scholarly journals Clinicopathological, Immunohistochemical, and PMS2 Gene Expression Profiling of Patients with Sporadic Colorectal Cancer

2021 ◽  
Vol 24 (2) ◽  
pp. 86-93
Author(s):  
Maryam Mousavi ◽  
Mohammad Taghi Goodarzi ◽  
Seyed Mehrdad Kassaee ◽  
Ali Jafari Heidarloo ◽  
Mojtaba Fathi

Background: The DNA mismatch repair (MMR) system is one of the molecular pathways involved in colorectal cancer (CRC) carcinogenesis that consists of several genes, including MLH1 (MutL homolog 1), MSH6 (MutS homolog 6), MSH2 (MutS homolog 2), and MSH3 (MutS homolog 3). The protein encoded by PMS2 (post-meiotic segregation 2) is also essential for MMR. Here, we address the correlation between immunohistochemical and transcriptional expression of PMS2 with the tumor grade and clinical stage of non-hereditary/sporadic CRC disease. Methods: This study retrospectively analyzed 67 colorectal resections performed for 38 male and 29 female patients. Random biopsies were taken by a gastroenterologist from patients referring to three hospitals in the cities of Zanjan, Urmia and Qazvin (Iran) during 2017-2019. All specimens were examined and classified for localization of tumor, pathological stage and grade. The PMS2 protein expression was studied immunohistochemically and analysis of mRNA expression was performed in the same tissue sections. Results: Immunohistochemistry and quantitative real-time polymerase chain reaction (PCR) analysis showed a decrease in PMS2 expression compared with paracancerous tissue (P<0.001), which correlated with tumor stage. In addition, reduced PMS2 expression was correlated with the tumor differentiation grade, underlining a connection between downregulation of PMS2 and progression of CRC. Comparing the PMS2 mRNA levels in different groups showed the following results: 0.92 ± 0.18 in patients with Stage I CRC tumor, 0.86 ± 0.38 in Stage Ⅱ, 0.50 ± 0.29 in Stage Ⅲ, and 0.47 ± 0.23 in Stage Ⅳ. Conclusion: These findings suggest that PMS2 may provide a potential reliable biomarker for CRC classification by combined immunohistochemical and mRNA analysis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14098-e14098
Author(s):  
Hongliu Sun ◽  
Ashleigh M. Kussman ◽  
Carol Freeman ◽  
Judy Meredith ◽  
Kenneth Hensley ◽  
...  

e14098 Background: Neuropilin 2 (NRP2) is a transmembrane glycoprotein, non-associated with kinase domains, implicated in neovascularization and metastasis of colon cancer. NRP2 has been proposed as a molecular marker for targeted cancer therapy based on its multiple functions in cancer promotion. NRP2 signaling pathway and its expression have been demonstrated in many carcinomas. To the best of our knowledge, no description of the immunohistochemical staining pattern of NRP2 in colon cancer has been published in the English medical literature. The aim of this study is to investigate the NRP2 labelilng pattern in colon cancer and correlate it with tumor stage. Methods: Tumor sections from 35 randomly selected colectomy specimens with colorectal cancer collected during the last three years were retrieved from the University of Toledo Medical Center Department of Pathology archival material. Formalin fixed, paraffin embedded, 4 μm tissue sections containing invasive tumor were immunolabeled with a commercial antibody against NRP2, using a Ventana Benchmark LT automated instrument. Randomized, immunolabeled colon cancer tissue sections were blindly reviewed by two pathologists. Cytoplasmic and nuclear expression of NRP2 by tumor cells was graded as negative (no staining), focal (staining in <50% of cells), and diffuse (staining in ≥ 50% of cells). Adjacent benign colonic mucosa was used as an internal control. Results: No T1 or T2 tumor displayed diffuse nuclear labeling for the NRP2 epitope. In contrast, 13/20 T3 tumors (65%) and 4/4 T4 tumors (100%) displayed diffuse nuclear labeling. The association of diffuse nuclear NRP2 labeling with tumor grade was highly statistically significant (p=0.0055 by Chi-squared test). In contrast to nuclear labeling, cytoplasmic staining was observed in all stages and varied from negative to diffuse, but demonstrated no significant correlation with stage. Conclusions: This pilot study on colon cancer specimens suggests that diffuse nuclear immunolabeling of neuropilin-2 is indicative of a higher tumor stage. This finding suggests a potential use for this marker as a prognostic indicator for colon cancer in small biopsy samples.


