Relationship among mismatch repair deficiency, CDX2 loss, p53 and E-cadherin in colon carcinoma and suitability of using a double panel of mismatch repair proteins by immunohistochemistry

Sayar, Ilyas; Akbas, Emin Murat; Isik, A. F.; Gökçe, Aysun; Peker, Kemal; Demirtaş, Levent; Gürbüzel, Mehmet

doi:10.5114/pjp.2015.54958

Cited by 13 publications

(17 citation statements)

References 35 publications

(72 reference statements)

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“…The association of RBM3 expression and proliferation assessed by Ki-67 expression was weak, while a significant negative correlation between RBM3 and tumor biomarker p53 was observed, indicating that high RBM3 expression is a favorable prognostic factor. We also found that Ki-67 and p53 were prognostic factors, but were not independent from other clinicopathological parameters in this study, which is consistent with other reports [ 13 , 31 – 33 ]. However, our study revealed that RBM3 is independent of prognostic factors, excluding Lauren grade.…”

Section: Discussionsupporting

confidence: 92%

High RNA-Binding Motif Protein 3 (RBM3) Expression is Independently Associated with Prolonged Overall Survival in Intestinal-Type Gastric Cancer

Jin

Cai

et al. 2017

Med Sci Monit

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BackgroundHigh expression of the RNA-binding motif protein 3 (RBM3) has previously been described as a favorable clinicopathological factor in several cancers, including ovarian cancer, colorectal cancer, prostate cancer, and breast cancer. The aim of this study was to examine the prognostic implications of RBM3 expression in gastric cancer.Material/MethodsImmunohistochemical analysis of RBM3 expression from 123 patients showed that upregulated RBM3 was mainly found in intestinal-type (n=78, case=59) cancer compared to diffuse-type (n=15, case=8) and mixed-type (n=30, case=17). There were no significant differences in RBM3 expression in subgroups of clinicopathological parameters. RBM3 expression was strongly associated with p53 but not with Ki-67. Cox univariate analysis revealed that high RBM3 expression was closely associated with prolonged overall survival time (HR 0.504, 95% CI: 0.300–0.845, P=0.009). Multivariate analysis remained supporting these associations when adjusted for age, sex, tumor size, differentiation grade, TNM stage, lymphatic invasion, and Ki-67 and p53 expression (HR 0.541, 95% CI: 0.308–0.952, P=0.033), where Lauren grade was not included. Lauren grade was the only factor with independent prognostic significance in a model adjusted for all factors. These results were confirmed by Kaplan-Meier analysis.ResultsTherefore, together with the upregulated RBM3 expression observed in intestinal-type of Lauren grade, we suggest that upregulation of RBM3 is partially responsible for the favorable overall survival in cases with intestinal Lauren grade, which is demonstrated by the box diagram and Kaplan-Meier analysis. Our results showed that high RBM3 expression in gastric cancer is mainly found in intestinal-type of Lauren grade and is associated with longer overall survival time.ConclusionWe found that RBM3 is a potential biomarker of good prognosis and deserves further validation.

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Section: Discussionsupporting

confidence: 92%

High RNA-Binding Motif Protein 3 (RBM3) Expression is Independently Associated with Prolonged Overall Survival in Intestinal-Type Gastric Cancer

Jin

Cai

et al. 2017

Med Sci Monit

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“…CDX2 is a transcription factor involved in differentiation and proliferation of intestinal epithelial cells, mainly in the distal part of the intestine. Loss of CDX2 expression was reported to be involved in progression of some sporadic CRCs [35][36][37][38][39].…”

Section:  Introductionmentioning

confidence: 99%

Assessment of mismatch repair deficiency, CDX2, beta-catenin and E-cadherin expression in colon cancer: molecular characteristics and impact on prognosis and survival – an immunohistochemical study

