Strambu V, Garofil D, Pop F, Radu P, Bratucu M, Popa F
Department of General Surgery, "Carol Davila" Clinical Nephrology Hospital, Bucharest, Romania.
Department of Pathology, "Carol Davila" Clinical Nephrology Hospital, Bucharest, Romania.
J Med Life. 2014 Mar 15;7(1):17-26. Epub 2014 Mar 25.
Although multimodal treatment has brought important benefit, there is still great heterogeneity regarding the indication and response to chemotherapy in Stage II and III, and individual variations related to both overall survival and toxicity of new therapies in metastatic disease or tumor relapse. Recent research in molecular biology led to the development of a large scale of genetic biomarkers, but their clinical use is not concordant with the high expectations. The Aim of this review is to identify and discuss the molecular markers with proven clinical applicability as prognostic and/or predictive factors in CRC and also to establish a feasible algorithm of molecular testing, as routine practice, in the personalized, multidisciplinary approach of colorectal cancer patients in our country. Despite the revolution that occurred in the field of molecular marker research, only Serum CEA, Immunohistochemical analysis of mismatch repair proteins and PCR testing for KRAS and BRAF mutations have confirmed their clinical utility in the management of colorectal cancer. Their implementation in the current practice should partially resolve some of the controversies related to this heterogenic pathology, in matters of prognosis in different TNM stages, stage II patient risk stratification, diagnosis of hereditary CRC and likelihood of benefit from anti EGFR therapy in metastatic disease. The proposed algorithms of molecular testing are very useful but still imperfect and require further validation and constant optimization.
尽管多模式治疗带来了重要益处,但在II期和III期患者中,化疗的适应症和反应仍存在很大异质性,并且在转移性疾病或肿瘤复发中,新疗法的总生存期和毒性存在个体差异。分子生物学的最新研究促使大量基因生物标志物得以开发,但其临床应用并未达到人们的高度期望。本综述的目的是识别和讨论在结直肠癌中已被证明具有临床适用性的分子标志物,作为预后和/或预测因素,并在我国结直肠癌患者的个性化多学科治疗中,建立一种可行的分子检测算法作为常规做法。尽管分子标志物研究领域发生了变革,但只有血清癌胚抗原、错配修复蛋白的免疫组化分析以及KRAS和BRAF突变的PCR检测已证实其在结直肠癌治疗中的临床效用。将它们应用于当前实践应能部分解决与这种异质性病理相关的一些争议,包括不同TNM分期的预后、II期患者风险分层、遗传性结直肠癌的诊断以及转移性疾病中抗表皮生长因子受体治疗的获益可能性。所提出的分子检测算法非常有用,但仍不完善,需要进一步验证和持续优化。