Taillade L, Penault-Llorca F, Boulet T, Fouret P, Michiels S, Taranchon E, Mountzios G, Validire P, Domont J, Girard P, Grunenwald D, Le Chevalier T, Soria J-C
Department of Medicine, Institut Gustave Roussy, Villejuif, France.
Ann Oncol. 2007 Jun;18(6):1043-50. doi: 10.1093/annonc/mdm072. Epub 2007 Mar 12.
The increasing use of biomarkers as molecular determinants of responsiveness to conventional chemotherapy or molecular targeted therapy has raised the question of the reliability and reproducibility of their evaluation in bronchial biopsies as compared with corresponding resected surgical specimens.
Immunohistochemical expression of five markers related to signal transduction [epidermal growth factor receptor (EGFR), phospho-Akt], cell proliferation (Ki-67), DNA repair [excision repair cross-complementing (ERCC)1] and cellular 'immortality' [human telomerase catalytic component (hTERT)], was assessed in 41 patients with operable non-small-cell lung cancer in both bronchial biopsies and whole surgical specimens.
High correlation coefficients were observed between the expression of ERCC1, hTERT and Ki-67 in the biopsies and the surgical specimens [0.83 (P < 0.0001); 0.55 (P < 0.001) and 0.64 (P < 0.0001), respectively]. On the other hand, biomarker expression in biopsy was less correlated with the expression in the whole tissue sample for the markers of signal response and transduction [0.24 (P = 0.17) and 0.29 (P = 0.09) for EGFR and phospho-Akt, respectively].
Our results indicate a lack of association in the expression of important biomarkers between lung biopsies and corresponding resected tumors, with discordance rates ranging between 9% and 41%. Although these results need to be further validated in larger cohorts, they indicate that the evaluation of the expression of biomarkers in bronchial biopsies can be misleading.
生物标志物作为传统化疗或分子靶向治疗反应性的分子决定因素，其在支气管活检中的评估与相应手术切除标本相比的可靠性和可重复性问题日益受到关注。
对41例可手术切除的非小细胞肺癌患者的支气管活检标本和完整手术标本，评估了与信号转导相关的5种标志物[表皮生长因子受体（EGFR）、磷酸化Akt]、细胞增殖（Ki-67）、DNA修复[切除修复交叉互补蛋白（ERCC）1]和细胞“永生性”[人端粒酶催化亚基（hTERT）]的免疫组化表达。
活检标本和手术标本中ERCC1、hTERT和Ki-67的表达之间观察到高相关系数[分别为0.83（P<0.0001）；0.55（P<0.001）和0.64（P<0.0001）]。另一方面，对于信号反应和转导标志物，活检中的生物标志物表达与整个组织样本中的表达相关性较低[EGFR和磷酸化Akt分别为0.24（P = 0.17）和0.29（P = 0.09）]。
我们的结果表明，肺活检与相应切除肿瘤之间重要生物标志物的表达缺乏相关性，不一致率在9%至41%之间。尽管这些结果需要在更大的队列中进一步验证，但它们表明支气管活检中生物标志物表达的评估可能会产生误导。
