doi:10.1016/j.ygyno.2008.05.010 
Copyright © 2008 Elsevier Inc. All rights reserved.
Chromosomal instability in fallopian tube precursor lesions of serous carcinoma and frequent monoclonality of synchronous ovarian and fallopian tube mucosal serous carcinoma
Shannon Salvadora, 
, 1, 
, Allan Rempelb, 1, Robert A. Soslowc, Blake Gilksb, David Huntsmanb, d and Dianne Millere
aDepartment of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada
bDepartment of Pathology, University of British Columbia, Vancouver, BC, Canada
cDepartment of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA
dGenetic Pathology Evaluation Centre of the Prostate Centre and Department of Pathology of Vancouver Coastal Health Research Institute, British Columbia Cancer Agency, and University of British Columbia, Vancouver, BC, Canada
eDepartment of Gynecology Oncology, Vancouver Coastal Health Authority, British Columbia Cancer Agency, BC, Canada
Received 3 April 2008.
Available online 1 July 2008.
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Abstract
Objectives
Pelvic serous carcinomas are classified according to the location of greatest mass of tumor as ovarian, peritoneal or fallopian tube. Recent studies suggest these cancers may arise in the fallopian tube. This study explores the relationship between ovarian cancers and fallopian tube mucosal involvement.
Methods
Sixteen consecutive cases of epithelial ovarian malignancy were prospectively identified and the fallopian tubes submitted in toto for histopathological examination for tubal mucosal involvement. Immunohistochemical staining for p53 and Ki-67, and fluorescent in situ hybridization (FISH) analysis for chromosomal copy number changes were performed on 10 cases. Three cases of mucosal epithelial abnormalities identified in risk-reducing salpingectomy specimens were similarly characterized.
Results
Of sixteen cases, twelve were high-grade serous carcinoma, stage III, and four cases were stage I, two borderline mucinous, one borderline serous, and one low-grade mucinous carcinoma. Ten cases of high-grade serous carcinoma showed either unilateral fallopian tube mucosal involvement (n = 7) or tubal obliteration ipsilateral to the dominant ovarian mass (n = 3), compared to none of the other carcinomas. FISH analysis showed similar copy number changes in the ovarian and fallopian tube mucosal carcinoma in 3 cases, suggesting a unifocal origin; one case had differences suggesting multifocal origin of cancer. One case had equivocal FISH results. From risk-reducing salpingectomy cases, the multiple foci of tubal intraepithelial carcinoma and focus of invasive carcinoma showed similar gene copy number changes within each case, suggesting monclonality. Both cases of epithelial atypia/dysplasia showed gene copy number changes.
Conclusions
Fallopian tube mucosal and ovarian tumors have similar genetic abnormalities in most cases, indicating a monoclonal origin that may originate either from the ovary, peritoneum or fallopian tube. In situ epithelial lesions of the fallopian tube from risk-reducing salpingectomies show gene copy abnormalities consistent with these being early lesions of serous carcinoma and suggest that chromosomal instability is a very early event in serous carcinogenesis.
Keywords: Pelvic serous carcinoma; Fallopian tube carcinoma; O">rigin of disease; Ovarian carcinoma
Fig. 1. a. Ovarian cancer with fallopian tube mucosal involvement: percent of cells showing polysomy (≥ 5 FISH signals/nucleus). Cases V1, V2, and V4 show monoclonality between the ovarian carcinoma and the fallopian tube mucosal carcinoma. b. Ovarian cancer with no fallopian tube mucosal involvement: percent of cells showing polysomy (≥ 5 FISH signals/nucleus). Case V6 shows polysomy in the ovarian carcinoma that was not present in the fallopian tube serosal implants. V7 show monoclonality of the tumors.
Fig. 2. Ovarian carcinomas with and without fallopian tube mucosal involvement: percent of cells showing monosomy (≤ 1 FISH signal/nucleus). Case V6 show 100% monosomy in chromosome 17 in the serosal implants that was not present in the ovarian carcinoma. The remaining cases displayed no monosomy relative to normal FT controls.
Fig. 3. Representative slides of case V1, tubal mucosal involvement seen in a. with tubal serosal (TS) and tubal mucosal (arrow) involvement, b. tubal mucosal involvement (arrow), c. tubal intraepithelial carcinoma, d. p53 immunostaining, e. Ki-67 immunostaining, f. abnormal aneusomic FISH results in a single cell with aneusomic chromosome 1 (gold), 8 (red), and 11 (green).
Fig. 4. Representative slides of case V10 a. left tubal intraepithelial carcinoma with invasion (inv) and two areas of TIC: TIC1 (✸) and TIC2 (♦), b. p53 staining, () indicates abrupt boundary between p53 positive lesion and benign-appearing p53 negative tubal epithelium, c. Ki-67 staining, d. invasive carcinoma from case V10, e. high power of area indicated by () in b showing abrupt change from normal appearing tubal epithelium to TIC, f. high power of TIC 2 in case V10, g. p53 staining of area of tumor cells within contralateral tubal lumen, h. high power showing case V10 with cytologically malignant groups of cells within the lumen of the contralateral fallopian tube.
Fig. 5. a. TIC and epithelial dysplasia identified in risk-reducing salpingectomy specimens: percent of cells showing polysomy (≥ 5 FISH signals/nucleus). Case V10 has no polysomy while V11 has three out of four chromosomes with polysomy and V12 has two out of four. Normal FT controls not shown. b. TIC and epithelial dysplasia identified in risk-reducing salpingectomy specimens: percent of cells showing monosomy (≤ 1 FISH signal/nucleus). Case V10 shows monosomey in both the left and right fallopian tube while V11 and 12 have no monosomy. Normal FT controls not shown.
Table 1.
Tubal involvement in ovarian cancer cases studied
Table 2.
Ovarian carcinoma, immunochemistry
Per 500 cells ◇p53 low ≤ 50% reactive.
high > 50% reactive.
^Ki-67 low ≤ 5% reactive.
intermediate > 5 and ≤ 50% reactive.
high > 50% reactive.
Table 3.
Lesions from BRCA mutation carriers, immunochemistry
Per 500 cells ◇p53 low ≤ 50% reactive.
high > 50% reactive.
^Ki-67 low ≤ 5% reactive.
intermediate > 5 and ≤ 50% reactive.
high > 50% reactive.
a adjacent = morphologically normal epithelium immediately adjacent to TIC/EAD.
b normal = morphologically normal epithelium distant from TIC/EAD.
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