PMID- 32144339
OWN - NLM
STAT- MEDLINE
DCOM- 20201123
LR  - 20210919
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 10
IP  - 1
DP  - 2020 Mar 6
TI  - Loss of Estrogen Receptors is Associated with Increased Tumor Aggression in 
      Laryngeal Squamous Cell Carcinoma.
PG  - 4227
LID - 10.1038/s41598-020-60675-2 [doi]
LID - 4227
AB  - Laryngeal squamous cell carcinoma (LSCC) responds to 17beta-estradiol via 
      estrogen-receptor (ER, transcribed from ESR1) dependent mechanisms, but is not 
      recognized as a hormonally responsive cancer. 17beta-estradiol production by LSCC 
      cell lines UM-SCC-11A and UM-SCC-12 was examined. Wild type (WT) and 
      ESR1-silenced LSCC cultures and xenografts were examined for 17beta-estradiol 
      responsiveness in vivo. 14 LSCC and surrounding epithelial samples at various 
      pathological stages were obtained from patients; ERalpha and ERbeta expression were 
      verified using data from the total cancer genome atlas. UM-SCC-11A and UM-SCC-12 
      both produce 17beta-estradiol, but only UM-SCC-12, not UM-SCC-11A, xenograft tumors 
      grow larger in vivo in response to systemic 17beta-estradiol treatments. ERalpha66 and 
      ERalpha36 expression inversely correlated with clinical cancer stage and tumor 
      burden. LSCC ERalpha66 expression was higher compared to surrounding epithelia in 
      indolent samples but lower in aggressive LSCC. ERbeta expression was highly 
      variable. High ESR1 expression correlated with improved survival in LSCC. Loss of 
      ERalpha66 expression inversely correlated with prognosis in LSCC. ERalpha66 may be a 
      histopathological marker of aggression in LSCC.
FAU - Verma, Anjali
AU  - Verma A
AD  - Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, 
      VA, USA.
FAU - Schwartz, Nofrat
AU  - Schwartz N
AD  - Department of Otolaryngology, Meir Hospital, Kfar Saba, Israel.
AD  - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
AD  - Department of Otolaryngology - Head and Neck Surgery and Neurosurgery, University 
      of North Carolina School of Medicine, Chapel Hill, NC, USA.
FAU - Cohen, David J
AU  - Cohen DJ
AD  - Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, 
      VA, USA.
FAU - Patel, Vaidehi
AU  - Patel V
AD  - Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, 
      VA, USA.
FAU - Nageris, Benny
AU  - Nageris B
AD  - Department of Otolaryngology, Meir Hospital, Kfar Saba, Israel.
AD  - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
FAU - Bachar, Gideon
AU  - Bachar G
AD  - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
AD  - Department of Otolaryngology Head and Neck Surgery, Rabin Medical Center, 
      Petah-Tikvah, Israel.
FAU - Boyan, Barbara D
AU  - Boyan BD
AD  - Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, 
      VA, USA. bboyan@vcu.edu.
AD  - Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, 
      GA, USA. bboyan@vcu.edu.
FAU - Schwartz, Zvi
AU  - Schwartz Z
AD  - Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, 
      VA, USA.
AD  - Department of Periodontics, University of Texas Health Science Center at San 
      Antonio, San Antonio, TX, USA.
LA  - eng
GR  - P30 CA016059/CA/NCI NIH HHS/United States
GR  - UL1 TR001863/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200306
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (ESR1 protein, human)
RN  - 0 (ESR2 protein, human)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Estrogen Receptor beta)
RN  - 4TI98Z838E (Estradiol)
SB  - IM
MH  - Aged
MH  - Biomarkers, Tumor/genetics/*metabolism
MH  - Carcinoma, Squamous Cell/genetics/metabolism/*pathology
MH  - Estradiol/*metabolism
MH  - Estrogen Receptor alpha/*antagonists & inhibitors/genetics/metabolism
MH  - Estrogen Receptor beta/*antagonists & inhibitors/genetics/metabolism
MH  - Female
MH  - Follow-Up Studies
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Laryngeal Neoplasms/genetics/metabolism/*pathology
MH  - Male
MH  - Middle Aged
MH  - Prognosis
MH  - Tumor Cells, Cultured
PMC - PMC7060328
COIS- The authors declare no competing interests.
EDAT- 2020/03/08 06:00
MHDA- 2020/11/24 06:00
PMCR- 2020/03/06
CRDT- 2020/03/08 06:00
PHST- 2019/07/31 00:00 [received]
PHST- 2020/01/20 00:00 [accepted]
PHST- 2020/03/08 06:00 [entrez]
PHST- 2020/03/08 06:00 [pubmed]
PHST- 2020/11/24 06:00 [medline]
PHST- 2020/03/06 00:00 [pmc-release]
AID - 10.1038/s41598-020-60675-2 [pii]
AID - 60675 [pii]
AID - 10.1038/s41598-020-60675-2 [doi]
PST - epublish
SO  - Sci Rep. 2020 Mar 6;10(1):4227. doi: 10.1038/s41598-020-60675-2.