Varadhachary Gauri R, Talantov Dmitri, Raber Martin N, Meng Christina, Hess Kenneth R, Jatkoe Tim, Lenzi Renato, Spigel David R, Wang Yixin, Greco F Anthony, Abbruzzese James L, Hainsworth John D
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
J Clin Oncol. 2008 Sep 20;26(27):4442-8. doi: 10.1200/JCO.2007.14.4378.
To evaluate the feasibility of a 10-gene reverse transcriptase polymerase chain reaction assay to identify the tissue of origin in patients with carcinoma of unknown primary (CUP) site.
Diagnostic biopsy formalin-fixed, paraffin-embedded (FFPE) specimens from 120 patients with CUP were collected retrospectively from Sarah Cannon Research Institute, Nashville, TN, and prospectively from The University of Texas M. D. Anderson Cancer Center, Houston, TX. Tissue of origin assignments by the assay were correlated with clinical and pathologic features and with response to therapy.
The assay was successfully performed in 104 patients (87%), and a tissue of origin was assigned in 63 patients (61%). In the remaining 41 patients (39%), the molecular profiles were not specific for the six tumor types detectable by this assay. The tissues of origin most commonly identified were lung, pancreas, and colon; most of these patients had clinical and pathologic features consistent with these diagnoses. Patients with lung and pancreas profiles had poor response to treatment. Patients with colon cancer profiles had better response to colon cancer-specific therapies than they did to empiric CUP therapy with taxane/platinum regimens. Patients with ovarian cancer profiles were atypical, with widespread visceral metastases and a paucity of overt peritoneal involvement.
This gene expression profiling assay was feasible using FFPE biopsy specimens and identified a putative tissue of origin in 61% of patients with CUP. In most patients, the assigned tissue of origin was compatible with clinicopathologic features and response to treatment. Prospective studies in which assay results are used to direct therapy are indicated.
评估一种10基因逆转录聚合酶链反应检测法在确定原发灶不明癌（CUP）患者肿瘤组织来源方面的可行性。
回顾性收集了田纳西州纳什维尔市莎拉·坎农研究所120例CUP患者的福尔马林固定、石蜡包埋（FFPE）诊断活检标本，并前瞻性收集了得克萨斯大学MD安德森癌症中心（位于得克萨斯州休斯顿市）的此类标本。该检测法对组织来源的判定结果与临床和病理特征以及治疗反应进行了相关性分析。
104例患者（87%）成功进行了检测，63例患者（61%）确定了组织来源。其余41例患者（39%）的分子谱对该检测法可检测的六种肿瘤类型不具有特异性。最常确定的组织来源是肺、胰腺和结肠；这些患者中的大多数具有与这些诊断相符的临床和病理特征。具有肺和胰腺分子谱的患者对治疗反应较差。具有结肠癌分子谱的患者对结肠癌特异性疗法的反应比对紫杉烷/铂类方案的经验性CUP疗法更好。具有卵巢癌分子谱的患者情况不典型，有广泛的内脏转移且明显的腹膜受累较少。
使用FFPE活检标本进行这种基因表达谱检测是可行的，并且在61%的CUP患者中确定了假定的组织来源。在大多数患者中，确定的组织来源与临床病理特征及治疗反应相符。有必要开展前瞻性研究，将检测结果用于指导治疗。
