Prognostic implications ofBAX andTGFBRII mutations in colon cancers with microsatellite instability

2002 ◽  
Vol 35 (4) ◽  
pp. 368-371 ◽  
Author(s):  
Wade S. Samowitz ◽  
Karen Curtin ◽  
Susan Neuhausen ◽  
Donna Schaffer ◽  
Martha L. Slattery
Keyword(s):  
Microsatellite Instability ◽  
Colon Cancers ◽  
Prognostic Implications

Microsatellite Instability as a Predictor of Outcomes in Colorectal Cancer in the Era of Immune-Checkpoint Inhibitors

2021 ◽  
Vol 22 ◽  
Author(s):  
Csongor György Lengyel
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Immune Checkpoint ◽  
Predictive Value ◽  
Checkpoint Inhibitors ◽  
Tumor Infiltrating Lymphocytes ◽  
Primary Objective ◽  
Dna Mismatch ◽  
Dominant Component ◽  
Colon Cancers

: The microsatellite instable phenotype resulting from errors in DNA mismatch repair proteins accounts for as far as 15 to 20% of non-hereditary colon cancers but is scarce in rectal cancer. It has been shown that the increased existence of tumor-specific neoantigens in hypermutated tumors is correlated with higher tumor-infiltrating lymphocytes (TILs) and overexpression of immune checkpoint receptors and ligands, mainly PD-1 and PD-L1. In particular, the data gained up to now gives evidence that neoantigen recognition constitutes a dominant component in the course of immunotherapies. This review's primary objective is to describe current approvals and summarize present knowledge about the outcomes of immuno-oncology treatment of microsatellite instable colorectal cancer (CRC). The secondary objective is to give a narrative report about testing methodologies, prognostics, and the predictive value of microsatellite instability. For this purpose, a literature review was performed, focusing on published clinical trial results, ongoing clinical trials and timelines, testing methods, and prognostic and predictive value of MSI. Following four recent FDA approvals of immunotherapy of MSI-high CRC, further work should be warranted by pathology societies towards standardization and rising concordance and reproducibility across the IHC/MSI testing landscape in order to facilitate professionals to offer better survival options for patients with CRC.

Increased risk for abnormalities on perioperative colon screening in patients with microsatellite instability–positive endometrial carcinoma

2006 ◽  
Vol 16 (6) ◽  
pp. 1980-1986 ◽  
Author(s):  
B. M. Buttin ◽  
M. A. Powell ◽  
P. J. Goodfellow ◽  
S. N. Lewin ◽  
R. K. Gibb ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Microsatellite Instability ◽  
Medical Records ◽  
Fisher Exact Test ◽  
Exact Test ◽  
Molecular Stratification ◽  
Colon Cancers ◽  
Increased Risk ◽  
Primary Colon ◽  
Endometrial Cancers

Microsatellite instability (MSI) is a feature of certain hereditary and sporadic endometrial and colon cancers. We set out to determine whether molecular stratification of endometrial cancers based on tumor MSI status could help identify patients at increased risk for abnormalities found on perioperative colon screening. From a prospectively accrued series of 413 patients, medical records were reviewed from 94 patients with MSI positive (MSI+) and 94 patients with MSI negative (MSI−) endometrial cancers, matched by year of diagnosis. We reviewed clinicopathologic data and results of perioperative colon screening. Differences were analyzed using Fisher exact test and logistic regression analysis. There were no significant clinicopathologic differences between the two cohorts. Sixty-five percent of patients in each group underwent perioperative colon screening. However, patients with MSI+ cancers had a twofold increase in the frequency of colonic abnormalities (30% versus 14.8%, P= 0.044) over those with MSI− cancers. Furthermore, the only primary colon cancers (N= 2) were found in women with MSI+ endometrial cancers that were unmethylated at the MLH1 promoter. Our data suggest that patients with MSI+ endometrial cancers are at increased risk for abnormalities on perioperative colon screening. Those with MSI+MLH1 unmethylated cancers appear to be at highest risk.

Extensive but hemiallelic methylation of the hMLH1 promoter region in early-onset sporadic colon cancers with microsatellite instability

2004 ◽  
Vol 2 (2) ◽  
pp. 147-156 ◽  
Author(s):  
Yasuyuki Miyakura ◽  
Kokichi Sugano ◽  
Takayuki Akasu ◽  
Teruhiko Yoshida ◽  
Masato Maekawa ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Early Onset ◽  
Promoter Region ◽  
Colon Cancers

scholarly journals MUC Gene Abnormalities in Sporadic and Hereditary Mucinous Colon Cancers with Microsatellite Instability

2005 ◽  
Vol 21 (3) ◽  
pp. 121-126 ◽  
Author(s):  
Chiara Pastrello ◽  
Manuela Santarosa ◽  
Mara Fornasarig ◽  
Roberto Sigon ◽  
Tiziana Perin ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Southern Blotting ◽  
Repetitive Sequences ◽  
Variable Number ◽  
Molecular Pathway ◽  
Colon Cancers ◽  
Tandem Repetition ◽  
Indirect Consequence ◽  
Muc Genes ◽  
Gene Alterations

