title: KRAS Mutations in Mucinous Lesions of the Uterus.
abstract: OBJECTIVE
  The current study examined the KRAS mutation status in a spectrum of mucinous lesions of the uterus, including mucinous metaplasia (MM), atypical mucinous proliferation (AMP), endocervical mucosa, and microglandular hyperplasia (MGH).
  
  
  METHODS
  Thirty-nine cases, including 15 AMPs, nine MMs, nine MGHs, and six normal endocervical mucosas, were selected from the departmental archive. All AMP cases with follow-up biopsies or hysterectomies were reviewed. Genomic DNA was extracted from formalin-fixed, paraffin-embedded tissue and KRAS codons 12 and 13 sequence analyzed.
  
  
  RESULTS
  KRAS codon 12 and 13 mutations were detected in 10 (67%) of the 15 AMP cases. No KRAS mutations were identified in MMs, MGHs, and endocervical mucosas (P = .002, AMP vs MM or MGH, Fisher exact test). Most women with AMP were postmenopausal (13/15 [86.7%]) and presented with dysfunctional uterine bleeding. Among the 10 cases of AMP harboring KRAS mutations, six (60%) cases were subsequently diagnosed with carcinoma, one with atypical complex hyperplasia, and two with AMP within endometrial polyps.
  
  
  CONCLUSIONS
  The results suggest a possible association between KRAS mutations and mucinous differentiation in endometrial carcinogenesis. KRAS status can help in assessing benign from precursor or malignant mucinous lesions as well as differentiate endometrial lesions from those of cervical origin.
authors.affiliation: From the Department of Pathology and Laboratory Medicine, Women and Infants Hospital of Rhode Island, Providence; Warren Alpert Medical School of Brown University, Providence, RI; and Mai_he@brown.edu.
authors.forename: Mai
authors.initials: M
authors.lastname: He
authors.affiliation: Warren Alpert Medical School of Brown University, Providence, RI; and Clinical Molecular Biology Laboratory, Department of Pathology and Laboratory Medicine, Rhode Island Hospital, Providence.
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Jackson
authors.affiliation: From the Department of Pathology and Laboratory Medicine, Women and Infants Hospital of Rhode Island, Providence; Warren Alpert Medical School of Brown University, Providence, RI; and.
authors.forename: Rebecca Buell
authors.initials: RB
authors.lastname: Gubrod
authors.affiliation: Clinical Molecular Biology Laboratory, Department of Pathology and Laboratory Medicine, Rhode Island Hospital, Providence.
authors.forename: Virginia
authors.initials: V
authors.lastname: Breese
authors.affiliation: From the Department of Pathology and Laboratory Medicine, Women and Infants Hospital of Rhode Island, Providence; Warren Alpert Medical School of Brown University, Providence, RI; and.
authors.forename: Margaret
authors.initials: M
authors.lastname: Steinhoff
authors.affiliation: From the Department of Pathology and Laboratory Medicine, Women and Infants Hospital of Rhode Island, Providence; Warren Alpert Medical School of Brown University, Providence, RI; and.
authors.forename: W D
authors.initials: WD
authors.lastname: Lawrence
authors.affiliation: From the Department of Pathology and Laboratory Medicine, Women and Infants Hospital of Rhode Island, Providence; Warren Alpert Medical School of Brown University, Providence, RI; and.
authors.forename: Jinjun
authors.initials: J
authors.lastname: Xiong
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D042282:Microdissection; D009154:Mutation; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D014594:Uterine Neoplasms / Q000235:genetics* / Q000473:pathology; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: Atypical mucinous proliferation; Differential diagnosis; KRAS; Management; Pathogenesis; Uterine mucinous lesions