PMID- 32773531
OWN - NLM
STAT- MEDLINE
DCOM- 20201214
LR  - 20210131
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Linking)
VI  - 44
IP  - 11
DP  - 2020 Nov
TI  - Molecular Characterization of Neuroendocrine Carcinomas of the Endometrium: 
      Representation in All 4 TCGA Groups.
PG  - 1541-1548
LID - 10.1097/PAS.0000000000001560 [doi]
AB  - High-grade neuroendocrine carcinomas (NEC) of the endometrium are rare and 
      account for <1% of all endometrial carcinomas. Both small cell neuroendocrine 
      carcinoma (SCNEC) and large cell neuroendocrine carcinoma (LCNEC) morphologies 
      have been reported. Little is known regarding the molecular features of 
      endometrial NEC including how they compare to pulmonary NEC (the most common site 
      for these neoplasms) and the more common endometrial carcinoma histotypes. In 
      this study, we investigated the molecular alterations in a series of endometrial 
      NEC using a targeted next generation sequencing panel (Oncopanel). Fourteen NEC 
      were sequenced; pure NEC (n=4) and mixed (n=10) with endometrioid adenocarcinoma 
      (n=9) or carcinosarcoma (n=1). The NEC components of mixed tumors comprised LCNEC 
      (n=6) and SCNEC (n=4). The 4 pure NEC comprised LCNEC (n=2) and SCNEC (n=2). 
      Molecular analysis classified tumors into the 4 The Cancer Genome Atlas groups: 
      (1) POLE-mutated/ultramutated (1/14; 7%), (2) microsatellite 
      instability/hypermutated (6/14; 43%), (3) TP53 mutated/copy number high (2/14; 
      14%), or (4) no specific molecular profile (5/14; 36%). Overall, 50% of cases 
      were ultramutated or hypermutated. In 8 cases of mixed carcinomas, the different 
      histologic components were macrodissected and separately sequenced; molecular 
      alterations were nearly identical among the 2 components, with the non-NEC 
      component harboring slightly increased tumor mutational burden. Only 2 carcinomas 
      (both with pure SCNEC morphology) had a molecular profile that would be expected 
      in typical pulmonary SCNEC (RB1 deletion and TP53 mutations). Our findings, 
      similar to data from NECs of other anatomic sites, suggest that the molecular 
      context may be important when selecting therapies for women with endometrial NEC. 
      Immune checkpoint inhibition may be a reasonable approach to treatment of 
      microsatellite instability-NEC and we thus recommend that all endometrial NEC be 
      tested for mismatch repair abnormalities, either molecularly or by mismatch 
      repair protein immunohistochemistry.
FAU - Howitt, Brooke E
AU  - Howitt BE
AD  - Women's and Perinatal Pathology Division.
AD  - Department of Pathology, Stanford University School of Medicine, Stanford, CA.
FAU - Dong, Fei
AU  - Dong F
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, MA.
FAU - Vivero, Marina
AU  - Vivero M
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, MA.
FAU - Shah, Varsha
AU  - Shah V
AD  - Department of Pathology, Royal Gwent Hospital, Wales.
FAU - Lindeman, Neal
AU  - Lindeman N
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, MA.
FAU - Schoolmeester, J Kenneth
AU  - Schoolmeester JK
AD  - Mayo Clinic, Rochester, MN.
FAU - Baltay, Michele
AU  - Baltay M
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, MA.
FAU - MacConaill, Laura
AU  - MacConaill L
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, MA.
FAU - Sholl, Lynette M
AU  - Sholl LM
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, MA.
FAU - Nucci, Marisa R
AU  - Nucci MR
AD  - Women's and Perinatal Pathology Division.
FAU - McCluggage, W Glenn
AU  - McCluggage WG
AD  - Department of Pathology, Belfast Health and Social Care Trust, Belfast, UK.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Carcinoma, Neuroendocrine/*genetics/pathology
MH  - DNA Mutational Analysis
MH  - Endometrial Neoplasms/*genetics/pathology
MH  - Female
MH  - Humans
MH  - Middle Aged
EDAT- 2020/08/11 06:00
MHDA- 2020/12/15 06:00
CRDT- 2020/08/11 06:00
PHST- 2020/08/11 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2020/08/11 06:00 [entrez]
AID - 00000478-202011000-00014 [pii]
AID - 10.1097/PAS.0000000000001560 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2020 Nov;44(11):1541-1548. doi: 10.1097/PAS.0000000000001560.