Abstract
The aim of this study was to investigate the occurrence of (pre)neoplastic lesions in overtly normal Fallopian tubes from women predisposed to developing ovarian carcinoma. The presence of (pre)neoplastic lesions was scored in histological specimens from 12 women with a genetically determined predisposition for ovarian cancer, of whom seven tested positive for a germline BRCA1 mutation. A control group included 13 women. Immunohistochemistry was used to determine the expression of p21, p27, p53, cyclin A, cyclin D1, bcl-2, Ki67, HER-2/neu, and the oestrogen and progesterone receptors. Loss of heterozygosity (LOH) analysis on the BRCA1 locus was also assessed on dysplastic tissue by PCR studies. Of the 12 women with a predisposition for ovarian cancer, six showed dysplasia, including one case of severe dysplasia. Five harboured hyperplastic lesions and in one woman no histological aberrations were found in the Fallopian tube. No hyperplastic, dysplastic or neoplastic lesions were detected in the Fallopian tubes of control subjects. In the cases studied, morphologically normal tubal epithelium contained a higher proportion of Ki67-expressing cells (p=0.005) and lower fractions of cells expressing p21 (p<0.0001) and p27 (p=0.006) than in the control group. Even higher fractions of proliferating cells were found in dysplastic areas (p=0.07) and accumulation of p53 was observed in the severely dysplastic lesion. Expression patterns of other proteins studied, including the hormone receptors, were similar in cases and controls. One subject, a germline BRCA1 mutation carrier, showed loss of the wild-type BRCA1 allele in the severely dysplastic lesion. In conclusion, the Fallopian tubes of women predisposed to developing ovarian cancer frequently harbour dysplastic changes, accompanied by changes in cell-cycle and apoptosis-related proteins, indicating an increased risk of developing tubal cancer.
| Original language | English |
|---|---|
| Pages (from-to) | 451-6 |
| Number of pages | 6 |
| Journal | Journal of Pathology |
| Volume | 195 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Nov 2001 |
Cite this
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Dysplastic changes in prophylactically removed Fallopian tubes of women predisposed to developing ovarian cancer. / Piek, J M; van Diest, P J; Zweemer, R P; Jansen, J W; Poort-Keesom, R J; Menko, F H; Gille, J J; Jongsma, A P; Pals, G; Kenemans, P; Verheijen, R H.
In: Journal of Pathology, Vol. 195, No. 4, 11.2001, p. 451-6.Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Dysplastic changes in prophylactically removed Fallopian tubes of women predisposed to developing ovarian cancer
AU - Piek, J M
AU - van Diest, P J
AU - Zweemer, R P
AU - Jansen, J W
AU - Poort-Keesom, R J
AU - Menko, F H
AU - Gille, J J
AU - Jongsma, A P
AU - Pals, G
AU - Kenemans, P
AU - Verheijen, R H
N1 - Copyright 2001 John Wiley & Sons, Ltd.
PY - 2001/11
Y1 - 2001/11
N2 - The aim of this study was to investigate the occurrence of (pre)neoplastic lesions in overtly normal Fallopian tubes from women predisposed to developing ovarian carcinoma. The presence of (pre)neoplastic lesions was scored in histological specimens from 12 women with a genetically determined predisposition for ovarian cancer, of whom seven tested positive for a germline BRCA1 mutation. A control group included 13 women. Immunohistochemistry was used to determine the expression of p21, p27, p53, cyclin A, cyclin D1, bcl-2, Ki67, HER-2/neu, and the oestrogen and progesterone receptors. Loss of heterozygosity (LOH) analysis on the BRCA1 locus was also assessed on dysplastic tissue by PCR studies. Of the 12 women with a predisposition for ovarian cancer, six showed dysplasia, including one case of severe dysplasia. Five harboured hyperplastic lesions and in one woman no histological aberrations were found in the Fallopian tube. No hyperplastic, dysplastic or neoplastic lesions were detected in the Fallopian tubes of control subjects. In the cases studied, morphologically normal tubal epithelium contained a higher proportion of Ki67-expressing cells (p=0.005) and lower fractions of cells expressing p21 (p<0.0001) and p27 (p=0.006) than in the control group. Even higher fractions of proliferating cells were found in dysplastic areas (p=0.07) and accumulation of p53 was observed in the severely dysplastic lesion. Expression patterns of other proteins studied, including the hormone receptors, were similar in cases and controls. One subject, a germline BRCA1 mutation carrier, showed loss of the wild-type BRCA1 allele in the severely dysplastic lesion. In conclusion, the Fallopian tubes of women predisposed to developing ovarian cancer frequently harbour dysplastic changes, accompanied by changes in cell-cycle and apoptosis-related proteins, indicating an increased risk of developing tubal cancer.
AB - The aim of this study was to investigate the occurrence of (pre)neoplastic lesions in overtly normal Fallopian tubes from women predisposed to developing ovarian carcinoma. The presence of (pre)neoplastic lesions was scored in histological specimens from 12 women with a genetically determined predisposition for ovarian cancer, of whom seven tested positive for a germline BRCA1 mutation. A control group included 13 women. Immunohistochemistry was used to determine the expression of p21, p27, p53, cyclin A, cyclin D1, bcl-2, Ki67, HER-2/neu, and the oestrogen and progesterone receptors. Loss of heterozygosity (LOH) analysis on the BRCA1 locus was also assessed on dysplastic tissue by PCR studies. Of the 12 women with a predisposition for ovarian cancer, six showed dysplasia, including one case of severe dysplasia. Five harboured hyperplastic lesions and in one woman no histological aberrations were found in the Fallopian tube. No hyperplastic, dysplastic or neoplastic lesions were detected in the Fallopian tubes of control subjects. In the cases studied, morphologically normal tubal epithelium contained a higher proportion of Ki67-expressing cells (p=0.005) and lower fractions of cells expressing p21 (p<0.0001) and p27 (p=0.006) than in the control group. Even higher fractions of proliferating cells were found in dysplastic areas (p=0.07) and accumulation of p53 was observed in the severely dysplastic lesion. Expression patterns of other proteins studied, including the hormone receptors, were similar in cases and controls. One subject, a germline BRCA1 mutation carrier, showed loss of the wild-type BRCA1 allele in the severely dysplastic lesion. In conclusion, the Fallopian tubes of women predisposed to developing ovarian cancer frequently harbour dysplastic changes, accompanied by changes in cell-cycle and apoptosis-related proteins, indicating an increased risk of developing tubal cancer.
KW - Adult
KW - Aged
KW - Case-Control Studies
KW - Cyclin A/metabolism
KW - Cyclin D1/metabolism
KW - Fallopian Tubes/pathology
KW - Female
KW - Genes, BRCA1/physiology
KW - Genes, bcl-2/physiology
KW - Humans
KW - Ki-67 Antigen/metabolism
KW - Loss of Heterozygosity
KW - Middle Aged
KW - Ovarian Neoplasms/genetics
KW - Polymerase Chain Reaction
KW - Precancerous Conditions/genetics
KW - Proliferating Cell Nuclear Antigen/metabolism
KW - Receptors, Estrogen/metabolism
KW - Receptors, Progesterone/metabolism
KW - Tumor Suppressor Protein p53/metabolism
KW - rho GTP-Binding Proteins/metabolism
U2 - 10.1002/path.1000
DO - 10.1002/path.1000
M3 - Article
VL - 195
SP - 451
EP - 456
JO - Journal of Pathology
JF - Journal of Pathology
SN - 0022-3417
IS - 4
ER -