title: Alteration in PI3K/mTOR, MAPK pathways and Her2 expression/amplification is more frequent in uterine serous carcinoma than ovarian serous carcinoma.
abstract: OBJECTIVE
  To compare the molecular profile of a large cohort of uterine papillary serous carcinoma (UPSC) and ovarian serous carcinoma (EOC-S).
  
  
  METHODS
  628 UPSC and 5335 EOC-S tumors were evaluated using a commercial multiplatform profiling service (CARIS Life Sciences, Phoenix, AZ). Specific testing performed included a combination of gene sequencing (Sanger, next generation sequencing), protein expression (IHC) and gene amplification (CISH or FISH).
  
  
  RESULTS
  TP53 was the most commonly mutated gene in both UPSC and EOC-S (76% vs. 69%, P = 0.03). UPSC were more likely to have mutation in PIK3CA (29% vs. 2%, P < 0.001), FBXW7 (12% vs. 1%, P < 0.001), KRAS (9% vs. 5%, P < 0.001) PTEN (7% vs. 1%, P < 0.001), and CTNNB1 (2% vs. 0%, P < 0.001) compared to EOC-S. On the other hand, EOC-S were more likely to harbor mutation in BRCA1 (20% vs. 9% P = 0.17) and BRCA2 (18% vs. 6% P = 0.09). HER2 gene amplification (17% vs. 4%, P < 0.001) and Her2/neu expression (10% vs. 2%, P < 0.001) were more frequent in UPSC than EOC-S, respectively.
  
  
  CONCLUSIONS
  UPSC have a distinct mutation profile indicating higher activity of PI3K/AKT/mTOR, and MAPK pathways and Her2 expression/amplification but a trend toward lower frequency of alteration in homologous recombination pathway compared to EOC-S. Targeted PI3K/AKT/mTOR inhibitors should be evaluated in UPSC.
authors.affiliation: Gynecologic Oncology division, Ob/Gyn and Women's Health Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Haider
authors.initials: H
authors.lastname: Mahdi
authors.affiliation: CARIS Life Sciences, Phoenix, Arizona.
authors.forename: Joanne
authors.initials: J
authors.lastname: Xiu
authors.affiliation: CARIS Life Sciences, Phoenix, Arizona.
authors.forename: Sandeep K
authors.initials: SK
authors.lastname: Reddy
authors.affiliation: Gynecologic Oncology division, Ob/Gyn and Women's Health Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Robert
authors.initials: R
authors.lastname: DeBernardo
mesh_terms: D000328:Adult; D000368:Aged; D018284:Cystadenocarcinoma, Serous / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D020935:MAP Kinase Signaling System; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009154:Mutation; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012189:Retrospective Studies; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D059467:Transcriptome; D014594:Uterine Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human; C508053:ERBB2 protein, human
keywords: BRCA; CARIS; HER2/neu; PI3K/AKT/mTOR; molecular profile; serous ovarian carcinoma; uterine papillary serous carcinoma