D. Roife1,2, Y. Kang1, R. Zhang1, L. Wang3, B. Fang3, M. Katz1, J. Gershenwald1, C. Dinney4, J. Fleming1 1University Of Texas MD Anderson Cancer Center,Surgical Oncology,Houston, TX, USA 2University Of Texas Health Science Center At Houston,General Surgery,Houston, TX, USA 3University Of Texas MD Anderson Cancer Center,Thoracic And Cardiovascular Surgery,Houston, TX, USA 4University Of Texas MD Anderson Cancer Center,Urology,Houston, TX, USA 5University Of Texas MD Anderson Cancer Center,Melanoma,Houston, TX, USA
Introduction: Patient-derived xenografts have become a powerful tool for cancer research in recent decades. One of the most significant barriers to growing xenografts from patient tumors is the need for surgical resection of tumor tissue. Thus far, patient derived xenografts have been grown from tumor tissue obtained after surgical resection of the primary tumor, and occasionally from metastatic tumors, if surgery was medically warranted. However, many cancer patients never undergo surgery for a variety of reasons, and therefore they are never given the opportunity of having their tumor tissue grown for research purposes via xenografts. We hypothesized that xenograft tumors could be grown from smaller volumes of patient tissue, such as those obtained during diagnostic biopsies.
Methods: Surgical specimens were obtained after resection of primary or metastatic lesions of the following cancers: pancreatic adenocarcinoma, lung adenocarcinoma, bladder (transitional cell) carcinoma, and melanoma. At least 10 cases of each cancer were included in this study. These cases did not exclude any patient in regards to neoadjuvant treatment or clinical characteristics. To mimic clinical biopsies, small fragments of the surgical specimens were biopsied with a 22g needle and the needle contents were injected subcutaneously in immunocompromised mice. The tumor fragment from which the biopsy was taken was also implanted subcutaneously in the contralateral side of the same mouse as a control.
Results: Success rates of the traditional method of xenograft implantation ranged from 30-70%, similar to what is reported in the literature. Success rates of the experimental biopsy technique ranged from 10%-40%. Since the experimental biopsy technique demonstrated successful results, the study culminated with the first patient derived xenograft grown from a percutaneous, outpatient biopsy. A patient with metastatic pancreatic adenocarcinoma underwent percutaneous ultrasound-guided core needle biopsy of a liver lesion. We divided this core biopsy and implanted the fragments into three immunocompromised mice, all of which grew into large tumors in under two months.
Conclusion: The lower success rate of the experimental biopsy technique was to be expected due to the smaller volume of tumor tissue implanted. However, it should be noted that these biopsy derived tumors reached comparable sizes as traditionally implanted tumor fragments in the same time frame, despite implanting significantly fewer cells. Also, metastatic tumor sites had much higher successful engraftment rates than samples taken from the primary tumor site. In conclusion, we have shown that it is possible to successfully grow patient-derived xenografts with small volumes of tumor samples that are obtainable during diagnostic biopsies, which potentially can open the xenograft technique to a wider scope of cancer patients.