Aim of this study was verifying whether mucin producing colon cancers (CRCs) could develop through a molecular pathway involving microsatellite instability (MSI) and MUC gene alterations. Out of 49 CRCs expressing variable amounts of mucin, 22 (44.9%) were MSI-H and 5 (10.2%) were MSI-L. MUC genes were analyzed by Southern blotting and extra bands were evident in the Variable Number Tandem Repetition (VNTR) regions of MUC2 (5 cases) and MUC5AC (2 cases), but not MUC1 and MUC4 genes. Since the somatic VNTR abnormalities were detected in 6 MSI-H and in 1 MSI-L tumors, they seem to be peculiar of mismatch repair defective CRCs. Our finding suggests that alteration and/or loss of structurally normal MUC genes may be an important step in the neoplastic molecular pathway of a subset of CRCs and that mutations involving VNTR repetitive sequences may exist in MSI tumors as a direct and/or indirect consequence of an inefficient MMR system.

Regional Bias of Intratumoral Genetic Heterogeneity of Nucleotide Repeats in Colon Cancers with Microsatellite Instability

2014 ◽  
Vol 20 (4) ◽  
pp. 965-971 ◽  
Author(s):  
Youn Jin Choi ◽  
Min Sung Kim ◽  
Chang Hyeok An ◽  
Nam Jin Yoo ◽  
Sug Hyung Lee
Keyword(s):  
Microsatellite Instability ◽  
Genetic Heterogeneity ◽  
Regional Bias ◽  
Colon Cancers ◽  
Nucleotide Repeats

Epidermal growth factor receptor expression correlates with histologic grade but not microsatellite instability in primary colon carcinomas

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 20023-20023
Author(s):  
R. L. Rego ◽  
A. J. French ◽  
N. R. Foster ◽  
D. J. Sargent ◽  
S. R. Alberts ◽  
...  
Keyword(s):  
Overall Survival ◽  
Microsatellite Instability ◽  
Disease Free Survival ◽  
Receptor Expression ◽  
High Dose ◽  
Colon Cancers ◽  
Egfr Expression ◽  
Primary Colon ◽  
Weighted Score ◽  
Clinicopathological Variables

20023 Background: EGFR is a transmembrane receptor tyrosine kinase belonging to the ErbB family of proteins. Anti-EGFR antibodies have shown efficacy as monotherapy and can enhance cytotoxic chemotherapy in patients with advanced colorectal cancers. We studied EGFR expression in primary colon cancers and its association with, microsatellite instability (MSI), clinicopathological variables and patient survival rates. Methods: Archival colon carcinomas were studied from patients with high risk Dukes’ stage B2 (n = 78) and C (n = 230) patients enrolled in a prior adjuvant trial of 5-fluorouracil, leucovorin plus standard dose or high-dose levamisole (NCCTG 91–46–53). EGFR expression (anti-EGFR H11 antibody, DAKO) was analyzed by immunohistochemistry (IHC) and intensity (0–3+), extent and their product (weighted score) were determined. MSI was analyzed using BAT26 and expression of hMLH1, hMSH2 and hMSH6 proteins by IHC. Patients were censored at 5 years after randomization for DFS and censored at 8 years post study randomization for overall survival (OS) data. Results: EGFR protein expression was detected in 216 of 308 (70%) of Dukes’ B2 and C primary colon carcinomas from patients and localized to the plasma membrane. EGFR expression variables (intensity, extent, weighted score) were increased in poor/undifferentiated compared to moderate/well differentiated tumors (p ≤ 0.036). Similar EGFR expression levels were found in MSI-H (n = 27) versus MSS (n = 203) colon cancers and for other clinicopathological variables. EGFR intensity was more likely moderate (2+) or strong (3+) in Dukes’ C versus B2 tumors (p = 0.088). In addition, higher EGFR intensity (2+, 3+) showed a trend toward worse disease-free survival (5 yr DFS %: 62.2 vs. 71.7; p = 0.095), but not overall survival (p = 0.14). Conclusions: EGFR overexpression is associated with increased tumor aggressiveness as indicated by poor tumor cell differentiation and reduced DFS in colon cancer patients receiving adjuvant 5-FU and levamisole. These findings indicate that EGFR may be an important therapeutic target in the adjuvant setting. [Table: see text]

scholarly journals Alterations in cell proliferation and apoptosis in colon cancers with microsatellite instability

2007 ◽  
Vol 120 (6) ◽  
pp. 1232-1238 ◽  
Author(s):  
Frank A. Sinicrope ◽  
Rafaela L. Rego ◽  
Megan M. Garrity-Park ◽  
Nathan R. Foster ◽  
Daniel J. Sargent ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Microsatellite Instability ◽  
Colon Cancers ◽  
Proliferation And Apoptosis
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