scholarly journals The Frequency of DNA Mismatch Repair Deficiency Is Very Low in Surgically Resected Lung Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Naoki Yanagawa ◽  
Noriyuki Yamada ◽  
Ryo Sugimoto ◽  
Mitsumasa Osakabe ◽  
Noriyuki Uesugi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Protein Expression ◽  
Microsatellite Instability ◽  
Cell Carcinoma ◽  
Mismatch Repair ◽  
Squamous Cell ◽  
Lung Carcinoma ◽  
The Other ◽  
Dna Mismatch ◽  
Mmr Deficiency

IntroductionDNA mismatch repair (MMR) deficiency leads to changes in the length of nucleotide repeat sequences of tumor DNA. In that situation, DNA replicational errors occur and accumulate during DNA replication. As a result, this mechanism frequently affects the coding regions of oncogenes and tumor suppressor genes and causes carcinogenesis. Recently, DNA MMR deficiency has been recognized as a predictive biomarker for immunotherapy. The aim of this study is to examine the frequency of DNA MMR deficiency and clinicopathological characteristics in surgically resected lung carcinoma (LC) and their correlation.MethodsA total of 1153 LCs were examined. Tissue microarrays were constructed. The status of MMR deficiency was evaluated by immunohistochemical analysis of MMR protein expression (hMLH1, hMSH2, hMSH6, and hPMS2). Microsatellite instability analysis, BRAF mutation, and MLH1 methylation analysis were performed for cases that showed MMR deficiency.ResultsOnly 2 of the 1153 cases (0.17%) showed a loss of hMLH1/hPMS2 protein expression. They also had high levels of microsatellite instability (MSI-H), had neither MLH1 promoter methylation nor BRAF mutation, and were male smokers. Histopathologically, one was a squamous cell carcinoma, and the other was combined small cell carcinoma with squamous cell carcinoma. Regarding PD-L1 protein expression, one had high expression, and the other had none.ConclusionThe frequency of MMR deficiency was very low in LC. However, our two cases were non-adenocarcinoma and differed from previous studies. Because of its very low frequency, MMR deficiency is not a practical biomarker to predict the effect of immune checkpoint inhibitors in LC.

scholarly journals No Evidence of Microsatellite Instability and Loss of Mismatch-Repair-Protein Expression in Squamous Cell Carcinoma of the Penis

Pathobiology ◽  
2019 ◽  
Vol 86 (2-3) ◽  
pp. 145-151 ◽  
Author(s):  
Robert Stoehr ◽  
Olaf Wendler ◽  
Johannes Giedl ◽  
Nadine T. Gaisa ◽  
Georg Richter ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Protein Expression ◽  
Microsatellite Instability ◽  
Cell Carcinoma ◽  
Mismatch Repair ◽  
Squamous Cell ◽  
Repair Protein ◽  
Mismatch Repair Protein

scholarly journals Mismatch Repair Protein Expression and Microsatellite Instability in Cutaneous Squamous Cell Carcinoma

2021 ◽  
Vol 28 (5) ◽  
pp. 3316-3322
Author(s):  
Thilo Gambichler ◽  
Nomun Ganjuur ◽  
Andrea Tannapfel ◽  
Markus Vogt ◽  
Lisa Scholl ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Protein Expression ◽  
Microsatellite Instability ◽  
Cell Carcinoma ◽  
Mismatch Repair ◽  
Squamous Cell ◽  
Expression Profiles ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Small Subset ◽  
Low Level

There exist relatively sparse and conflicting data on high-level microsatellite instability (MSI-H) and deficient mismatch repair (dMMR) in cutaneous malignancies. We aimed to determine the expression profiles of MMR proteins (MSH2, MSH6, MLH1, and PMS2) in different progression stages of cutaneous squamous cell carcinoma (cSCC, 102 patients in total) by immunohistochemistry, and search for MSI-H in patients with low-level MMR or dMMR using multiplex-PCR. Low-level MMR protein expression was observed in five patients: One patient with primary cSCC < 2 mm thickness and low-level MLH1, three patients with primary cSCC > 6 mm (including one with low-level MSH2, as well as MSH6 expression, and two with low-level PMS2), and one patient with a cSCC metastasis showing low-level MSH2 as well as MSH6. Intergroup protein expression analysis revealed that MLH1 and MSH2 expression in actinic keratosis was significantly decreased when compared to Bowen’s disease, cSCC < 2 mm, cSCC > 6 mm, and cSCC metastasis. In cases with low-level MMR, we performed MSI-H tests revealing three cases with MSI-H and one with low-level MSI-L. We found low-level MMR expression in a small subset of patients with invasive or metastatic cSCC. Hence, loss of MMR expression may be associated with tumour progression in a small subgroup of patients with non-melanoma skin cancer.

