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Correlation between protein and gene expression of HER-2 and topoisomerase 2a in infiltrative ductal breast carcinoma

Korelacija između proteinske i genske ekspresije HER-2 i topoizomeraze 2a kod infiltrativnog duktalnog karcinoma dojke

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2013
1091.pdf (8.216Mb)
Authors
Mitrović, Olivera S.
Contributors
Koko, Vesna
Čokić, Vladan
Budeč, Mirela
Markelić, Milica
Doctoral thesis (Published version)
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Abstract
Introduction: Breast cancer is a heterogeneous disease and the most common malignancy in women with increasing incidence in recent years. According to immunohistochemical expression of estrogen receptor (ER-R), progesterone receptor (PR-R) and HER-2 four different molecular subtypes of breast cancer were identified: luminal A (ER-R+ and / or PR-R+, HER-2-), luminal B (ER-R+ and / or PR-R+, HER- 2+), HER-2 positive (ER-R- and / or PR-R-, HER-2+) and triple negative (ER-R- and / or PR-R-, HER-2-) breast cancer subtypes. HER-2 and TOP2A genes are amplified in 20– 30 % of breast cancers. Amplification of HER-2 and TOP2A genes are associated with a poor prognosis and predictive response to treatment by Herceptin and anthracycline. Co-amplification of HER-2 and TOP2A has been seen in approximately 12–38 % of patients with breast cancers. A few retrospective studies have reported that TOP2A gene amplification occurs almost exclusively in conjunction with HER-2 gene amplification. Aim: The aim... of our study is to investigate HER-2 and TOP2A gene aberrations and their correlation with apoptotic and proliferative indexes, Bcl-2, p53, ER-R, PR-R, HER-2, TOP2A, BRCA1, clinicopathological parameters and overall survival in four molecular subtypes of breast cancer. Material and methods: Sixty paraffin-embedded breast cancer tissue samples were studied immunohistochemically for the expression of ER-R, PR-R, HER-2, p53, Bcl-2, ssDNA, Ki67, BRCA1, TOP2A and FISH for HER-2 and TOP2A gene aberrations. HER-2 and TOP2A gene copy number were analyzed by HER-2 FISH pharmDxTM kit and TOP2A FISH pharmDxTM kit (DakoCytomation), respectively. Results: Clinicopathological parameters - The ages of patients ranged from 38 to 87 years (64.79 ± 21). The tumor size ranged between 0.4 and 5.5 cm, and the histological grades were G1, G2 and G3 in 6 (10 %), 25 (41.7 %), and 17 (28.3 %) patients, respectively. In 26 patients (43.4 %) lymph node status was negative; while in 22 patients (36.6 %) was detected positive lymph node status...

Uvod: Karcinom dojke predstavlja jako heterogeno oboljenje kao i jedno od najzastupljenijih malignih bolesti u opštoj ženskoj populaciji. Na osnovu prisustva i nivoa ekspresije ER-R, PR-R i HER-2 receptora ostvarena je podela na četiri molekularna tipa karcinoma dojke: luminalni A (ER-R+ i / ili PR-R+, HER-2-), luminalni B (ER-R+ i / ili PR-R+, HER-2+), HER-2 pozitivni (ER-R- i / ili PR-R-, HER-2+) i trostruko negativni (ER-R- i / ili PR-R-, HER-2-) tip karcinoma dojke. U oko 20 do 30% karcinoma dojke javlja se amplifikacija HER-2 i TOP2A gena. Amplifikacija HER-2 i TOP2A gena je povezana sa lošijim ishodom bolesti, agresivnijim tokom i dobrim odgovorom pacijentkinja na terapiju Herceptinom i antraciklinima. Koamplifikacija HER-2 i TOP2A gena je prisutna u 12 do 38% karcinoma dojke. Na osnovu rezultata nekoliko studija postavljena je hipoteza po kojoj se amplifikacija TOP2A gena javlja isključivo sa amplifikacijom HER-2 gena, mada postoje i drugačija, suprotna mišljenja. Cilj: Cilj naš...e studije bio je da se odrede genski statusi HER-2 i TOP2A kao i njihova korelacija sa apoptotskim i proliferativnim indeksom, nivoom ekspresije ER-R, PR-R i HER-2 receptora, TOP2A, BRCA1, Bcl-2 i p53 proteina, osnovnim kliničko-patološkim parametrima kod tumora dojke 60 pacijentkinja podeljenih u četiri molekularna tipa. Materijal i metode: Šezdeset tkivnih uzoraka karcinoma dojke ispitivano je imunohistohemijskom metodom na prisustvo i stepen ekspresije ER-R, PR-R, HER-2, p53, Bcl-2, TOP2A, BRCA1, ssDNA, Ki67, kao i FISH metodom na stepen genske modifikacije HER-2 i TOP2A. Stepen modifikacije HER-2 i TOP2A gena analiziran je primenom HER-2 FISH pharmDxTM kit i TOP2A FISH pharmDxTM kit (DakoCytomation). Rezultati: Kliničko-patološki podaci - Starost ispitanica se kretala u rasponu izmeñu 38 i 87 godina (64.79 ± 21). Veličina tumora se kretala u opsegu izmeñu 0.4 i 5.5 cm, dok je histološki gradus G1 bio zastupljen kod 6 (10%) karcinoma, histološki gradus G2 kod 25 (41.7%) i histološki gradus G3 kod 17 (28.3%) karcinoma dojke...

