PMID- 26913631
OWN - NLM
STAT- MEDLINE
DCOM- 20160908
LR  - 20220310
IS  - 2374-2445 (Electronic)
IS  - 2374-2437 (Linking)
VI  - 2
IP  - 4
DP  - 2016 Apr
TI  - Genetic Basis for PD-L1 Expression in Squamous Cell Carcinomas of the Cervix and 
      Vulva.
PG  - 518-22
LID - 10.1001/jamaoncol.2015.6326 [doi]
AB  - IMPORTANCE: Patients with squamous cell carcinoma (SCC) of the cervix or vulva 
      have limited therapeutic options, and the potential for immunotherapy for this 
      population has not been evaluated. Recent trials suggest that tumors with a 
      genetic basis for PD-1 (programmed cell death protein 1) ligand expression are 
      highly sensitive to therapeutic antibodies targeting PD-1. OBJECTIVE: To 
      determine the genetic status of CD274 (encoding PD-L1 [programmed cell death 1 
      ligand 1]) and PDCD1LG2 (encoding PD-L2 [programmed cell death 1 ligand 2]) in 
      SCCs of the cervix and vulva and to correlate the findings with PD-L1 protein 
      expression. DESIGN, SETTING, AND PARTICIPANTS: We performed fluorescence in situ 
      hybridization (FISH) using probes targeting CD274, PDCD1LG2, and the centromeric 
      portion of chromosome 9, and immunohistochemistry (IHC) using an antibody 
      recognizing PD-L1 on formalin-fixed, paraffin-embedded (FFPE) biopsy specimens 
      from 48 cervical SCCs and 23 vulvar SCCs. MAIN OUTCOMES AND MEASURES: Tumors were 
      categorized according to the genetic abnormality in CD274 and PDCD1LG2 
      (coamplification > cogain > polysomy > disomy) as detected by FISH, and evaluated 
      on a semiquantitative scale (modified H score, the product of the percentage of 
      tumor cells with positive staining and the maximum intensity of positive 
      staining) for PD-L1 protein expression as detected by IHC. RESULTS: Overall, 71 
      samples of FFPE tissue from cases of cervical SCCs (n = 48) and vulvar SCCs 
      (n = 23) were retrieved from the archives of Brigham and Women's Hospital and 
      included in this study. We observed cogain or coamplification of CD274 and 
      PDCD1LG2 in 32 of 48 cervical SCCs (67%) and 10 of 23 vulvar SCCs (43%). Median 
      PD-L1 protein expression was highest among tumors with CD274 and PDCD1LG2 
      coamplification and lowest among tumors with disomy. CONCLUSIONS AND RELEVANCE: 
      Recurrent copy number gain of the genes encoding the PD-1 ligands provides a 
      genetic basis for PD-L1 expression in a subset of cervical and vulvar SCCs and 
      identifies a class of patients that are rational candidates for therapies 
      targeting PD-1.
FAU - Howitt, Brooke E
AU  - Howitt BE
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
FAU - Sun, Heather H
AU  - Sun HH
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
FAU - Roemer, Margaretha G M
AU  - Roemer MG
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston 
      Massachusetts.
FAU - Kelley, Alyssa
AU  - Kelley A
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
FAU - Chapuy, Bjoern
AU  - Chapuy B
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston 
      Massachusetts.
FAU - Aviki, Emeline
AU  - Aviki E
AD  - Departments of Obstetrics and Gynecology, Radiation Oncology, and Gynecological 
      Oncology, Brigham and Women's Hospital, Boston, Massachusetts.
FAU - Pak, Christine
AU  - Pak C
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
FAU - Connelly, Courtney
AU  - Connelly C
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
FAU - Gjini, Evisa
AU  - Gjini E
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, 
      Massachusetts2Department of Medical Oncology, Dana-Farber Cancer Institute, 
      Boston Massachusetts4The Center for Immuno-Oncology, Dana-Farber Cancer 
      Institute, Boston, Massachusetts.
FAU - Shi, Yunling
AU  - Shi Y
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
FAU - Lee, Larissa
AU  - Lee L
AD  - Departments of Obstetrics and Gynecology, Radiation Oncology, and Gynecological 
      Oncology, Brigham and Women's Hospital, Boston, Massachusetts.
FAU - Viswanathan, Akila
AU  - Viswanathan A
AD  - Departments of Obstetrics and Gynecology, Radiation Oncology, and Gynecological 
      Oncology, Brigham and Women's Hospital, Boston, Massachusetts.
FAU - Horowitz, Neil
AU  - Horowitz N
AD  - Departments of Obstetrics and Gynecology, Radiation Oncology, and Gynecological 
      Oncology, Brigham and Women's Hospital, Boston, Massachusetts.
FAU - Neuberg, Donna
AU  - Neuberg D
AD  - Department of Biostatistics and Computational Biology, Dana-Farber Cancer 
      Institute, Boston, Massachusetts.
FAU - Crum, Christopher P
AU  - Crum CP
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
FAU - Lindeman, Neal L
AU  - Lindeman NL
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
FAU - Kuo, Frank
AU  - Kuo F
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
FAU - Ligon, Azra H
AU  - Ligon AH
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
FAU - Freeman, Gordon J
AU  - Freeman GJ
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston 
      Massachusetts4The Center for Immuno-Oncology, Dana-Farber Cancer Institute, 
      Boston, Massachusetts.
FAU - Hodi, F Stephen
AU  - Hodi FS
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston 
      Massachusetts4The Center for Immuno-Oncology, Dana-Farber Cancer Institute, 
      Boston, Massachusetts.
FAU - Shipp, Margaret A
AU  - Shipp MA
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston 
      Massachusetts4The Center for Immuno-Oncology, Dana-Farber Cancer Institute, 
      Boston, Massachusetts.
FAU - Rodig, Scott J
AU  - Rodig SJ
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts4The 
      Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
LA  - eng
GR  - CA161026/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - JAMA Oncol
JT  - JAMA oncology
JID - 101652861
RN  - 0 (B7-H1 Antigen)
RN  - 0 (CD274 protein, human)
RN  - 0 (PDCD1LG2 protein, human)
RN  - 0 (Programmed Cell Death 1 Ligand 2 Protein)
SB  - IM
MH  - B7-H1 Antigen/biosynthesis/*genetics
MH  - Carcinoma, Squamous Cell/*genetics
MH  - Female
MH  - Gene Dosage
MH  - Gene Expression Regulation, Neoplastic/genetics
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Programmed Cell Death 1 Ligand 2 Protein/*genetics
MH  - Uterine Cervical Neoplasms/*genetics
MH  - Vulvar Neoplasms/*genetics
EDAT- 2016/02/26 06:00
MHDA- 2016/09/09 06:00
CRDT- 2016/02/26 06:00
PHST- 2016/02/26 06:00 [entrez]
PHST- 2016/02/26 06:00 [pubmed]
PHST- 2016/09/09 06:00 [medline]
AID - 2492720 [pii]
AID - 10.1001/jamaoncol.2015.6326 [doi]
PST - ppublish
SO  - JAMA Oncol. 2016 Apr;2(4):518-22. doi: 10.1001/jamaoncol.2015.6326.