scholarly journals The Mismatch Repair System (MMR) in Head and Neck Carcinogenesis and Its Role in Modulating the Response to Immunotherapy: A Critical Review

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3006
Author(s):  
Maria Cilona ◽  
Luca Giovanni Locatello ◽  
Luca Novelli ◽  
Oreste Gallo
Keyword(s):  
Microsatellite Instability ◽  
Head And Neck ◽  
Mismatch Repair ◽  
Checkpoint Inhibitors ◽  
Precancerous Lesions ◽  
Second Primary ◽  
Repair System ◽  
Primary Tumors ◽  
Wide Range

The mismatch repair (MMR) system has a major role in the detection and correction of DNA replication errors, resulting from DNA polymerase slippage or nucleotides misincorporation. Specific inherited/acquired alterations or epigenetic inactivation of MMR genes are associated with microsatellite instability (MSI): the loss of crucial function in repairing DNA alterations can promote carcinogenesis by favoring the accumulation of thousands of mutations in a broad spectrum of different anatomic sites such as colon, stomach, prostate, esophagus, endometrium, lung and head and neck. Recent extensive data suggest that tumor mutational burden strongly correlates with a clinical response to immunotherapy using checkpoint inhibitors and this response is influenced by MMR deficiency in a wide range of human solid cancers. In this context, few data about this crucial point are available for head and neck cancer (HNC). In this review, we discuss the role of MMR alterations and the resulting MSI in HNC pathogenesis. Furthermore, by summarizing the clinical available data on how they influence the progression of precancerous lesions and the risk of recurrence or second primary tumors, we want to define the current role of MSI in the management of HNC. Finally, we analyze the complex interaction between cancer cells and the immune system addressing the data now available about a potential correlation between microsatellite instability and immunotherapy response in HNC.

scholarly journals Microsatellite instability as a unique characteristic of tumors and a predictor of response to immune therapy

2020 ◽  
Vol 9 (4) ◽  
pp. 59-69 ◽  
Author(s):  
A.  A. Tryakin ◽  
M.  Yu. Fedyanin ◽  
A.  S. Tsukanov ◽  
Yu.  A. Shelygin ◽  
I.  A. Pokataev ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Immune Therapy ◽  
High Sensitivity ◽  
Repair System ◽  
Favorable Prognosis ◽  
Mismatch Repair System ◽  
High Immunogenicity

Deficiency of the mismatch repair system is a unique molecular disorder that occurs in most types of tumors and leads to development of microsatellite instability (MSI) in them. The development of a hypermutated phenotype and related high immunogenicity are typically associated with more favorable prognosis as well as a high sensitivity to immunotherapy with inhibitors of immune checkpoint inhibitors. This review presents the current views on the diagnosis, prognostic and predictive significance of MSI in various tumors, as well as their response to immunotherapy.

Clinicopathologic and Pedigree Differences in Amsterdam I–Positive Hereditary Nonpolyposis Colorectal Cancer Families According to Tumor Microsatellite Instability Status

2007 ◽  
Vol 25 (7) ◽  
pp. 781-786 ◽  
Author(s):  
Laura Valle ◽  
Jose Perea ◽  
Pablo Carbonell ◽  
Victoria Fernandez ◽  
Ana M. Dotor ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Repair System ◽  
Primary Tumors ◽  
Multiple Primary Tumors ◽  
Hereditary Nonpolyposis ◽  
Multiple Primary

Purpose To establish the clinicopathologic and familial differences within Amsterdam I–positive families, showing either tumor microsatellite instability (MSI) or microsatellite stability (MSS) in order to confirm or deny the existence of hereditary nonpolyposis colorectal cancer (HNPCC) without defects in the mismatch repair system. Patients and Methods Sixty-four Amsterdam I–positive families were included in the study for which full, three-generation, family medical histories and colorectal paraffin-embedded tumors were obtained. Both personal and clinicopathologic information of patients were collected. In all cases, both the MSI status and the mismatch repair (MMR) protein expression were analyzed. MMR genetic testing was performed on the MSI families. Results Of the Amsterdam I–positive families, 59.4% were tumor MSI, and 40.6% were tumor MSS. When comparing both groups, the statistical differences were observed in the age of onset (MSI, 41 years; MSS, 53 years); in the colorectal tumor location, more frequently proximal in MSI cases; in fewer mucinous tumors in MSS; and loss of MMR protein expression in the MSI tumors. Regarding the individual and familial cancer history, we observed a predominance of individuals with multiple primary tumors in MSI pedigrees, as well as differences in the type of tumors developed within the family. Conclusion Our findings support the suspicion of another hereditary colorectal syndrome different from HNPCC and characterized by MSS, the normal MMR immunohistochemical expression, the presence of only colorectal tumors, and the absence of individuals with multiple primary tumors. All these circumstances suggest the existence of a non-MMR gene being responsible for this new syndrome.

