Skip to main content
Erschienen in: Archives of Gynecology and Obstetrics 5/2014

01.05.2014 | Gynecologic Oncology

Ki-67 and p53 expression of the fallopian tube mucosa in breast cancer patients with hereditary risk

verfasst von: Alina Anton, Sarah Schott, Gisela Kaip, Michelle Rath, Jörg Heil, Sebastian Aulmann, Hans-Peter Sinn

Erschienen in: Archives of Gynecology and Obstetrics | Ausgabe 5/2014

Einloggen, um Zugang zu erhalten

Abstract

Purpose

The fallopian tube has been implicated as a site of origin of sporadic and BRCA1-related ovarian cancer. To investigate if Ki-67 or p53 is altered in BRCA1 mutation carriers, we have studied the expression of these markers in morphologically normal mucosa in the fallopian tube and fimbriae.

Methods

Prophylactic adnexectomy specimens from 24 patients (eight BRCA1 mutation carriers, eight non-mutation carriers, and eight with unknown BRCA1 status), were scored by automated image analysis for the amount of Ki-67 and wild-type p53 expression. All patients had a history of breast cancer and a family history of breast or ovarian cancer.

Results

In the fimbriae, a median of 0.42 % Ki-67 and 0.04 % p53-positive epithelial cells was present, compared to a median of 0.36 % for Ki-67 and 0.05 % for p53 in the fallopian tube. Ki-67 expression decreased significantly with age (r = −0.45, p = 0.028). In contrast, p53 expression was not age-dependent for the whole group of patients (r = 0.25, p = 0.25). Subgroup analysis revealed a difference for p53 expression of the BRCA1 mutation carriers with respect to age (median 0.039 vs. 0.082 % for age less or greater than 50.5 years). Consequently, the p53/Ki-67 ratio showed an age-dependent increase, which was accelerated in the BRCA1-positive patients.

