Highlights
- •STIC is the dominant precursor of pelvic serous carcinomas in BRCA mutation carriers.
- •Isolated p53 overexpression is not likely as a candidate precursor.
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.
Keywords
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References
- Transformation of the fallopian tube secretory epithelium leads to high-grade serous ovarian cancer in Brca;TP53;Pten models.Cancer Cell. 2013; 24: 751-765
- The distal fallopian tube: a new model for pelvic serous carcinogenesis.Curr Opin Obstet Gynecol. 2007; 19: 3-9
- Carcinoma of the fallopian tube: a clinicopathological study of 105 cases with observations on staging and prognostic factors.Gynecol Oncol. 1999; 72: 367-379
- Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: evidence for a causal relationship.Am J Surg Pathol. 2007; 31: 161-169
- Occult carcinoma in prophylactic oophorectomy specimens: prevalence and association with BRCA germline mutation status.Am J Surg Pathol. 2001; 25: 1283-1289
- Pathologic findings in prophylactic oophorectomy specimens in high-risk women.Gynecol Oncol. 2002; 87: 52-56
- Atypical epithelial proliferation in fallopian tubes in prophylactic salpingo-oophorectomy specimens from BRCA1 and BRCA2 germline mutation carriers.Int J Gynecol Pathol. 2003; 23: 35-40
- Risk-reducing salpingo-oophorectomy in BRCA mutation carriers: role of serial sectioning in the detection of occult malignancy.J Clin Oncol. 2005; 23: 127-132
- The tubal fimbria is a preferred site of early adenocarcinoma in women with familial ovarian cancer syndrome.Am J Surg Pathol. 2006; 30: 230-236
- Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 Mutation.JAMA. 2006; 296: 185-192
- Primary fallopian tube malignancies in BRCA-positive women undergoing surgery for ovarian cancer risk reduction.J Clin Oncol. 2007; 25: 3985-3990
- Risk-reducing salpingo-oophorectomy (RRSO) in BRCA mutation carriers: experience with consecutive series of 111 patients using a standardized surgical–pathological protocol.Int J Gynecol Cancer. 2011; 21: 846-851
- A candidate precursor to serous carcinoma that originates in the distal fallopian tube.J Pathol. 2007; 211: 26-35
- Lessons from BRCA: the tubal fimbria emerges as an origin for pelvic serous carcinomas.Clin Med Res. 2007; 5: 35-44
- Modeling high-grade serous ovarian carcinogenesis from the fallopian tube.Proc Natl Acad Sci. 2011; 108: 7547-7552
- High-grade serous ovarian cancer arises from fallopian tube in a mouse model.Proc Natl Acad Sci. 2012; 109: 3921-3926
- Integrated genomic analysis of ovarian carcinoma. Cancer Genomic Atlas Research Network.Nature. 2011; 474: 609-615
- Candidate serous cancer precursors in fallopian tube epithelium of BRCA1/2 mutation carriers.Mod Pathol. 2009; 22: 1133-1138
- The molecular pathogenesis of hereditary ovarian carcinoma.Cancer. 2010; 116: 5261-5271
- High-grade fimbrial-ovarian carcinomas are unified by altered p53, PTEN, and PAX2 expression.Mod Pathol. 2010; 23: 1316-1324
- Tubal epithelial lesions in salpingo-oophorectomy specimens of BRCA-carriers and controls.Gynecol Oncol. 2012; 127: 88-93
- Mucosal epithelial proliferation of the fallopian tube: prevalence, clinical associations, and optimal strategy for histopathologic assessment.Int J Gynecol Pathol. 2000; 19: 139-144
- Dysplastic changes in prophylactically removed fallopian tubes of women predisposed to developing ovarian cancer.J Pathol. 2001; 195: 451-456
- Diagnosis of serous tubal intraepithelial carcinoma based upon morphologic immunohistochemical features: a reproducibility study.Am J Surg Pathol. 2011; 35: 1766-1775
- Risk factors for non-invasive lesions if the fallopian tube in BRCA mutation carriers.Gynecol Oncol. 2010; 118: 295-298
- A candidate precursor to pelvic serous cancer (p53 signature) and its prevalence in ovaries and fallopian tubes from women with BRCA mutations.Gynecol Oncol. 2008; 109: 168-173
- Risk factors for serous precursor cancer (“p53 signature”) in women with inherited BRCA mutations.Gynecol Oncol. 2008; 111: 226-232
- Serous tubal intraepithelial carcinoma: diagnostic reproducibility and its implications.Int J Gynecol Pathol. 2010; 29: 310-314
- Primary fallopian tube adenocarcinoma in situ with adjuvant therapy for breast carcinoma.Gynecol Oncol. 1994; 52: 402-407
- Mucosal epithelial proliferation of the fallopian tube: a particular association with ovarian serous tumor of low malignant potential?.Int J Gynecol Pathol. 1995; 14: 107-113
- Pseudocarcinomatous hyperplasia of the fallopian tube associated with salpingitis: a report of 14 cases.Am J Surg Pathol. 1994; 18: 1125-1130
- Pseudocarcinomatous hyperplasia of the fallopian tubes which was associated with female genital tract tuberculosis, histologically mimicking tubal adenocarcinoma: a diagnostic challenge.J Clin Diagn Res. 2012; 6: 1419-1421
- A prospective study of risk-reducing salpingo-oophorectomy and longitudinal CA-125 screening among women at increased genetic risk of ovarian cancer: design and baseline characteristics: a Gynecologic Oncology Group study.Cancer Epidemiol Biomarkers Prev. 2008; 17: 594-604
- BRCA-mutation-associated fallopian tube carcinoma.Obstet Gynecol. 2010; 106: 1327-1334
- Prophylactic salpingectomy in premenopausal low-risk women for ovarian cancer: primum non nocere.Gynecol Oncol. 2013; 129: 448-451
- Does bilateral salpingectomy with ovarian retention warrant consideration as a temporary bridge to risk-reducing bilateral oophorectomy in BRCA1/2 mutation carriers?.Am J Obstet Gynecol. 2011; 204: 19.e1-19.e6
- Prophylactic salpingectomy and delayed oophorectomy as an alternative for BRCA mutation carriers.Obstet Gynecol. 2013; 121: 14-24
Article info
Publication history
Published online: July 12, 2014
Accepted:
July 8,
2014
Received:
April 10,
2014
Identification
Copyright
© 2014 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