2004 ◽  
Vol 22 (13) ◽  
pp. 2623-2634 ◽  
Author(s):  
Georgia Bardi ◽  
Claus Fenger ◽  
Bertil Johansson ◽  
Felix Mitelman ◽  
Sverre Heim

Purpose To investigate the prognostic value of the overall karyotypic features and specific chromosome aberrations in colorectal cancer (CRC). Patients and Methods Cytogenetic features of 150 primary CRCs investigated at the time of surgery were correlated with patient survival by univariate and multivariate analyses, using classical clinicopathologic parameters as covariates. Results In univariate analysis, in addition to tumor grade and clinical stage, structural aberrations as well as rearrangements of chromosomes 8 and 16 were significantly correlated with shorter overall survival. Karyotypic complexity, rearrangements of chromosomes 8 and 16, and loss of chromosome 4 were significantly correlated with shorter disease-free survival. In multivariate analysis, in addition to tumor grade, the type of chromosome aberrations (structural or numerical), ploidy, and loss of chromosome 18 came across as independent prognostic factors in the group of all patients. In the subset of patients with stage I and II carcinomas, none of the clinicopathologic variables could independently predict patient survival, whereas the presence of structural chromosomal aberrations was the only independent predictor of poor prognosis. In the subset of patients with stage III carcinomas, the presence of structural changes of chromosome 8 was a stronger independent predictor of prognosis than was tumor grade. Conclusion Cytogenetic tumor features are valuable predictors of prognosis in CRC patients. The tumor karyotype should therefore be taken into account in the clinical management of patients with this disease, especially for patients having cancers of the early or intermediate stages I, II, and III.


Author(s):  
Melika Kooshki Forooshani ◽  
Amir Hosein Jafarian ◽  
Leila Takallou ◽  
Nema Mohamadian Roshan

Background<br />Gastric carcinoma (GC) is the most common non-skin malignancy in Iranian men and the second leading cause of cancer-related mortality. Invasion and metastasis are considered as the major causes of cancer-related morbidity and mortality. Proteinases such as matrix metalloproteinases play an important role in tumor progression and mediating extracellular matrix remodeling. CD10 is a 90-110kd cell surface zinc-dependent metalloproteinase and there is evidence that this membrane protein may facilitate invasion and/or metastasis of tumoral cells. The objective of this study was to determine the frequency of CD10 expression in the stromal cells of GC and determine its relationship with survival and clinicopathological factors. <br /><br />Methods<br />A cross-sectional study was performed involving 50 patients with histopathologic diagnosis of GC. CD10 expression was determined by immunohistochemistry (IHC). Survival of the patients as well as the grade and stage of the tumors and demographic variables were documented. The Kaplan-Meier test was used for data analysis.<br /><br />Results<br />Stromal CD10 was detected in 46% of the GC stromal cells. No immunoreactivity was identified in the stromal cells of normal adjacent tissue. Stromal CD10 expression in gastric carcinoma did not correlate with the age and gender of the cases as well as the size and location of the tumor, and lymph node involvement but correlated with tumor stage (p=0.01), tumor grade(p=0.01) and patients’ survival (p=0.02). <br /><br />Conclusion<br />Stromal CD10 expression is correlated with tumor differentiation, clinical stage and survival in GC. CD10 expression could be considered as a negative prognostic factor for gastric carcinoma.


2008 ◽  
Vol 74 (10) ◽  
pp. 973-976 ◽  
Author(s):  
Benjamin Karsten ◽  
Justin Kim ◽  
Justin King ◽  
Ravin R. Kumar

Colorectal cancer (CRC) is a disease primarily affecting an older population. The incidence of CRC in young patients has been rising. The purpose of this study was to evaluate the characteristics of CRC in an ethnically diverse, young population. Two groups of patients with CRC (40 years old or younger and 60 years old or older) treated from 1998 to 2005 were retrospectively evaluated. Forty-one young patients with CRC were identified. Hispanics constituted 51 per cent of the young population. Forty-four per cent of the lesions were right-sided in the young group compared with 21 per cent in the older group (P = 0.004). Advanced tumor stage (T3 and T4) was noted in 87.8 per cent of the young and 63 per cent of the older patients (P = 0.002; OR, 4.08). Poorly differentiated tumor grade was more common in young patients (P = 0.003) as well as mucinous/signet ring characteristics (P = 0.005). Young patients had an increased likelihood of a family history (P = 0.0001). Operative intervention and survival were similar for the two groups. Our study confirms, in an ethnically diverse young population, that CRC tends to be advanced stage, aggressive, and frequently nonoperable at the time of diagnosis. It is important for physicians to recognize the poor outcome of CRC in a younger population and consider an aggressive approach to diagnosis and early treatment.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4126-4126 ◽  
Author(s):  
K. Öhrling ◽  
D. Edler ◽  
M. Hallström ◽  
M. Karlberg ◽  
P. Ragnhammar

