Department of Neuropathology, Institute of Pathology, Ruprecht-Karls University Heidelberg, 69120 Heidelberg INF 220, Germany.
Oncologist. 2011;16(2):165-74. doi: 10.1634/theoncologist.2010-0305. Epub 2011 Jan 27.
Identification of the tissue of origin of a brain metastatic tumor is vital to its management. Carcinoma of unknown primary (CUP) is common in oncology, representing 3%-5% of all invasive malignancies. We aimed to validate a recently developed microRNA-based quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) test for identifying the tumor tissue of origin, first in a consecutive cohort of metastatic tumors of known origin and then in a cohort of CUP cases resected from the central nervous system (CNS).
One hundred two resected CNS metastatic tumors with known origin, previously classified based on the patient's clinical history and pathological data, as well as a second cohort of resected CNS tumors from 57 patients originally diagnosed as CUP were studied. A qRT-PCR diagnostic assay that measures the expression level of 48 microRNAs was used to classify the tissue of origin of these metastatic tumors.
In this blinded study, the test predictions correctly identified the reference diagnosis of the samples of known origin, excluding samples from prostate origin, in 84% of cases. In the second CUP patient cohort, the test prediction was in agreement with the diagnosis that was later confirmed clinically or with pathological evaluation in 80% of cases.
In a cohort of brain and spinal metastases, a previously developed test based on the expression of 48 microRNAs allowed accurate identification of the tumor tissue of origin in the majority of cases. The high accuracy of this test in identifying the tissue of origin of metastases of unknown primary is demonstrated for the first time and may have broad clinical application.
确定脑转移瘤的组织来源对于其治疗至关重要。原发灶不明癌（CUP）在肿瘤学中很常见，占所有侵袭性恶性肿瘤的 3%-5%。我们旨在验证一种最近开发的基于 microRNA 的定量逆转录聚合酶链反应（qRT-PCR）检测方法，用于识别肿瘤组织来源，首先在已知来源的转移性肿瘤连续队列中进行，然后在中枢神经系统（CNS）切除的 CUP 病例队列中进行。
研究了 102 例经证实来源于 CNS 的转移性肿瘤，这些肿瘤之前根据患者的临床病史和病理数据进行了分类，以及第二组来自 57 例最初被诊断为 CUP 的 CNS 肿瘤的患者。使用测量 48 种 microRNA 表达水平的 qRT-PCR 诊断检测来对这些转移性肿瘤的组织来源进行分类。
在这项盲法研究中，该检测在排除前列腺来源样本的情况下，正确地预测了已知来源样本的参考诊断，在 84%的病例中。在第二个 CUP 患者队列中，在 80%的病例中，检测预测与后来临床或病理评估确认的诊断相符。
在脑和脊髓转移瘤队列中，先前基于 48 种 microRNA 表达开发的检测方法在大多数情况下可以准确识别肿瘤的组织来源。该检测方法在识别未知原发性转移的组织来源方面具有很高的准确性，这是首次得到证实，并可能具有广泛的临床应用。