Melincovici

Boșca

Şuşman³

et al. 2021

Rom J Morphol Embryol

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Microsatellite instability (MSI) or the deficiency of mismatch repair (MMR) proteins is one of the molecular pathways of colorectal tumorigenesis and may have important clinical implications in predicting the treatment response. We evaluated the relationship between clinicopathological features and MMR proteins [mutL homologue 1 (MLH1), mutS homologue 2 (MSH2), mutS homologue 6 (MSH6), postmeiotic segregation increased 2 (PMS2)], adhesion molecules (E-cadherin, beta-catenin) and caudal-type homeobox 2 (CDX2) in 31 patients with colon adenocarcinoma, using immunohistochemistry. We also aimed to assess the prognostic value of the studied proteins. MLH1 loss was correlated to PMS2 loss (p=0.006) and MSH2 loss (p=0.023); MSH2 loss was significantly associated to MSH6 loss (p=0.011). Tumors with MSH6 loss, together with tumors with PMS2 loss, covered all the patients with MSI status. We found a significant correlation between MSI tumors and mucinous histological type (p=0.03), but no significant associations with other clinicopathological features or with survival rate. There was a significant correlation between E-cadherin expression and differentiation degree (p=0.018) and between beta-catenin expression and lymph node invasion (p=0.046). No significant association between CDX2 loss and any clinical or pathological features was found (p>0.05). No significant differences were identified in overall survival according to E-cadherin, beta-catenin or CDX2 expression (p>0.05). In our study, PMS2 loss was significantly correlated with CDX2 loss (p=0.03). In conclusion, the molecular analysis of biological markers for colon cancer may be important for patient stratification, in order to select the optimal treatment algorithm. Our results suggest that probably the double panel (MSH6 and PMS2) is enough to detect the MSI status, instead of using the quadruple panel.

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“…It is one of the most common cause of cancer-related death worldwide [2]. Cancer colon, as any cancer is caused by environmental and genetic factors [3]. 75% of cancer colon is sporadic and the remaining 30% has a hereditary contribution [4].…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical Expression of MMR Proteins with Clinicopathological Correlation in Colorectal Cancer in Egypt

Soliman¹,

Morsia²,

Helmy³

2019

Open Access Maced J Med Sci

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BACKGROUND: Microsatellite instability (MSI) is the genetic pathway underlying 15% of sporadic colorectal carcinoma (CRC) and hereditary non-polyposis CRC. MSI-H CRC has a distinct clinicopathological characteristic including excess mucin and signet ring component, proximal colon, Crohn’s like reaction, lymphocytic infiltration, and better survival. AIM: This research aims to screen Egyptian CRC patients for MSI status by IHC testing of expression of the MMR proteins in correlation to its clinicopathological features. MATERIAL AND METHODS: Immunohistochemistry study for mismatch repair proteins (MMR) was done on 115 cases of CRC. Their expressions were assessed and correlated to clinicopathological parameters in an attempt to obtain the most significant predictors of MSI. RESULTS: MSI (low and high) represents 67% of the study cases. The most frequent expression pattern was combined loss of MLH, and PMS2 (38% of MSI) followed by a combined loss of MSH2, and MSH6 (29% of MSI). There was significant correlation of expression pattern of MMR proteins with the laterality, lymphovascular emboli, perineural invasion, grade, T stage, N stage, signet ring component, tumor infiltrating lymphocyte, and peritumoral lesion (0.014, 0.035, 0.012, 0.033, 0.013, 0.000, 0.041, 0.012, and 0.009 respectively). Proximal location (right sided) and lower grade, higher nodal stage, and marked TIL were selected as predictors of MS-H CRC (0.005, 0.031, 0.025, and 0.000 respectively). CONCLUSION: All clinicopathological and histological parameters should be assessed in CRC for the sake of predicting MSI. The optimal approach to MSI evaluation is (IHC) assessment of MMR proteins.

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Relationship among mismatch repair deficiency, CDX2 loss, p53 and E-cadherin in colon carcinoma and suitability of using a double panel of mismatch repair proteins by immunohistochemistry

Cited by 13 publications

References 35 publications

High RNA-Binding Motif Protein 3 (RBM3) Expression is Independently Associated with Prolonged Overall Survival in Intestinal-Type Gastric Cancer

High RNA-Binding Motif Protein 3 (RBM3) Expression is Independently Associated with Prolonged Overall Survival in Intestinal-Type Gastric Cancer

Assessment of mismatch repair deficiency, CDX2, beta-catenin and E-cadherin expression in colon cancer: molecular characteristics and impact on prognosis and survival – an immunohistochemical study

Immunohistochemical Expression of MMR Proteins with Clinicopathological Correlation in Colorectal Cancer in Egypt

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