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错配修复复合物蛋白免疫表达对未经手术治疗的口咽鳞状细胞癌无病生存的影响。

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

机构信息

Laboratory of Oral Pathology, Federal University of Ceará, Fortaleza, Ceará, Brazil.

Department of Dentistry, Unichristus, Fortaleza, Ceará, Brazil.

出版信息

Head Neck Pathol. 2024 Nov 27;18(1):125. doi: 10.1007/s12105-024-01736-0.

Abstract

OBJECTIVE

To 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 Ceará 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.

摘要

目的

评估 MMR 复合蛋白免疫表达对非手术治疗的口咽 SCC 无病生存的影响。

材料与方法

对 Ceará 癌症研究所诊断和治疗的 85 例口咽 SCC 病例进行了调查,从中检索了临床病理数据和切取活检的石蜡块,进行 MSH2、MSH6、PMS2、MLH1 和 p16 的免疫组织化学反应。计算无病生存率,并进行了 Kruskal-Wallis 和 Friedman/Dunn 检验、卡方和 Fisher 确切检验、Log-Rank Mantel Cox 和 Cox 回归。

结果

在 p16-肿瘤中,MSH2 表达缺失与无病生存时间较短相关(p=0.035),且 MSH6 表达的平均值明显高于 MSH2(p=0.001)。p16+肿瘤中 MSH2 表达缺失与无病生存时间较长相关,而 p16-肿瘤则相反。p16+肿瘤中 MSH6/MSH2 比值失衡与无病生存时间较长相关,而 p16-肿瘤则相反。p16+伴复发肿瘤中 MLH1/PMS2 失衡明显更高(p=0.003)。低 MSH2 免疫表达使复发风险增加 9.10 倍(95%CI95% 1.99 至 83.06)。

结论

口咽 SCC 中微卫星不稳定性通过蛋白表达缺失及其异二聚体与无病生存之间的不平衡来证明。结果表明,MMR 复合物的失衡可能导致 p16+口咽 SCC 肿瘤对治疗的耐药性和无病生存率降低。

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