Emerging Biopsy Tools Could Change Pathological Analysis

Recognizing the genetic heterogeneity of tumors, researchers are developing new biopsy tools that aim to expand the spatial diversity of sample collection, while simultaneously lessening the invasiveness of the biopsy procedure. These new techniques, if adopted into surgical practice, have the potential to alter laboratory workflow and pathological analysis not only in terms of the quantity of samples retrieved and sent for analysis but also in terms of the progressively more complex nature of interpreting the increasingly sensitive molecular findings in a clinically applicable manner. Keri Donaldson, M.D., medical director of molecular diagnostics at Penn State Milton S. Hershey Medical Center (Hershey, Pa.) explains to DTET that these technologies are designed to decrease sample selection error, increase the area of an organ surveyed, and increase the sensitivity of the biopsy procedure, but may pose a challenge for clinicians to apply the increasingly complex, mutifocal data to influence treatment decisions. Among the emerging technologies that rely upon an increased number of microsamples are microgrippers developed by researchers at Johns Hopkins University. The microgrippers are submillimeter, untethered tools that retrieve tissue samples, initially from the gastrointestinal tract. The researchers say that they represent a statistically more efficient means to screen large-area organs’ tissue, with samples that are suitable for either conventional cytologic analysis or genetic analysis. “Historically speaking, scientists are more optimistic than warranted, but there is clearly room for cutting-edge engineering in medicine,” says Florin Selaru, an assistant professor of gastroenterology and hepatology at Johns Hopkins School of Medicine. “There is a move towards miniaturization of tools that are minimally invasive but with a higher sensitivity of diagnosis. These techniques can redefine disease as we know it by finding more variety in diseases that we currently bulk together and oversimplify.” Sealru says the microgrippers could represent a clinical improvement in colonoscopies, which typically utilize a much larger forceps to remove 30 to 40 pieces of tissue. But despite the physician’s best intentions, the limited number of specimens may miss diseased or precancerous lesions. “What’s the likelihood of finding the needle in the haystack?” said Selaru. “Based on a small sample, you can’t always draw accurate inferences. We need to be able to do a larger statistical sampling of the tissue. . . . We could deploy hundreds or even thousands of these grippers to get more samples and a better idea of what kind of or whether a disease is present.” In addition to colonoscopies, particularly in ulcerative colitis or other higher-risk patients, the microgrippers may have applications in esophageal cancers and potentially outside of oncology in other disorders where diagnosis is based on spotty lesions that are difficult to see endoscopically, Selaru says. The researchers are working on improving the delivery of the microgrippers, but prior to a biopsy, the grippers are kept cold, so that the fingers remain in this extended position. Within five minutes of insertion, body heat leads to a softening of the polymer coating resulting in the inward curling of fingers, which then grasp some tissue. A magnetic tool is then inserted to retrieve them. Future iterations may include a color-coding of the grippers to improve location-based identification of samples. The higher volume of samples, Donaldson says, does not concern him, but he would be concerned about the potential increase in cost for analysis of additional samples and the translation of this additional molecular information (i.e., an increase in the percentage of subclones detected) into clinically meaningful data that clinicians can apply to treatment decisions. Down the road, this increased sensitivity to detect molecular alterations could transform diagnostics from a binary—positive or negative—molecular outcome (is it EGFR-positive or -negative?) to a percent expression score, but he cautions translation of these new reporting methods into practice is likely years off. Takeaway: New biopsy technologies aimed at increasing the diversity of sample selection will alter laboratory workflow and pathological analysis, potentially increasingly the complexity of interpreting molecular findings.  Side Box: Other Emerging Biopsy Technologies Other emerging biopsy tools focus on improving surgical margins and noninvasive sampling, both of which are biopsy trends that could impact pathological practice, experts say. Blaze Bioscience (Seattle)uses tumor paint to improve real-time intraoperative visualization of cancer cells. The paint uses a targeting peptide, which binds to the cancer cells, and a fluorescent dye, which emits light in the near-infrared range. The company is initiating its first phase 1 clinical study of the tumor paint product candidate, BLZ-100, at two sites in Australia, melanoma to evaluate the safety, tolerability, and pharmacokinetics of BLZ-100 after injection during surgery. Blaze closed a second round of financing of $9 million, primarily from existing angel funders, to finance the trials. By the end of 2014, the company anticipates initiating a U.S. clinical program for additional solid tumor types. DermTech (San Diego) analyzes noninvasively collected samples of suspected melanoma (on specialized tape) for specific RNA signatures on a high-throughput  quantitative polymerase chain reaction platform, rather than relying on histopathological analysis of surgically removed skin biopsies. The company initiated commercial  validation testing of its proprietary pigmented lesion assay in its CLIA-certified laboratory at the end of September 2013. Funds raised from a $5.6 million series B round (closed in August 2013) are financing these efforts.