Conclusions

Ki-67 and p53 expression varies in morphologically normal tubal epithelial cells depending on age and BRCA1 mutation status. This may reflect an altered and age-dependent DNA repair in BRCA1 mutation carriers and may be related to increased risk of ovarian cancer arising in the fallopian tube.
Literatur
1.
Zurück zum Zitat Waldmann A, Eisemann N, Katalinic A (2013) Epidemiology of malignant cervical, corpus uteri and ovarian tumours—current data and epidemiological trends (Epidemiologie der bösartigen tumoren der inneren weiblichen genitalorgane—aktuelle zahlen und epidemiologische trends). Geburtsh Frauenheilk 73(02):123–129. doi:10.1055/s-0032-1328266 PubMedCentralCrossRef Waldmann A, Eisemann N, Katalinic A (2013) Epidemiology of malignant cervical, corpus uteri and ovarian tumours—current data and epidemiological trends (Epidemiologie der bösartigen tumoren der inneren weiblichen genitalorgane—aktuelle zahlen und epidemiologische trends). Geburtsh Frauenheilk 73(02):123–129. doi:10.​1055/​s-0032-1328266 PubMedCentralCrossRef
2.
Zurück zum Zitat Risch HA, Howe GR (1995) Pelvic inflammatory disease and the risk of epithelial ovarian cancer. Cancer Epidemiol Biomarkers Prev 4(5):447–451PubMed Risch HA, Howe GR (1995) Pelvic inflammatory disease and the risk of epithelial ovarian cancer. Cancer Epidemiol Biomarkers Prev 4(5):447–451PubMed
3.
Zurück zum Zitat Pearce CL, Templeman C, Rossing MA, Lee A, Near AM, Webb PM, Nagle CM, Doherty JA, Cushing-Haugen KL, Wicklund KG, Chang-Claude J, Hein R, Lurie G, Wilkens LR, Carney ME, Goodman MT, Moysich K, Kjaer SK, Hogdall E, Jensen A, Goode EL, Fridley BL, Larson MC, Schildkraut JM, Palmieri RT, Cramer DW, Terry KL, Vitonis AF, Titus LJ, Ziogas A, Brewster W, Anton-Culver H, Gentry-Maharaj A, Ramus SJ, Anderson AR, Brueggmann D, Fasching PA, Gayther SA, Huntsman DG, Menon U, Ness RB, Pike MC, Risch H, Wu AH, Berchuck A (2012) Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies. Lancet Oncol 13(4):385–394. doi:10.1016/S1470-2045(11)70404-1 PubMedCentralPubMedCrossRef Pearce CL, Templeman C, Rossing MA, Lee A, Near AM, Webb PM, Nagle CM, Doherty JA, Cushing-Haugen KL, Wicklund KG, Chang-Claude J, Hein R, Lurie G, Wilkens LR, Carney ME, Goodman MT, Moysich K, Kjaer SK, Hogdall E, Jensen A, Goode EL, Fridley BL, Larson MC, Schildkraut JM, Palmieri RT, Cramer DW, Terry KL, Vitonis AF, Titus LJ, Ziogas A, Brewster W, Anton-Culver H, Gentry-Maharaj A, Ramus SJ, Anderson AR, Brueggmann D, Fasching PA, Gayther SA, Huntsman DG, Menon U, Ness RB, Pike MC, Risch H, Wu AH, Berchuck A (2012) Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies. Lancet Oncol 13(4):385–394. doi:10.​1016/​S1470-2045(11)70404-1 PubMedCentralPubMedCrossRef
4.
Zurück zum Zitat Ford D, Easton DF, Peto J (1995) Estimates of the gene frequency of BRCA1 and its contribution to breast and ovarian cancer incidence. Am J Hum Genet 57(6):1457–1462PubMedCentralPubMed Ford D, Easton DF, Peto J (1995) Estimates of the gene frequency of BRCA1 and its contribution to breast and ovarian cancer incidence. Am J Hum Genet 57(6):1457–1462PubMedCentralPubMed
5.
Zurück zum Zitat Gayther SA, Mangion J, Russell P, Seal S, Barfoot R, Ponder BA, Stratton MR, Easton D (1997) Variation of risks of breast and ovarian cancer associated with different germline mutations of the BRCA2 gene. Nat Genet 15(1):103–105. doi:10.1038/ng0197-103 PubMedCrossRef Gayther SA, Mangion J, Russell P, Seal S, Barfoot R, Ponder BA, Stratton MR, Easton D (1997) Variation of risks of breast and ovarian cancer associated with different germline mutations of the BRCA2 gene. Nat Genet 15(1):103–105. doi:10.​1038/​ng0197-103 PubMedCrossRef
6.
Zurück zum Zitat Brose MS, Rebbeck TR, Calzone KA, Stopfer JE, Nathanson KL, Weber BL (2002) Cancer risk estimates for BRCA1 mutation carriers identified in a risk evaluation program. J Natl Cancer Inst 94(18):1365–1372PubMedCrossRef Brose MS, Rebbeck TR, Calzone KA, Stopfer JE, Nathanson KL, Weber BL (2002) Cancer risk estimates for BRCA1 mutation carriers identified in a risk evaluation program. J Natl Cancer Inst 94(18):1365–1372PubMedCrossRef
7.
