Intratumoral heterogeneity and chemoresistance in nonseminomatous germ cell tumor of the testis
Metrics: PDF 1511 views | HTML 2282 views | ?
Mehmet Asim Bilen1, Kenneth R. Hess2, Matthew T. Campbell3, Jennifer Wang3, Russell R. Broaddus4, Jose A. Karam5, John F. Ward5, Christopher G. Wood5, Seungtaek L. Choi6, Priya Rao4, Miao Zhang4, Aung Naing7, Rosale General3, Diana H. Cauley3, Sue-Hwa Lin8, Christopher J. Logothetis3, Louis L. Pisters5, Shi-Ming Tu3
1Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA
2Department of Biostatistics the University of Texas MD Anderson Cancer Center, Houston, Texas, USA
3Department of Genitourinary Medical Oncology the University of Texas MD Anderson Cancer Center, Houston, Texas, USA
4Department of Pathology the University of Texas MD Anderson Cancer Center, Houston, Texas, USA
5Department of Urology the University of Texas MD Anderson Cancer Center, Houston, Texas, USA
6Department of Radiation Oncology the University of Texas MD Anderson Cancer Center, Houston, Texas, USA
7Department of Investigational Cancer Therapeutics the University of Texas MD Anderson Cancer Center, Houston, Texas, USA
8Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Shi-Ming Tu, email: [email protected]
Keywords: testicular cancer, intratumoral heterogeneity, chemoresistance, nonseminomatous germ cell tumor, next-generation sequencing
Received: August 15, 2016 Accepted: November 07, 2016 Published: November 16, 2016
Background: Nonseminomatous germ cell tumor of the testis (NSGCT) is largely curable. However, a small group of patients develop refractory disease. We investigated the hypothesis that intratumoral heterogeneity contributes to the emergence of chemoresistance and the development of refractory tumor subtypes.
Results: Our institution’s records for January 2000 through December 2010 included 275 patients whose primary tumor showed pure embryonal carcinoma (pure E); mixed embryonal carcinoma, yolk sac tumor, and teratoma (EYT); or mixed embryonal carcinoma, yolk sac tumor, seminoma, and teratoma (EYST). Patients with EYST had the highest cancer-specific mortality rate (P = .001). They tended to undergo somatic transformation (P = .0007). Two of 5 patients with clinical stage I EYST who had developed recurrence during active surveillance died of their disease.
Materials and Methods: In this retrospective study, we evaluated consecutive patients who had been diagnosed with the three most common histological phenotypes of NSGCT. Chemoresistance was defined as the presence of teratoma, viable germ cell tumor, or somatic transformation in the residual tumor or the development of progressive or relapsed disease after chemotherapy. In a separate prospective study, we performed next-generation sequencing on tumor samples from 39 patients to identify any actionable genetic mutations.
Conclusions: Our data suggest that patients with EYST in their primary tumor may harbor a potentially refractory NSGCT phenotype and are at increased risk of dying from disease. Despite intratumoral heterogeneity, improved patient selection and personalized care of distinct tumor subtypes may optimize the clinical outcome of patients with NSGCT.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.