Is tumor testing efficiency for Lynch syndrome different in rectal and colon cancer?. Marabelli, M.; Gandini, S.; Rafaniello, P. R.; Calvello, M.; Tolva, G.; Feroce, I.; Lazzeroni, M.; Marino, E.; Dal Molin, M.; Trovato, C.; Guerrieri-Gonzaga, A.; Petz, W. L.; Barberis, M.; Bertario, L.; and Bonanni, B. Digestive and Liver Disease: Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, June, 2020.
doi  abstract   bibtex   
BACKGROUND: Tumor testing utility in Lynch syndrome (LS) diagnosis is established. AIMS: Analyze the differences between tumor testing efficiency in rectal (RC) and colon cancer (CC). METHODS: We performed immunohistochemistry (IHC) for MisMatch Repair (MMR) proteins (IHC-MMR) and MicroSatellite Instability analysis (MSI) on 482 unselected primary tumors: 320 CCs and 162 RCs. Samples had proficient-IHC, deficient-IHC or borderline-IHC ("patchy" expression). MSI-H borderline-IHC tumors were considered as likely MMR-deficient. Germline testing was offered to MMR-deficient patients without BRAF mutation or MLH1 promoter hypermetilation (MLH1-Hy). RESULTS: We identified 51/482 (10.6%) MMR-defective tumors. Multivariable analysis demonstrated a significant correlation between tumor testing results with histotype, lymph-node involvement and tumor location. In particular, RC showed a lower MMR-deficiency rate than CC (p\textless0.0001). Interestingly, MLH1 loss was detected in 0% RCs and 76.1% CCs, with 80% of them showing BRAF mutation/MLH1-Hy. A germline variant was detected in 12 out of 18 patients (mutation detection rate of 66.7%). CONCLUSION: Tumor testing results showed molecular differences between CCs and RCs, in terms of MMR proteins expression, and presence of BRAF mutation/MLH1-Hy. MSH6 variants were the most frequent ones (50%). Although young age at diagnosis was associated with mutation detection (p = 0.045), 33.3% of LS patients were \textgreater50 years.
@article{marabelli_is_2020,
	title = {Is tumor testing efficiency for {Lynch} syndrome different in rectal and colon cancer?},
	issn = {1878-3562},
	doi = {10.1016/j.dld.2020.06.002},
	abstract = {BACKGROUND: Tumor testing utility in Lynch syndrome (LS) diagnosis is established.
AIMS: Analyze the differences between tumor testing efficiency in rectal (RC) and colon cancer (CC).
METHODS: We performed immunohistochemistry (IHC) for MisMatch Repair (MMR) proteins (IHC-MMR) and MicroSatellite Instability analysis (MSI) on 482 unselected primary tumors: 320 CCs and 162 RCs. Samples had proficient-IHC, deficient-IHC or borderline-IHC ("patchy" expression). MSI-H borderline-IHC tumors were considered as likely MMR-deficient. Germline testing was offered to MMR-deficient patients without BRAF mutation or MLH1 promoter hypermetilation (MLH1-Hy).
RESULTS: We identified 51/482 (10.6\%) MMR-defective tumors. Multivariable analysis demonstrated a significant correlation between tumor testing results with histotype, lymph-node involvement and tumor location. In particular, RC showed a lower MMR-deficiency rate than CC (p{\textless}0.0001). Interestingly, MLH1 loss was detected in 0\% RCs and 76.1\% CCs, with 80\% of them showing BRAF mutation/MLH1-Hy. A germline variant was detected in 12 out of 18 patients (mutation detection rate of 66.7\%).
CONCLUSION: Tumor testing results showed molecular differences between CCs and RCs, in terms of MMR proteins expression, and presence of BRAF mutation/MLH1-Hy. MSH6 variants were the most frequent ones (50\%). Although young age at diagnosis was associated with mutation detection (p = 0.045), 33.3\% of LS patients were {\textgreater}50 years.},
	language = {eng},
	journal = {Digestive and Liver Disease: Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver},
	author = {Marabelli, Monica and Gandini, Sara and Rafaniello, Paola Raviele and Calvello, Mariarosaria and Tolva, Gianluca and Feroce, Irene and Lazzeroni, Matteo and Marino, Elena and Dal Molin, Matteo and Trovato, Cristina and Guerrieri-Gonzaga, Aliana and Petz, Wanda Luisa and Barberis, Massimo and Bertario, Lucio and Bonanni, Bernardo},
	month = jun,
	year = {2020},
	pmid = {32620519},
	keywords = {Immunohistochemistry (IHC) for MisMatch Repair (MMR) proteins, Lynch syndrome, MicroSatellite Instability analysis (MSI), Tumor testing},
}
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