Dysplastic changes in prophylactically removed Fallopian tubes of women predisposed to developing ovarian cancer

J M Piek, P J van Diest, R P Zweemer, J W Jansen, R J Poort-Keesom, F H Menko, J J Gille, A P Jongsma, G Pals, P Kenemans, R H Verheijen

Research output: Contribution to journalArticleAcademicpeer-review

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 languageEnglish
Pages (from-to)451-6
Number of pages6
JournalJournal of Pathology
Volume195
Issue number4
DOIs
Publication statusPublished - Nov 2001

Cite this

Piek, J. M., van Diest, P. J., Zweemer, R. P., Jansen, J. W., Poort-Keesom, R. J., Menko, F. H., ... Verheijen, R. H. (2001). Dysplastic changes in prophylactically removed Fallopian tubes of women predisposed to developing ovarian cancer. Journal of Pathology, 195(4), 451-6. https://doi.org/10.1002/path.1000
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. / Dysplastic changes in prophylactically removed Fallopian tubes of women predisposed to developing ovarian cancer. In: Journal of Pathology. 2001 ; Vol. 195, No. 4. pp. 451-6.
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title = "Dysplastic changes in prophylactically removed Fallopian tubes of women predisposed to developing ovarian cancer",
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.",
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author = "Piek, {J M} and {van Diest}, {P J} and Zweemer, {R P} and Jansen, {J W} and Poort-Keesom, {R J} and Menko, {F H} and Gille, {J J} and Jongsma, {A P} and G Pals and P Kenemans and Verheijen, {R H}",
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Piek, JM, van Diest, PJ, Zweemer, RP, Jansen, JW, Poort-Keesom, RJ, Menko, FH, Gille, JJ, Jongsma, AP, Pals, G, Kenemans, P & Verheijen, RH 2001, 'Dysplastic changes in prophylactically removed Fallopian tubes of women predisposed to developing ovarian cancer' Journal of Pathology, vol. 195, no. 4, pp. 451-6. https://doi.org/10.1002/path.1000

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 journalArticleAcademicpeer-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 -