Zurück zum Zitat Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P, Bishop DT, Weber B, Lenoir G, Chang-Claude J, Sobol H, Teare MD, Struewing J, Arason A, Scherneck S, Peto J, Rebbeck TR, Tonin P, Neuhausen S, Barkardottir R, Eyfjord J, Lynch H, Ponder BA, Gayther SA, Zelada-Hedman M et al (1998) Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The breast cancer linkage consortium. Am J Hum Genet 62(3):676–689 pii: S0002-9297(07)63848-8PubMedCentralPubMedCrossRef Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P, Bishop DT, Weber B, Lenoir G, Chang-Claude J, Sobol H, Teare MD, Struewing J, Arason A, Scherneck S, Peto J, Rebbeck TR, Tonin P, Neuhausen S, Barkardottir R, Eyfjord J, Lynch H, Ponder BA, Gayther SA, Zelada-Hedman M et al (1998) Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The breast cancer linkage consortium. Am J Hum Genet 62(3):676–689 pii: S0002-9297(07)63848-8PubMedCentralPubMedCrossRef
9.
Zurück zum Zitat Zweemer RP, van Diest PJ, Verheijen RH, Ryan A, Gille JJ, Sijmons RH, Jacobs IJ, Menko FH, Kenemans P (2000) Molecular evidence linking primary cancer of the fallopian tube to BRCA1 germline mutations. Gynecol Oncol 76(1):45–50. doi:10.1006/gyno.1999.5623 PubMedCrossRef Zweemer RP, van Diest PJ, Verheijen RH, Ryan A, Gille JJ, Sijmons RH, Jacobs IJ, Menko FH, Kenemans P (2000) Molecular evidence linking primary cancer of the fallopian tube to BRCA1 germline mutations. Gynecol Oncol 76(1):45–50. doi:10.​1006/​gyno.​1999.​5623 PubMedCrossRef
10.
Zurück zum Zitat Paley PJ, Swisher EM, Garcia RL, Agoff SN, Greer BE, Peters KL, Goff BA (2001) Occult cancer of the fallopian tube in BRCA-1 germline mutation carriers at prophylactic oophorectomy: a case for recommending hysterectomy at surgical prophylaxis. Gynecol Oncol 80(2):176–180. doi:10.1006/gyno.2000.6071 PubMedCrossRef Paley PJ, Swisher EM, Garcia RL, Agoff SN, Greer BE, Peters KL, Goff BA (2001) Occult cancer of the fallopian tube in BRCA-1 germline mutation carriers at prophylactic oophorectomy: a case for recommending hysterectomy at surgical prophylaxis. Gynecol Oncol 80(2):176–180. doi:10.​1006/​gyno.​2000.​6071 PubMedCrossRef
11.
Zurück zum Zitat 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. J Pathol 195(4):451–456. doi:10.1002/path.1000 PubMedCrossRef 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. J Pathol 195(4):451–456. doi:10.​1002/​path.​1000 PubMedCrossRef
13.
Zurück zum Zitat Kauff ND, Satagopan JM, Robson ME, Scheuer L, Hensley M, Hudis CA, Ellis NA, Boyd J, Borgen PI, Barakat RR, Norton L, Castiel M, Nafa K, Offit K (2002) Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 346(21):1609–1615. doi:10.1056/NEJMoa020119 PubMedCrossRef Kauff ND, Satagopan JM, Robson ME, Scheuer L, Hensley M, Hudis CA, Ellis NA, Boyd J, Borgen PI, Barakat RR, Norton L, Castiel M, Nafa K, Offit K (2002) Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 346(21):1609–1615. doi:10.​1056/​NEJMoa020119 PubMedCrossRef
14.
Zurück zum Zitat Rebbeck TR (2002) Prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers. Eur J Cancer 38(Suppl 6):S15–S17 (pii: S0959804902002691)PubMedCrossRef Rebbeck TR (2002) Prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers. Eur J Cancer 38(Suppl 6):S15–S17 (pii: S0959804902002691)PubMedCrossRef
15.
Zurück zum Zitat Rutter JL, Wacholder S, Chetrit A, Lubin F, Menczer J, Ebbers S, Tucker MA, Struewing JP, Hartge P (2003) Gynecologic surgeries and risk of ovarian cancer in women with BRCA1 and BRCA2 Ashkenazi founder mutations: an Israeli population-based case-control study. J Natl Cancer Inst 95(14):1072–1078PubMedCrossRef Rutter JL, Wacholder S, Chetrit A, Lubin F, Menczer J, Ebbers S, Tucker MA, Struewing JP, Hartge P (2003) Gynecologic surgeries and risk of ovarian cancer in women with BRCA1 and BRCA2 Ashkenazi founder mutations: an Israeli population-based case-control study. J Natl Cancer Inst 95(14):1072–1078PubMedCrossRef
18.
Zurück zum Zitat Powell CB, Kenley E, Chen LM, Crawford B, McLennan J, Zaloudek C, Komaromy M, Beattie M, Ziegler J (2005) Risk-reducing salpingo-oophorectomy in BRCA mutation carriers: role of serial sectioning in the detection of occult malignancy. J Clin Oncol 23(1):127–132. doi:10.1200/JCO.2005.04.109 PubMedCrossRef Powell CB, Kenley E, Chen LM, Crawford B, McLennan J, Zaloudek C, Komaromy M, Beattie M, Ziegler J (2005) Risk-reducing salpingo-oophorectomy in BRCA mutation carriers: role of serial sectioning in the detection of occult malignancy. J Clin Oncol 23(1):127–132. doi:10.​1200/​JCO.​2005.​04.​109 PubMedCrossRef
19.
Zurück zum Zitat Folkins AK, Jarboe EA, Saleemuddin A, Lee Y, Callahan MJ, Drapkin R, Garber JE, Muto MG, Tworoger S, Crum CP (2008) A candidate precursor to pelvic serous cancer (p53 signature) and its prevalence in ovaries and fallopian tubes from women with BRCA mutations. Gynecol Oncol 109(2):168–173. doi:10.1016/j.ygyno.2008.01.012 PubMedCentralPubMedCrossRef Folkins AK, Jarboe EA, Saleemuddin A, Lee Y, Callahan MJ, Drapkin R, Garber JE, Muto MG, Tworoger S, Crum CP (2008) A candidate precursor to pelvic serous cancer (p53 signature) and its prevalence in ovaries and fallopian tubes from women with BRCA mutations. Gynecol Oncol 109(2):168–173. doi:10.​1016/​j.​ygyno.​2008.​01.​012 PubMedCentralPubMedCrossRef
21.
Zurück zum Zitat Medeiros F, Muto MG, Lee Y, Elvin JA, Callahan MJ, Feltmate C, Garber JE, Cramer DW, Crum CP (2006) The tubal fimbria is a preferred site for early adenocarcinoma in women with familial ovarian cancer syndrome. Am J Surg Pathol 30(2):230–236 (pii: 00000478-200602000-00012)PubMedCrossRef Medeiros F, Muto MG, Lee Y, Elvin JA, Callahan MJ, Feltmate C, Garber JE, Cramer DW, Crum CP (2006) The tubal fimbria is a preferred site for early adenocarcinoma in women with familial ovarian cancer syndrome. Am J Surg Pathol 30(2):230–236 (pii: 00000478-200602000-00012)PubMedCrossRef
22.
Zurück zum Zitat Colgan TJ, Murphy J, Cole DE, Narod S, Rosen B (2001) Occult carcinoma in prophylactic oophorectomy specimens: prevalence and association with BRCA germline mutation status. Am J Surg Pathol 25(10):1283–1289PubMedCrossRef Colgan TJ, Murphy J, Cole DE, Narod S, Rosen B (2001) Occult carcinoma in prophylactic oophorectomy specimens: prevalence and association with BRCA germline mutation status. Am J Surg Pathol 25(10):1283–1289PubMedCrossRef
24.
Zurück zum Zitat Singer G, Stohr R, Cope L, Dehari R, Hartmann A, Cao DF, Wang TL, Kurman RJ, Shih Ie M (2005) Patterns of p53 mutations separate ovarian serous borderline tumors and low- and high-grade carcinomas and provide support for a new model of ovarian carcinogenesis: a mutational analysis with immunohistochemical correlation. Am J Surg Pathol 29(2):218–224 (pii: 00000478-200502000-00009)PubMedCrossRef Singer G, Stohr R, Cope L, Dehari R, Hartmann A, Cao DF, Wang TL, Kurman RJ, Shih Ie M (2005) Patterns of p53 mutations separate ovarian serous borderline tumors and low- and high-grade carcinomas and provide support for a new model of ovarian carcinogenesis: a mutational analysis with immunohistochemical correlation. Am J Surg Pathol 29(2):218–224 (pii: 00000478-200502000-00009)PubMedCrossRef
26.
Zurück zum Zitat R Development Core Team (2011) R: a language and environment for statistical computing. Vienna R Development Core Team (2011) R: a language and environment for statistical computing. Vienna
27.
Zurück zum Zitat Kindelberger DW, Lee Y, Miron A, Hirsch MS, Feltmate C, Medeiros F, Callahan MJ, Garner EO, Gordon RW, Birch C, Berkowitz RS, Muto MG, Crum CP (2007) Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: evidence for a causal relationship. Am J Surg Pathol 31(2):161–169. doi:10.1097/01.pas.0000213335.40358.47 PubMedCrossRef Kindelberger DW, Lee Y, Miron A, Hirsch MS, Feltmate C, Medeiros F, Callahan MJ, Garner EO, Gordon RW, Birch C, Berkowitz RS, Muto MG, Crum CP (2007) Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: evidence for a causal relationship. Am J Surg Pathol 31(2):161–169. doi:10.​1097/​01.​pas.​0000213335.​40358.​47 PubMedCrossRef
Metadaten
Titel
Ki-67 and p53 expression of the fallopian tube mucosa in breast cancer patients with hereditary risk
verfasst von
Alina Anton
Sarah Schott
Gisela Kaip
Michelle Rath
Jörg Heil
Sebastian Aulmann
Hans-Peter Sinn
Publikationsdatum
01.05.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Archives of Gynecology and Obstetrics / Ausgabe 5/2014
Print ISSN: 0932-0067
Elektronische ISSN: 1432-0711
DOI
https://doi.org/10.1007/s00404-013-3062-y

