title: Endometrial carcinomas with significant mucinous differentiation associated with higher frequency of k-ras mutations: a morphologic and molecular correlation study.
abstract: OBJECTIVE
  K-ras gene product in the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway is critical in the development of certain types of malignancies. K-ras mutation-associated pancreatic and ovarian carcinomas often display mucinous differentiation. Previous studies have shown that k-ras mutation is found in 10% to 30% of endometrial carcinomas. We investigated k-ras mutations in several morphologic subtypes of endometrial carcinomas with particular emphasis on various degrees of mucinous differentiation.
  
  
  METHODS
  Genomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue sections. Polymerase chain reaction amplification for k-ras codons 12 and 13 were performed, followed by sequencing using capillary electrophoresis. The Fisher exact test is used to compare the prevalent difference of k-ras mutation among the groups. P < 0.05 was considered significant.
  
  
  RESULTS
  K-ras mutations were detected in 8 (80%) of 10 mucinous carcinomas, 12 (67%) of 18 endometrioid carcinomas (ECs) with significant mucinous differentiation (ECMD), 4 (25%) of 16 ECs, and 1 (9%) of 11 serous carcinomas. The differences were statistically significant between mucinous carcinomas versus EC (P < 0.01) and ECMD versus EC (P < 0.05).
  
  
  CONCLUSIONS
  The findings suggest that mucinous carcinoma and endometrioid carcinoma with significant mucinous component are more likely to be associated with k-ras mutation. Potential clinical implications of k-ras mutation lies in the management of recurrent or higher-stage endometrial mucinous tumors, which would not be responsive to treatment protocols containing epidermal growth factor receptor inhibitors.
authors.affiliation: Department of Pathology, Women & Infants Hospital of Rhode Island, Brown University, Providence, RI 02905, USA. jxiong@wihri.org
authors.forename: Jinjun
authors.initials: J
authors.lastname: Xiong
authors.forename: Mai
authors.initials: M
authors.lastname: He
authors.forename: Cynthia
authors.initials: C
authors.lastname: Jackson
authors.forename: Joyce J
authors.initials: JJ
authors.lastname: Ou
authors.forename: C James
authors.initials: CJ
authors.lastname: Sung
authors.forename: Virgina
authors.initials: V
authors.lastname: Breese
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Steinhoff
authors.forename: M Ruhul
authors.initials: MR
authors.lastname: Quddus
authors.forename: Trevor
authors.initials: T
authors.lastname: Tejada-Berges
authors.forename: W Dwayne
authors.initials: WD
authors.lastname: Lawrence
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics*; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000473:pathology; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D009154:Mutation / Q000235:genetics*; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins