Department of Oncology, Rigshospitalet, 9 Blegdamsvej, 2100, Copenhagen, Denmark,
Cancer Chemother Pharmacol. 2014 Jan;73(1):43-51. doi: 10.1007/s00280-013-2315-6. Epub 2013 Nov 13.
Class-III-beta-tubulin (TUBB3) expression may be a potential predictive factor for treatment with microtubule interfering cytotoxic drugs in non-small cell lung cancer (NSCLC). Potential changes in TUBB3 expression during chemotherapy may be of interest if future choice of chemotherapy is to be based on TUBB3 expression. If the biomarker expression changes during chemotherapy, biopsies before initiation of chemotherapy beyond first line may be needed if treatment decision is to be based on TUBB3 expression. Thus, the aim was to explore TUBB3 expression heterogeneity and changes during chemotherapy.
TUBB3 expression was investigated by immunohistochemistry performed on diagnostic biopsies and on available subsequent resection specimens in 65 NSCLC patients stage T1-3N0-2 who received neoadjuvant carboplatin and paclitaxel (NAC-group). Another group of 53 NSCLC patients stage T1-4N0-1 was treated with surgery alone without preceding chemotherapy (OP-group). Paired repeated samples were compared in order to evaluate for changes in TUBB3 expression.
No statistically significant change in TUBB3 expression was observed between initial diagnostic biopsies and subsequent surgical resections of primary tumors in either the OP-group (p = 0.124) or the NAC-group (p = 0.414). When dichotomized into high and low TUBB3 expression, discordance between diagnostic biopsies and resection specimens of the primary tumors occurred in 22 % and 40 % in the OP-group and NAC-group, respectively (p = 0.169). Significantly more patients having low TUBB3 expression experienced down-staging during neoadjuvant chemotherapy compared to patients having high TUBB3 expression (p = 0.022).
A high degree of discordance of TUBB3 expression between paired repeated tumor samples was observed, which likely reflects intratumoral heterogeneity. This emphasizes a need for optimal tumor tissue samples in order to stratify patients based on TUBB3 expression. No significant changes in TUBB3 expression after neoadjuvant carboplatin and paclitaxel chemotherapy occurred, suggesting no need for rebiopsy in case second-line chemotherapy with microtubule interfering cytotoxic treatments is necessary.
III 类β-微管蛋白（TUBB3）的表达可能是预测非小细胞肺癌（NSCLC）患者接受微管干扰细胞毒性药物治疗的潜在因素。如果未来的化疗选择要基于 TUBB3 表达，那么化疗过程中 TUBB3 表达的潜在变化可能会引起关注。如果化疗过程中生物标志物表达发生变化，如果要基于 TUBB3 表达做出治疗决策，则需要在一线治疗前进行化疗前诊断性活检。因此，本研究旨在探讨 TUBB3 表达的异质性及其在化疗过程中的变化。
对 65 名接受新辅助卡铂和紫杉醇（NAC 组）治疗的 T1-3N0-2 期 NSCLC 患者的诊断性活检和可获得的后续切除标本进行 TUBB3 表达的免疫组织化学检测。另一组 53 名 T1-4N0-1 期 NSCLC 患者接受单纯手术治疗，无术前化疗（OP 组）。比较配对的重复样本，以评估 TUBB3 表达的变化。
OP 组（p=0.124）或 NAC 组（p=0.414）中，初始诊断性活检与原发性肿瘤后续手术切除之间的 TUBB3 表达均无统计学显著变化。当将 TUBB3 表达分为高表达和低表达时，OP 组和 NAC 组中诊断性活检和原发性肿瘤切除标本之间的不一致性分别为 22%和 40%（p=0.169）。与高 TUBB3 表达的患者相比，低 TUBB3 表达的患者在新辅助化疗期间经历降期的比例更高（p=0.022）。
观察到配对重复肿瘤样本之间 TUBB3 表达存在高度不一致，这可能反映了肿瘤内异质性。这强调了需要优化肿瘤组织样本，以便根据 TUBB3 表达对患者进行分层。新辅助卡铂和紫杉醇化疗后 TUBB3 表达无显著变化，提示如果需要二线微管干扰细胞毒性治疗的化疗，无需再次活检。