Keywords:
molecular subtypes of breast cancer / HER-2 and TOP2A gene aberrations / ER-R / PR-R / HER-2 / p53 / Bcl-2 / TOP2A / BRCA1 / Ki67 and ssDNA expression / molekularni tipovi karcinoma dojke / HER-2 i TOP2A genske aberacije / ER-R / PR-R / HER-2 / TOP2A / BRCA1 / p53 / Bcl-2 / Ki67 i ssDNA imunohistohemijska ekspresija
Source:
2013
Publisher:
  • Univerzitet u Beogradu, Biološki fakultet
Funding / projects:
  • The pathogenetic mechanism in hematological malignancies (RS-175053)
[ Google Scholar ]
Handle
https://hdl.handle.net/21.15107/rcub_nardus_2125
URI
http://nardus.mpn.gov.rs/handle/123456789/2125
http://eteze.bg.ac.rs/application/showtheses?thesesId=883
https://fedorabg.bg.ac.rs/fedora/get/o:7287/bdef:Content/download
http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=44859407
http://rimi.imi.bg.ac.rs/handle/123456789/1094
Collections
  • Doktorati / Doctoral thesis
Institution/Community
Institut za medicinska istraživanja
TY  - THES
AU  - Mitrović, Olivera S.
PY  - 2013
UR  - http://nardus.mpn.gov.rs/handle/123456789/2125
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=883
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:7287/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=44859407
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1094
AB  - Introduction: Breast cancer is a heterogeneous disease and the most common malignancy in women with increasing incidence in recent years. According to immunohistochemical expression of estrogen receptor (ER-R), progesterone receptor (PR-R) and HER-2 four different molecular subtypes of breast cancer were identified: luminal A (ER-R+ and / or PR-R+, HER-2-), luminal B (ER-R+ and / or PR-R+, HER- 2+), HER-2 positive (ER-R- and / or PR-R-, HER-2+) and triple negative (ER-R- and / or PR-R-, HER-2-) breast cancer subtypes. HER-2 and TOP2A genes are amplified in 20– 30 % of breast cancers. Amplification of HER-2 and TOP2A genes are associated with a poor prognosis and predictive response to treatment by Herceptin and anthracycline. Co-amplification of HER-2 and TOP2A has been seen in approximately 12–38 % of patients with breast cancers. A few retrospective studies have reported that TOP2A gene amplification occurs almost exclusively in conjunction with HER-2 gene amplification. Aim: The aim of our study is to investigate HER-2 and TOP2A gene aberrations and their correlation with apoptotic and proliferative indexes, Bcl-2, p53, ER-R, PR-R, HER-2, TOP2A, BRCA1, clinicopathological parameters and overall survival in four molecular subtypes of breast cancer. Material and methods: Sixty paraffin-embedded breast cancer tissue samples were studied immunohistochemically for the expression of ER-R, PR-R, HER-2, p53, Bcl-2, ssDNA, Ki67, BRCA1, TOP2A and FISH for HER-2 and TOP2A gene aberrations. HER-2 and TOP2A gene copy number were analyzed by HER-2 FISH pharmDxTM kit and TOP2A FISH pharmDxTM kit (DakoCytomation), respectively. Results: Clinicopathological parameters - The ages of patients ranged from 38 to 87 years (64.79 ± 21). The tumor size ranged between 0.4 and 5.5 cm, and the histological grades were G1, G2 and G3 in 6 (10 %), 25 (41.7 %), and 17 (28.3 %) patients, respectively. In 26 patients (43.4 %) lymph node status was negative; while in 22 patients (36.6 %) was detected positive lymph node status...