scholarly journals Beyond Microsatellite Instability: Evolving Strategies Integrating Immunotherapy for Microsatellite Stable Colorectal Cancer

2021 ◽  
Vol 22 (8) ◽  
Author(s):  
Federica Pecci ◽  
Luca Cantini ◽  
Alessandro Bittoni ◽  
Edoardo Lenci ◽  
Alessio Lupi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Cancer Progression ◽  
Checkpoint Inhibitors ◽  
Tnm Classification ◽  
Standard Of Care ◽  
First Line Therapy ◽  
Combination Strategies ◽  
The Impact

Opinion statementAdvanced colorectal cancer (CRC) is a heterogeneous disease, characterized by several subtypes with distinctive genetic and epigenetic patterns. During the last years, immune checkpoint inhibitors (ICIs) have revamped the standard of care of several tumors such as non-small cell lung cancer and melanoma, highlighting the role of immune cells in tumor microenvironment (TME) and their impact on cancer progression and treatment efficacy. An “immunoscore,” based on the percentage of two lymphocyte populations both at tumor core and invasive margin, has been shown to improve prediction of treatment outcome when added to UICC-TNM classification. To date, pembrolizumab, an anti-programmed death protein 1 (PD1) inhibitor, has gained approval as first-line therapy for mismatch-repair-deficient (dMMR) and microsatellite instability-high (MSI-H) advanced CRC. On the other hand, no reports of efficacy have been presented in mismatch-repair-proficient (pMMR) and microsatellite instability-low (MSI-L) or microsatellite stable (MSS) CRC. This group includes roughly 95% of all advanced CRC, and standard chemotherapy, in addition to anti-EGFR or anti-angiogenesis drugs, still represents first treatment choice. Hopefully, deeper understanding of CRC immune landscape and of the impact of specific genetic and epigenetic alterations on tumor immunogenicity might lead to the development of new drug combination strategies to overcome ICIs resistance in pMMR CRC, thus paving the way for immunotherapy even in this subgroup.

scholarly journals Early detection of esophageal second primary tumors using Lugol chromoendoscopy in patients with head and neck cancer: A systematic review and meta‐analysis

Head & Neck ◽  
2018 ◽  
Vol 41 (4) ◽  
pp. 1122-1130 ◽  
Author(s):  
Oisín Bugter ◽  
Steffi E. M. van de Ven ◽  
Jose A. Hardillo ◽  
Marco J. Bruno ◽  
Arjun D. Koch ◽  
...  
Keyword(s):  
Systematic Review ◽  
Head And Neck Cancer ◽  
Early Detection ◽  
Head And Neck ◽  
Neck Cancer ◽  
Meta Analysis ◽  
Second Primary ◽  
Primary Tumors ◽  
Second Primary Tumors

The role of molecular biology in the diff erential diagnosis of pancreatic cystic neoplasias

2021 ◽  
Vol 75 (5) ◽  
pp. 417-423
Author(s):  
Ivo Horný ◽  
Tomáš Hucl
Keyword(s):  
Precancerous Lesions ◽  
Clinical Status ◽  
Pancreatic Disease ◽  
Pancreatic Cysts ◽  
Cytological Examination ◽  
Asymptomatic Patients ◽  
Wide Range ◽  
Risk Of Malignancy ◽  
History Of

Summary: Pancreatic cysts have been detected ever more frequently in recent years due to the advanced and wider use of imaging methods. We find them on CT or MR also in asymptomatic patients who do not have a history of any pancreatic disease. Pancreatic cystic lesions represent a wide range of pathological changes from simple cysts through precancerous lesions to malignant cysts. Accurate dia­gnosis remains difficult despite the combination of clinical status evaluation, imaging findings, and bio­chemical and cytological examination. Molecular bio­logical examination of cyst aspirate obtained by endosonographic examination increases the detection rate of mucinous cysts (KRAS/GNAS/VHL) and cysts with a high risk of malignancy (KRAS/GNAS/p53/PIK3CA/PTEN/CDKN2A/SMAD4) and optimizes therapeutic approach. Larger prospective validation studies are necessary to make this costly and limited method a routine part of clinical practice. Key words: molecular bio­logy – neoplasia – pancreatic cysts

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