Mutational analysis of tumors is becoming an important factor in the clinical care of cancer patients. Drug selection is often determined by the presence or absence of a particular genetic mutation. For example, breast cancer patients with tumors overexpressing the ERRB2 cell surface growth factor receptor have improved responses to targeted therapy with trastuzumab [1
Although imaging-guided core needle biopsy has become the accepted minimally invasive technique for histopathologic diagnosis, it is uncertain whether core needle biopsy yields sufficient and reliable material for mutational analysis. Ellis et al. [8
] reported that in breast tissue, single-pass core biopsy with a 14-gauge needle yielded a median of 1.34 μg of total RNA, sufficiently greater than the 1 μg of RNA required for microarray analysis. In that study, core needle biopsy yielded suitable material for RNA analysis 93% of the time. In a study of core biopsy of the breast [9
], sufficient material was obtained in only 75% of cases. All of the biopsies in those two studies were performed with relatively larger-gauge needles than are used in biopsy of tissue other than breast. Chen et al. [6
], however, found it possible to perform EGFR
mutational analysis of lung cancer with three cores obtained with an 18-gauge core biopsy needle. However, their results were not validated with the reference standard surgical specimen.
Another challenge at imaging-guided core needle biopsy is the risk of sampling error, which occurs when a tumor is composed of distinct cell populations. Needle biopsy sampling error in standard pathologic analysis has been reported [10
], showing that different parts of a tumor can have different genetic expressions.
In this study, we prospectively compared the results of mutational analysis of specimens obtained from lung cancer patients at imaging-guided 18- and 20-gauge core needle biopsy with the results of analysis of specimens obtained at surgical resection. There was 100% agreement (16 of 16 cases) in mutational analysis results for the two types of specimens when satisfactory material was present. Although the study had a relatively small sample size, the data suggest that imaging-guided core biopsy can be used reliably to obtain molecular information for guiding therapy, even when thin needles (18- or 20-gauge) are used. The needle samples in our study contained approximately 2 μg of material, which is satisfactory for analysis. Although other investigators [8
] found high correlation using 14-gauge breast biopsy needles, the results of our study suggest broader applicability of core needle biopsy to tissue other than breast.
That there was complete agreement in our specimens suggests that the EGFR
mutation, believed to be an early event in the types of lung cancer studied, is not subject to substantial intratumor heterogeneity. This consistency is similar to breast tumor ERRB2
] and is in contrast to the heterogeneity of estrogen and progesterone receptors [12
Two of 18 specimens (11.1%) in this study were unsatisfactory for analysis. A number of explanations for unsatisfactory biopsy are possible. The two unsatisfactory specimens in our study were obtained with fluoroscopic guidance, and the lower tissue resolution of fluoroscopy than of CT may lead to uncertainty in needle tip localization. CT has greater tissue contrast resolution, and the 3D capability of the technique can increase confidence in needle placement [13
]. On-site cytologic inspection is another factor in higher success rates of diagnostic biopsy [14
] and may aid in additional yield of mutational analysis specimens.
This study was limited by its small sample size and focus on limited mutational analysis. Nevertheless, the 100% agreement with surgical specimens when adequate material was available suggests that core needle biopsy can yield sufficient and reliable samples for mutational analysis. In addition, the study sample consisted mainly of patients with adenocarcinoma because this tumor occurs more frequently in patients with a limited smoking history, which was one of the inclusion criteria for the study from which the patient sample was drawn. It is unlikely that this factor affected the results.
The ability to gain accurate mutational information from needle biopsy specimens is an important realization. With this understanding, the importance of needle biopsy is likely to increase with development of pharmacotherapy based on the genetic makeup of individual tumors rather than on morphologic histologic features alone.