Reduced human mismatch repair protein expression in the development of precancerous skin lesions to squamous cell carcinoma

2001 ◽  
Vol 439 (5) ◽  
pp. 622-627 ◽  
Author(s):  
Sheng-Ben Liang ◽  
Mutsuo Furihata ◽  
Tamotsu Takeuchi ◽  
Hiroshi Sonobe ◽  
Yuji Ohtsuki
Keyword(s):  
Squamous Cell Carcinoma ◽  
Protein Expression ◽  
Cell Carcinoma ◽  
Mismatch Repair ◽  
Squamous Cell ◽  
Skin Lesions ◽  
Repair Protein ◽  
Mismatch Repair Protein

Decreased Fragile Histidine Triad Gene Protein Expression Is Associated With Worse Prognosis in Oral Squamous Carcinoma

2006 ◽  
Vol 130 (2) ◽  
pp. 158-164
Author(s):  
Leana A. Guerin ◽  
Henry T. Hoffman ◽  
M. Bridget Zimmerman ◽  
Robert A. Robinson
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cavity ◽  
Protein Expression ◽  
Microsatellite Instability ◽  
Cell Carcinoma ◽  
Loss Of Heterozygosity ◽  
Squamous Cell ◽  
Fhit Gene ◽  
Fragile Histidine Triad ◽  
Fhit Protein

Abstract Context.—Fragile histidine triad (FHIT) gene is thought to be a tumor suppressor; abnormalities in expression have been reported in a variety of neoplasms. Objective.—To determine whether abnormalities of FHIT protein expression or loss of heterozygosity in the FHIT gene were correlated with survival or other clinical parameters in patients with oral cavity squamous cell carcinoma. Design.—Fifty-three patients with initial surgical treatment of oral cavity squamous cell carcinoma were followed a minimum of 5 years or until death. The FHIT protein expression was studied by immunohistochemistry in all patients, and a subset of 20 patients was studied for allelic loss of heterozygosity and microsatellite instability using formalin-fixed, paraffin-embedded tissue. Results.—Sixty-one percent of patients whose tumors had reduced FHIT expression were dead of disease, and 37% of patients whose tumors exhibited preserved FHIT expression were dead of disease at 5-year follow-up. Log-rank analysis showed that patients retaining FHIT expression had a longer overall survival (P = .03) and disease-free survival (P = .01). The FHIT expression was not correlated with node status or clinical stage. Loss of heterozygosity was seen in 10 (50%) of 20 tumors, low levels of microsatellite instability in 4 (20%) of 20 tumors, and high levels of microsatellite instability in 1 (5%) of 20 tumors tested. Conclusions.—The FHIT gene was associated with a worse survival outcome when its expression was reduced in patients with oral cavity squamous cell carcinoma. Loss of heterozygosity in the gene was common, but no correlation with protein expression was found. Neither loss of heterozygosity nor microsatellite instability was found to correlate with survival. Because genomic alterations involving loss of heterozygosity of the FHIT gene were not associated with protein expression in these tumors, the presence or absence of FHIT expression may be controlled by other factors.

Association between genetic polymorphisms in DNA mismatch repair-related genes with risk and prognosis of head and neck squamous cell carcinoma

2015 ◽  
Vol 137 (4) ◽  
pp. 810-818 ◽  
Author(s):  
Guilherme Augusto Silva Nogueira ◽  
Gustavo Jacob Lourenço ◽  
Camila Borges Martins Oliveira ◽  
Fernando Augusto Lima Marson ◽  
Leisa Lopes-Aguiar ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Mismatch Repair ◽  
Genetic Polymorphisms ◽  
Squamous Cell ◽  
Dna Mismatch Repair ◽  
Neck Squamous Cell Carcinoma ◽  
Dna Mismatch
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