Checinska Agnieszka, Oudejans Joost J, Span Simone W, Rodriguez Jose A, Kruyt Frank A E, Giaccone Giuseppe
Departments of Medical Oncology , VU University Medical Center, 1081 HV Amsterdam, The Netherlands.
Anticancer Res. 2006 Sep-Oct;26(5B):3819-24.
TUCAN is a caspase recruitment domain (CARD)-containing protein involved in tumor biology by regulating apoptosis and the NFkappaB pathway. Inhibition of caspase-9 may cause drug resistance. The pattern of expression, localization and prognostic value of TUCAN in the tumors of patients with non-small cell lung cancer (NSCLC) treated with chemotherapy were assessed in this study.
Using immunohistochemistry, the expression and localization of TUCAN was evaluated in forty-nine tumor specimens from patients with NSCLC who underwent neoadjuvant chemotherapy (32 stage IIB or IIIA), or palliative chemotherapy (17 stage IIIB or IV). The correlation between TUCAN expression and subcellular localization, major patient characteristics, response to the treatment and overall survival were assessed.
TUCAN expression was detectable in 34 out of 49 (69%) tumor specimens. Among the positively-stained specimens, three patterns of localization were observed: 5 samples (11%) showed exclusive nuclear localization, 13 samples (27%) contained only cytoplasmic staining and 15 (31%) showed both cytoplasmic and nuclear localization. There was no significant correlation between the localization of TUCAN and response to chemotherapy. Although TUCAN expression was not correlated with outcome, interestingly, exclusive cytoplasmic localization of TUCAN predicted shorter survival (p = 0.027).
Our results suggest that differential localization of TUCAN may be a prognostic factor for NSCLC, despite the lack of predictive value for response to chemotherapy.
TUCAN是一种含半胱天冬酶募集结构域（CARD）的蛋白质，通过调节细胞凋亡和NFκB途径参与肿瘤生物学过程。抑制半胱天冬酶-9可能导致耐药性。本研究评估了TUCAN在接受化疗的非小细胞肺癌（NSCLC）患者肿瘤中的表达模式、定位及预后价值。
采用免疫组织化学方法，对49例接受新辅助化疗（32例IIB期或IIIA期）或姑息化疗（17例IIIB期或IV期）的NSCLC患者的肿瘤标本进行TUCAN表达及定位评估。评估TUCAN表达与亚细胞定位、主要患者特征、治疗反应及总生存期之间的相关性。
49例肿瘤标本中有34例（69%）可检测到TUCAN表达。在阳性染色标本中，观察到三种定位模式：5例（11%）显示仅细胞核定位，13例（27%）仅细胞质染色，15例（31%）显示细胞质和细胞核均有定位。TUCAN的定位与化疗反应之间无显著相关性。虽然TUCAN表达与预后无关，但有趣的是，TUCAN仅在细胞质中的定位预示着生存期较短（p = 0.027）。
我们的结果表明，尽管TUCAN对化疗反应缺乏预测价值，但其不同的定位可能是NSCLC的一个预后因素。
