Influence of Immunoexpression of Mismatch Repair Complex Proteins on Disease-Free Survival in Non-Surgically Treated Oropharyngeal Squamous Cell Carcinomas

被引:0
作者
Coelho, Livia Moreira Caetano [1 ]
Dantas, Thinali Sousa [2 ,3 ]
Silva, Paulo Goberlanio de Barros [1 ,2 ,3 ,6 ]
Barbosa, Jennifer Vianna [3 ]
Teixeira, Andre Costa [2 ]
Alves, Ana Paula Negreiros Nunes [1 ]
Mota, Mario Rogerio Lima [1 ]
Vila, Pilar Gandara [4 ]
Ortega, Karem L. [4 ,5 ]
Sousa, Fabricio Bitu [1 ,2 ]
机构
[1] Univ Fed Ceara, Lab Oral Pathol, Fortaleza, Ceara, Brazil
[2] Unichristus, Dept Dent, Fortaleza, Ceara, Brazil
[3] Haroldo Juacaba Hosp, Ceara Canc Inst, Fortaleza, Ceara, Brazil
[4] Univ Santiago de Compostela, Fac Med & Dent, Santiago De Compostela, Spain
[5] Univ Sao Paulo, Dept Dent, Sao Paulo, Brazil
[6] Ctr Univ Christus Unichristus, Dent Course, 133 Joao Adolfo Gurgel St, BR-60190060 Fortaleza, Ceara, Brazil
关键词
Squamous cell carcinoma; Oropharynx; Immunohistochemistry; MutS proteins; MutL proteins; Survival analysis; HUMAN-PAPILLOMAVIRUS; ORAL-CAVITY; CANCER; HEAD; P16(INK4A); PROGNOSIS; DAMAGE; GENES; HMLH1; PMS2;
D O I
10.1007/s12105-024-01736-0
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
ObjectiveTo evaluate the influence of MMR complex protein immunoexpression on disease-free survival in oropharyngeal SCC treated non-surgically. Materials and methods: 85 cases of oropharyngeal SCC diagnosed and treated at the Cear & aacute; Cancer Institute were surveyed, from which clinical-pathological data and paraffin blocks of incisional biopsies were retrieved for immunohistochemical reaction for MSH2, MSH6, PMS2, MLH1 and p16. Disease-free survival was calculated and Kruskal-Wallis and Friedman/Dunn tests, chi-square and Fisher's exact, Log-Rank Mantel Cox and Cox regression were performed. Results: In p16- tumors, loss of MSH2 expression was associated with shorter disease-free survival (p = 0.035) and mean MSH6 expression was significantly higher than MSH2 (p = 0.001). Loss of MSH2 expression in p16 + tumors was associated with longer disease-free survival compared to p16- tumors. Imbalance in the MSH6/MSH2 ratio in p16 + tumors was associated with longer survival compared to p16- tumors. MLH1/PMS2 imbalance was significantly higher in p16 + with recurrence (p = 0.003). Low MSH2 immunoexpression increased the risk of relapse by 9.10 times (CI95% 1.99 to 83.06). Conclusion: Microsatellite instability in oropharyngeal SCC is demonstrated by the association between loss of protein expression and its heterodimer imbalance with disease-free survival. It was demonstrated that the imbalance of the MMR complex can consequently lead to resistance to treatment and a decrease in disease-free survival in p16 + oropharyngeal SCC tumors.
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页数:15
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共 40 条
[1]   Response to Chemotherapy and Prognosis in Metastatic Colorectal Cancer With DNA Deficient Mismatch Repair [J].
Alex, Alexandra Khichfy ;
Siqueira, Sheila ;
Coudry, Renata ;
Santos, Juliana ;
Alves, Michel ;
Hoff, Paulo M. ;
Riechelmann, Rachel P. .
CLINICAL COLORECTAL CANCER, 2017, 16 (03) :228-239
[2]   Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer [J].
Ang, K. Kian ;
Harris, Jonathan ;
Wheeler, Richard ;
Weber, Randal ;
Rosenthal, David I. ;
Nguyen-Tan, Phuc Felix ;
Westra, William H. ;
Chung, Christine H. ;
Jordan, Richard C. ;
Lu, Charles ;
Kim, Harold ;
Axelrod, Rita ;
Silverman, C. Craig ;
Redmond, Kevin P. ;
Gillison, Maura L. .
NEW ENGLAND JOURNAL OF MEDICINE, 2010, 363 (01) :24-35
[3]  
[Anonymous], 2018, Revista Brasileira de Cancerologia, V64, P119, DOI DOI 10.32635/2176-9745.RBC.2018V64N1.115
[4]   Oropharyngeal squamous cell carcinoma: p16/p53 immunohistochemistry as a strong predictor of HPV tumour status [J].
Benzerdjeb, Nazim ;
Tantot, Juliet ;
Blanchet, Christophe ;
Philouze, Pierre ;
Mekki, Yahia ;
Lopez, Jonathan ;
Devouassoux-Shisheboran, Mojgan .
HISTOPATHOLOGY, 2021, 79 (03) :381-390
[5]   Changes in treatment of advanced oropharyngeal cancer, 1985-2001 [J].
Chen, Amy Y. ;
Schrag, Nicole ;
Hao, Yongping ;
Stewart, Andrew ;
Ward, Elizabeth .
LARYNGOSCOPE, 2007, 117 (01) :16-21
[6]   Pathological Features and Prognostication in Colorectal Cancer [J].
Chen, Kabytto ;
Collins, Geoffrey ;
Wang, Henry ;
Toh, James Wei Tatt .
CURRENT ONCOLOGY, 2021, 28 (06) :5356-5383
[7]   Oral cavity and oropharyngeal squamous cell carcinomaan update [J].
Chi, Angela C. ;
Day, Terry A. ;
Neville, Brad W. .
CA-A CANCER JOURNAL FOR CLINICIANS, 2015, 65 (05) :401-421
[8]   Mechanisms of human DNA repair: an update [J].
Christmann, M ;
Tomicic, MT ;
Roos, WP ;
Kaina, B .
TOXICOLOGY, 2003, 193 (1-2) :3-34
[9]   The Mismatch Repair System (MMR) in Head and Neck Carcinogenesis and Its Role in Modulating the Response to Immunotherapy: A Critical Review [J].
Cilona, Maria ;
Locatello, Luca Giovanni ;
Novelli, Luca ;
Gallo, Oreste .
CANCERS, 2020, 12 (10) :1-21
[10]   HPV induction of APOBEC3 enzymes mediate overall survival and response to cisplatin in head and neck cancer [J].
Conner, Kayla L. ;
Shaik, Asra N. ;
Ekinci, Elmira ;
Kim, Seongho ;
Ruterbusch, Julie J. ;
Cote, Michele L. ;
Patrick, Steve M. .
DNA REPAIR, 2020, 87