Erin A Blake1,2, Malcolm S Ross3, Megan E Ross4, Koji Matsuo5, Emily T Silverstein6, Lilibeth R Torno7,8, Rohit Bhargava9, Miriam D Post10, Diane M Da Silva11, Sarah Taylor3, Saloni Walia12, Lynda Roman5, Troy A McEachron13. 1. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA. Erin.Blake@med.usc.edu. 2. Department of Gynecologic Oncology, University of Southern California, 2020 Zonal Ave., Room 522, Los Angeles, CA, 90033, USA. Erin.Blake@med.usc.edu. 3. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. 4. Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, CO, USA. 5. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA. 6. Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA. 7. Hyundai Cancer Genomics Center, Children's Hospital of Orange County, Orange, CA, USA. 8. Department of Pediatrics, School of Medicine, University of California-Irvine, Orange, CA, USA. 9. Division of Pathology, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. 10. Department of Pathology, University of Colorado School of Medicine, Aurora, CO, USA. 11. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, USA. 12. Department of Laboratory Medicine and Pathology, Department of Gynecologic Oncology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. 13. Department of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Abstract
OBJECTIVE: To validate our previous findings of high-level EGFR expression in GCCC using an expanded cohort of specimens and to further examine the molecular and cellular features of this aggressive malignancy to identify potentially actionable therapeutic targets. METHODS: The SEER database was queried to obtain the epidemiological data regarding the current national survival trends for GCCC. Immunohistochemistry (IHC) was used to examine the expression of EGFR, PD-1, and PD-L1. CiberSort analysis was used to analyze a previously published RNA-sequencing dataset obtained from a single patient diagnosed with GCCC. RESULTS: In comparison to squamous cell carcinomas and adenocarcinoma/adenosquamous carcinomas, GCCC was observed in younger patients (p < 0.001) and demonstrated inferior survival (p < 0.001). All (100%) of the specimens (8/8) exhibited immunoreactivity when stained for CD3ε (T-cell marker), EGFR, PD-1, and PD-L1 whereas CTLA4 expression was not detected. Analysis of RNA-sequencing data revealed that cetuximab and erlotinib altered the chemokine profile, lymphocyte abundance, and expression of inhibitory immune checkpoints in a single patient when combined with cytotoxic chemotherapy in a single patient. CONCLUSIONS: The data from this descriptive study suggests that immune checkpoint blockade, whether single agent or in combination, may be a suitable therapeutic option for a disease for which targeted approaches do not currently exist.
OBJECTIVE: To validate our previous findings of high-level EGFR expression in GCCC using an expanded cohort of specimens and to further examine the molecular and cellular features of this aggressive malignancy to identify potentially actionable therapeutic targets. METHODS: The SEER database was queried to obtain the epidemiological data regarding the current national survival trends for GCCC. Immunohistochemistry (IHC) was used to examine the expression of EGFR, PD-1, and PD-L1. CiberSort analysis was used to analyze a previously published RNA-sequencing dataset obtained from a single patient diagnosed with GCCC. RESULTS: In comparison to squamous cell carcinomas and adenocarcinoma/adenosquamous carcinomas, GCCC was observed in younger patients (p < 0.001) and demonstrated inferior survival (p < 0.001). All (100%) of the specimens (8/8) exhibited immunoreactivity when stained for CD3ε (T-cell marker), EGFR, PD-1, and PD-L1 whereas CTLA4 expression was not detected. Analysis of RNA-sequencing data revealed that cetuximab and erlotinib altered the chemokine profile, lymphocyte abundance, and expression of inhibitory immune checkpoints in a single patient when combined with cytotoxic chemotherapy in a single patient. CONCLUSIONS: The data from this descriptive study suggests that immune checkpoint blockade, whether single agent or in combination, may be a suitable therapeutic option for a disease for which targeted approaches do not currently exist.
Authors: P Littman; P B Clement; B Henriksen; C C Wang; S J Robboy; P D Taft; H Ulfelder; R E Scully Journal: Cancer Date: 1976-05 Impact factor: 6.860
Authors: Troy A McEachron; Leonard S Sender; Keri B Zabokrtsky; Brian Kaltenecker; W Nathan Holmes; Irene Cherni; Zarko Manojlovic; Shu-Yuan Liao; David W Craig; John D Carpten; Lilibeth R Torno Journal: J Adolesc Young Adult Oncol Date: 2016-03-14 Impact factor: 2.223