Weitere Artikel der Ausgabe 5/2014

Archives of Gynecology and Obstetrics 5/2014 Zur Ausgabe

Ambulantisierung: Erste Erfahrungen mit dem Hybrid-DRG

02.05.2024 DCK 2024 Kongressbericht

Die Hybrid-DRG-Verordnung soll dazu führen, dass mehr chirurgische Eingriffe ambulant durchgeführt werden, wie es in anderen Ländern schon länger üblich ist. Die gleiche Vergütung im ambulanten und stationären Sektor hatten Niedergelassene schon lange gefordert. Aber die Umsetzung bereitet ihnen doch Kopfzerbrechen.

Sind Frauen die fähigeren Ärzte?

30.04.2024 Gendermedizin Nachrichten

Patienten, die von Ärztinnen behandelt werden, dürfen offenbar auf bessere Therapieergebnisse hoffen als Patienten von Ärzten. Besonders gilt das offenbar für weibliche Kranke, wie eine Studie zeigt.

Harninkontinenz: Netz-Op. erfordert über lange Zeit intensive Nachsorge

30.04.2024 Harninkontinenz Nachrichten

Frauen mit Belastungsinkontinenz oder Organprolaps sind nach einer Netz-Operation keineswegs beschwerdefrei. Vielmehr scheint die Krankheitslast weiterhin hoch zu sein, sogar höher als von harninkontinenten Frauen, die sich nicht haben operieren lassen.

Welche Übungen helfen gegen Diastase recti abdominis?

30.04.2024 Schwangerenvorsorge Nachrichten

Die Autorinnen und Autoren einer aktuellen Studie aus Griechenland sind sich einig, dass Bewegungstherapie, einschließlich Übungen zur Stärkung der Bauchmuskulatur und zur Stabilisierung des Rumpfes, eine Diastase recti abdominis postpartum wirksam reduzieren kann. Doch vieles ist noch nicht eindeutig belegt.

Update Gynäkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.