4126 Background: Microsatellite instability (MSI) is the hallmark of a defective DNA mismatch repair (MMR) and occurs in 10- 20 % of sporadic colorectal cancer (CRC). The loss of the MLH1 protein is the cause of MSI in almost all sporadic colorectal MSI tumours. The second most common protein to be lost is MSH2. There is evidence that MSI is a prognostic factor in CRC. The role of MSI status as a predictive factor of benefit from adjuvant 5-fluorouracil (5-FU) based chemotherapy is controversial. Methods: Monoclonal antibodies that recognize the mismatch repair protein by immunohistochemistry (IHC) have been commercially available for several years. Previous reports have found a strong correlation between MMR results obtained by immunohistochemical and genetic analysis. This study included 1006 CRC patients (488 Stage II and 518 Stage III) with a median follow-up of 5 years. The patients were included in Nordic trials randomised between surgery alone and surgery plus adjuvant 5-FU. The MMR status was retrospectively assessed on paraffin-embedded formalin-fixed samples using IHC. Results: One hundred fifty seven patients (15.6 %) showed a loss of MMR protein expression (139 MLH1 negative, 15 MSH2 negative and 3 MLH1+MSH2 negative) and were classified as MMR protein negative. A normal MMR protein expression was found in 851 patients who were defined as MMR protein positive. The median overall survival (OS) was 84 months (range 2–181 months). MMR protein expression was a significant prognostic marker in the entire study group where a better OS was seen among patients with MMR protein negative carcinomas compared to patients with MMR protein positive tumours (p=0.005). In multivariate analysis the MMR protein expression was significantly associated with OS, (hazard ratio for death, 0.67 [95 per cent confidence interval, 0.38 to 0.96]; p=0.008). However, in this study the MMR status did not predict response to 5-FU adjuvant chemotherapy. Conclusions: This study reveals that immunohistochemical analysis of MLH1 and MSH2 expression can yield important prognostic information but is not a predictive factor in sporadic CRC. No significant financial relationships to disclose.


Author(s):  
Mark Basik ◽  
Daniel L. Stoler ◽  
Konstantinos C. Kontzoglou ◽  
Miguel A. Rodriguez-Bigas ◽  
Nicholas J. Petrelli ◽  
...  

2020 ◽  
Vol 52 (10) ◽  
pp. 1188-1194 ◽  
Author(s):  
Daniela Pugliese ◽  
Alessandro Armuzzi ◽  
Federica Castri ◽  
Roberta Benvenuto ◽  
Antonella Mangoni ◽  
...  

Author(s):  
Fabiola Pabst BREMER ◽  
Nicolau Gregori CZECZKO ◽  
Luiz Martins COLLAÇO ◽  
Letícia Elizabeth Augustin Czeczko RUTZ ◽  
Guilherme GIONEDIS ◽  
...  

ABSTRACT Background: Colorectal cancer (CRC) is one of the most common types of cancer in the world. Over time, intestinal epithelial cells undergo mutations that may lead to proliferative advantage and the emergence of cancer. Mutations in the beta-catenin pathway are amongst those described in the development of CRC. Aim: To verify the existence of a relation between the presence of Wnt3, beta-catenin and CDX2 in colorectal cancer samples and clinical outcomes such as disease progression or death. Method: Wnt3a, beta-catenin and CDX2 immunohistochemistry was performed on CRC tissue microarray samples (n=122), and analysis regarding the relation between biomarker expression and disease progression or death was performed. Results: No significant difference was found between the presence or absence of CDX2, beta-catenin or Wnt3a expression and clinical stage, tumor grade, disease progression or death. Conclusion: CDX2, beta-catenin and Wnt3a are not useful to predict prognosis in patients with CRC.


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