ◽  
M.N. Lakhwani ◽  
M. Mahadaven ◽  
J. Timor

The objective of this study was to compare CA 72-4 with CEA and CA 19-9 in gastrointestinal malignancies. CA 72-4 was assayed by radioimmunoassay and CEA and CA 19-9 with the Abbott IMx analyser. The study included 52 patients with gastrointestinal cancer and 20 controls with benign gastrointestinal diseases. The 52 cases showed marker sensitivities of 39%, 49% and 35% for CA 72-4, CEA and CA 19-9, respectively, and 64% when the markers were combined. Marker expression in serum was highest in colorectal carcinoma followed by gastric and esophageal carcinoma. The sensitivities of the individual markers in colorectal, gastric and esophageal carcinomas, respectively, were: CA 72-4, 56%, 32% and 18%; CEA, 83%, 33% and 18%; CA 19-9, 53%, 25% and 18%. The sensitivity of the three markers in combination was 89%, 50% and 46% in colorectal, gastric and esophageal cancer, respectively. The specificity of CA72-4, CEA and CA 19-9 was 100%, 72% and 86%, respectively. However, CA 72-4 is not a useful a marker for gastrointestinal cancers because of its poor sensitivity. CEA, which had the best overall sensitivity and a reasonable specificity, was the most useful single marker, especially for colorectal cancer. Whereas the single markers were not useful in gastric and esophageal cancer, the combination of the three may be.


2006 ◽  
Vol 53 (2) ◽  
pp. 133-141
Author(s):  
Miroslav Milicevic ◽  
Predrag Bulajic ◽  
Marinko Zuvela ◽  
Zoran Raznjatovic ◽  
Nebojca Lekic ◽  
...  

Aim: To review and discuss the current strategies and controversies in the surgical management of colorectal cancer liver metastases. Methods: An analysis of indications, contraindications and scoring systems and concepts for expanding the indications for resection are discussed. The findings and discussion are related to our own experience, especially with radiofrequency assisted liver resection for colorectal cancer liver metastases. Results: Resection is the only management strategy that can potentially cure the patient. Certain controversies still exist, such as contraindications for surgery, timing of treatment of synchronous metastases, significance of extra-hepatic disease etc. Strategies that can improve respectability are discussed. Parenchyma oriented, tissue sparing surgery facilitates reresection should it become necessary. Conclusion: The management of colorectal cancer liver metastases is still a confusing issue for general oncologists and general surgeons. A multidisciplinary approach that tailors the management strategy to the individual patient is the only option that provides optimal results for patients with advanced disease.


2021 ◽  
Vol 25 (2) ◽  
pp. 544-550
Author(s):  
Jalal Jalal ◽  
Zheen Othman ◽  
Payman Anwar

Background and objective: Colorectal cancer is a heterogeneous malignancy characterized by a wide range of genetic and epigenetic alterations. Clusterin is a heterodimeric glycoprotein widely expressed in a variety of tissues and secreted in many body fluids. Increased clusterin expression has been reported in the normal colonic mucosa, benign polyps, and colorectal carcinoma. This study aimed to detect the frequency of the clusterin immunoexpression in colorectal carcinoma and determine its association with some clinicopathological parameters. Methods: Sixty formalin-fixed paraffin-embedded sections of colorectal adenocarcinoma were obtained and randomly selected from the histopathology laboratory at Rizgary Teaching Hospital and some private histopathology laboratories in Erbil city over two years between December 2016 and December 2018. All patients had been diagnosed to have primary colorectal adenocarcinoma and had undergone surgery. The clinicopathological characteristics of the tumors were revised, and the specimens were analyzed immunohistochemically using anticlusterin mouse monoclonal antibody. Results: Twenty eight cases (46.6%) were labeled as clusterin positive, while 32 cases (53.4%) were negative for clusterin expression. Clusterin expression was significantly associated with the tumor type (Non-mucinous) (P = 0.01) and tumor grade (well to moderately differentiated) (P = 0.03). At the same time, no significant association was found between clusterin immunoexpression and other clinicopathological characteristics like age, gender, tumor site, and tumor stage. Conclusion: Our study indicated that clusterin is overexpressed in some colorectal carcinomas and is significantly associated with histological type and grade. These results suggest that clusterin may play a role in colorectal carcinogenesis. Further studies are required to understand the possible mechanism of clusterin association with carcinogenesis and cancer progression. Keywords: Colorectal cancer; Clusterin; Immunohistochemistry.


2021 ◽  
Author(s):  
jingfeng chen ◽  
Yi-shuo Wang ◽  
Chuan Cheng ◽  
Li-ping Yan ◽  
Peng Gao ◽  
...  

Abstract Background: Multiple primary colorectal cancers (MPCC) includes synchronous colorectal carcinoma (SC) and metachronous colorectal carcinoma (MC), which are defined as multiple malignant colorectal tumors that occur simultaneously or heterochrony. Comparing to isolate colorectal cancer, the incidence of SC is still rare. At present, there are few literatures describing the cases and reviews of SC. Case presentation: Here, we present three cases of SC. The first patient was admitted to our hospital because of a 5-month history of abdominal pain associated with difficult defecation. PET-CT revealed that a mass lesion of the splenic flexure of colon and another mass in sigmoid. Colonoscopy demonstrated double lesions in splenic flexure and sigmoid. Then we performed traditional open subtotal colon resection. Postoperative pathology confirmed that there are malignant characteristics of the double lesions. Another patient was suffered from with dizziness and fatigue for more than 2 years. Abdominal contrast-enhanced CT shows irregular thickening of the ascending colon wall and colonoscopy reveals that there is a tumor in rectum and many polyps in sigmoid. Then we underwent radical resection of rectal cancer and right colon cancer in a laparoscopic operation. Postoperative pathology confirmed moderately differentiated adenocarcinoma of the rectum and ascending colon. The third patient had hematochezia for 1 year. Both rectal magnetic resonance imaging (MRI) and colonoscopy showed that there are two lesions in the rectum, and conventional laparoscopic APR surgery was performed. Postoperative pathology confirmed malignant tumors in the rectum respectively. The mini review summed up the main points about prevalence, clinical manifestation, diagnosis, pathological, treatment and molecular mechanism features of SC based on current literature, which probably has significant distinctions with solitary tumors. Conclusions: Compared with isolated colorectal cancer, SC usually has a low stage,grade and incidence, but the age, sex and location is still a controversial issue. Colonoscopy and surgery are considered to be the best diagnosis and treatment method for SC. At present, serrated adenoma, hyperplastic polyp, ulcerative colitis and Crohn's disease are considered to be closely related to SC. MSI and gene mutation are two molecular mechanisms that lead to SC.


2021 ◽  
Vol 20 (1) ◽  
pp. 115-122
Author(s):  
S. V. Vtorushin ◽  
S. S. Naumov ◽  
I. V. Stepanov ◽  
L. E. Sinyansky ◽  
S. G. Afanasyev

The purpose of the study was to analyze and summarize data regarding a significance of PD -L1 expression in various molecular subtypes of colorectal cancer.Material and Methods. A systemic literature search was conducted in the electronic databases Medline, Cochrane Library, Elibrary, PubMed. Of identified and reviewed 201 full-text articles, we included data from 47 studies.Results. The literature review described the features of the molecular genetic classification of colorectal cancer and revealed the key characteristics of each of the molecular subtypes of this disease. Much attention was paid to the molecular mechanisms of anti-PD -1/PD -L1 therapy. The main problems associated with the standardization of methods for pathomorphological assessment of the expression of this marker and the difficulties of its interpretation in colorectal carcinomas were outlined.Conclusion. Analysis of the literature revealed problems associated with the assessment of PD -L1 expression in colorectal cancer, in particular, with the lack of generally accepted methods for interpreting research results and standardizing methods for pathomorphological diagnosis of malignant tumors of this localization. Further studies are needed for introducing the molecular genetic classification of colorectal carcinomas into a wide clinical practice and personalizing the approach to therapy of this disease.


2008 ◽  
Vol 31 (4) ◽  
pp. 12
Author(s):  
A J Hyde ◽  
D Fontaine ◽  
R C Green ◽  
M Simms ◽  
P S Parfrey ◽  
...  

Background: Lynch Syndrome is an autosomal dominant trait that accounts forapproximately 3% of all cases of colorectal cancer (CRC). It is caused by mutations in DNA mismatch repair (MMR) genes, most commonly MLH1 or MSH2. These MMR defects cause high levels of microsatellite instability (MSI-H) in the tumours. MSI testing of all CRCs to identify potential Lynch Syndrome cases is not practical, so the Bethesda Guidelines, which use clinical and pathological features, were created to identify those tumours most likely to be MSI-H^1. In 2007 Jenkins et. al. created MsPath, a tool based on the pathological features described in the rarely used 3^rd Bethesda criterion, to improve prediction of MSI-H tumours among CRC cases diagnosed before age 60 years^2. Methods: We collected a population-based cohort of 716 CRC cases diagnosed before age 75 years in Newfoundland. For each of these cases we collected family history, performed MSI analysis, and scored a number of pathological features for the purpose of evaluating the accuracy of the Bethesda Criteria and MsPath at predicting MSI-H tumours. Results: Our work validates the MsPath tool in the Newfoundland population for the same age group used to create the tool. We found it identified MSI-H cases with a sensitivity of 95% and specificity of 35% in our population of CRCcases diagnosed before age 60 years (n=290). We also tested this tool on our older population of CRCcases, diagnosed at ages 60 to 74 years (n=426). We found it to be at least as predictive in this population,with a sensitivity of 95% and a specificity of 42%. We then used our entire cohort (N=716) to compare MsPath with the other Bethesda criteria.Bethesda criteria 1, 2, 4 and 5 together predicted MSI-H cases with a sensitivity of 67% and a specificity of 51%. MsPath was better at identifying these cases, with a sensitivity of 95% and a specificity of 39%. Conclusions: We conclude that MsPath can be extended to include patients diagnosed with CRC before age 75 years. As well, we have found that MsPath is a better predictive tool than the Revised Bethesda Guidelines for identifying MSI-H cases within a population-based setting of colorectal cancer. References: 1. Umar, A. et. al. J Natl Cancer Inst 2004;96:261-8 2.Jenkins, M.A. et. al. Gastroenterology 2007;133:48-56


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