title: A cautious view of putative precursors of serous carcinomas in the fallopian tubes of BRCA mutation carriers.
abstract: OBJECTIVE
  To compare the frequency and distribution of candidate precursors of serous carcinoma in the fallopian tubes of BRCA mutation carriers to BRCA non-mutation carriers (controls) at risk-reducing bilateral salpingo-oophorectomy (RRSO).
  
  
  METHODS
  78 BRCA carriers (52 BRCA1, 26 BRCA2) and 23 controls underwent RRSO. Fallopian tubes were serially cross-sectioned, and adnexa were entirely submitted and examined by two gynecologic pathologists blinded to BRCA mutation status. The presence and location of serous tubal intraepithelial carcinoma (STIC), p53 overexpression (≥ 6 consecutively stained nuclei), Ki67 overexpression, atypia/low grade dysplasia and epithelial hyperplasia were compared between BRCA carriers and controls. Patient age was dichotomized: ≤ 50 and >50 years.
  
  
  RESULTS
  9 (12%) BRCA carriers had occult carcinoma: 8 STIC and 1 stage IC tubal carcinoma with STIC. No occult carcinomas or STIC was seen in controls. STIC involved the distal tube in all cases and was multifocal in three cases. STIC was more common in women >50 (p=0.06). P53 overexpression was common in BRCA carriers (30%) and controls (43%) (p=0.5) and did not correlate with age. Only 5/9 (55%) of STIC exhibited p53 overexpression. 2 patients had Ki67 overexpression: both BRCA1 carriers with STIC. No difference in the frequency of atypia/low grade dysplasia or hyperplasia was observed between BRCA carriers and controls.
  
  
  CONCLUSIONS
  STIC is the dominant precursor of serous fallopian tube carcinoma in BRCA carriers. There is insufficient evidence to support p53 overexpression alone as a putative precursor. Atypia/low grade dysplasia and epithelial hyperplasia are not pre-neoplastic lesions of serous fallopian tube carcinoma.
authors.affiliation: Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, USA; Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Electronic address: cassi@cshs.org.
authors.forename: Ilana
authors.initials: I
authors.lastname: Cass
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Ann E
authors.initials: AE
authors.lastname: Walts
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Denise
authors.initials: D
authors.lastname: Barbuto
authors.affiliation: Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, USA; Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Jenny
authors.initials: J
authors.lastname: Lester
authors.affiliation: Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, USA; Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Karlan
mesh_terms: D000328:Adult; D000368:Aged; D002278:Carcinoma in Situ / Q000235:genetics* / Q000473:pathology; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000473:pathology; D005185:Fallopian Tube Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D011230:Precancerous Conditions / Q000235:genetics; D012189:Retrospective Studies
keywords: BRCA; Fallopian tube; Serous tubal intraepithelial carcinoma; p53 signature