AB  - Uvod: Karcinom dojke predstavlja jako heterogeno oboljenje kao i jedno od najzastupljenijih malignih bolesti u opštoj ženskoj populaciji. Na osnovu prisustva i nivoa ekspresije ER-R, PR-R i HER-2 receptora ostvarena je podela na četiri molekularna tipa karcinoma dojke: luminalni A (ER-R+ i / ili PR-R+, HER-2-), luminalni B (ER-R+ i / ili PR-R+, HER-2+), HER-2 pozitivni (ER-R- i / ili PR-R-, HER-2+) i trostruko negativni (ER-R- i / ili PR-R-, HER-2-) tip karcinoma dojke. U oko 20 do 30% karcinoma dojke javlja se amplifikacija HER-2 i TOP2A gena. Amplifikacija HER-2 i TOP2A gena je povezana sa lošijim ishodom bolesti, agresivnijim tokom i dobrim odgovorom pacijentkinja na terapiju Herceptinom i antraciklinima. Koamplifikacija HER-2 i TOP2A gena je prisutna u 12 do 38% karcinoma dojke. Na osnovu rezultata nekoliko studija postavljena je hipoteza po kojoj se amplifikacija TOP2A gena javlja isključivo sa amplifikacijom HER-2 gena, mada postoje i drugačija, suprotna mišljenja. Cilj: Cilj naše studije bio je da se odrede genski statusi HER-2 i TOP2A kao i njihova korelacija sa apoptotskim i proliferativnim indeksom, nivoom ekspresije ER-R, PR-R i HER-2 receptora, TOP2A, BRCA1, Bcl-2 i p53 proteina, osnovnim kliničko-patološkim parametrima kod tumora dojke 60 pacijentkinja podeljenih u četiri molekularna tipa. Materijal i metode: Šezdeset tkivnih uzoraka karcinoma dojke ispitivano je imunohistohemijskom metodom na prisustvo i stepen ekspresije ER-R, PR-R, HER-2, p53, Bcl-2, TOP2A, BRCA1, ssDNA, Ki67, kao i FISH metodom na stepen genske modifikacije HER-2 i TOP2A. Stepen modifikacije HER-2 i TOP2A gena analiziran je primenom HER-2 FISH pharmDxTM kit i TOP2A FISH pharmDxTM kit (DakoCytomation). Rezultati: Kliničko-patološki podaci - Starost ispitanica se kretala u rasponu izmeñu 38 i 87 godina (64.79 ± 21). Veličina tumora se kretala u opsegu izmeñu 0.4 i 5.5 cm, dok je histološki gradus G1 bio zastupljen kod 6 (10%) karcinoma, histološki gradus G2 kod 25 (41.7%) i histološki gradus G3 kod 17 (28.3%) karcinoma dojke...
PB  - Univerzitet u Beogradu, Biološki fakultet
T1  - Correlation between protein and gene expression of HER-2 and topoisomerase 2a in infiltrative ductal breast carcinoma
T1  - Korelacija između proteinske i genske ekspresije HER-2 i topoizomeraze 2a kod infiltrativnog duktalnog karcinoma dojke
UR  - t-382
UR  - https://hdl.handle.net/21.15107/rcub_nardus_2125
ER  - 
@phdthesis{
author = "Mitrović, Olivera S.",
year = "2013",
abstract = "Introduction: Breast cancer is a heterogeneous disease and the most common malignancy in women with increasing incidence in recent years. According to immunohistochemical expression of estrogen receptor (ER-R), progesterone receptor (PR-R) and HER-2 four different molecular subtypes of breast cancer were identified: luminal A (ER-R+ and / or PR-R+, HER-2-), luminal B (ER-R+ and / or PR-R+, HER- 2+), HER-2 positive (ER-R- and / or PR-R-, HER-2+) and triple negative (ER-R- and / or PR-R-, HER-2-) breast cancer subtypes. HER-2 and TOP2A genes are amplified in 20– 30 % of breast cancers. Amplification of HER-2 and TOP2A genes are associated with a poor prognosis and predictive response to treatment by Herceptin and anthracycline. Co-amplification of HER-2 and TOP2A has been seen in approximately 12–38 % of patients with breast cancers. A few retrospective studies have reported that TOP2A gene amplification occurs almost exclusively in conjunction with HER-2 gene amplification. Aim: The aim of our study is to investigate HER-2 and TOP2A gene aberrations and their correlation with apoptotic and proliferative indexes, Bcl-2, p53, ER-R, PR-R, HER-2, TOP2A, BRCA1, clinicopathological parameters and overall survival in four molecular subtypes of breast cancer. Material and methods: Sixty paraffin-embedded breast cancer tissue samples were studied immunohistochemically for the expression of ER-R, PR-R, HER-2, p53, Bcl-2, ssDNA, Ki67, BRCA1, TOP2A and FISH for HER-2 and TOP2A gene aberrations. HER-2 and TOP2A gene copy number were analyzed by HER-2 FISH pharmDxTM kit and TOP2A FISH pharmDxTM kit (DakoCytomation), respectively. Results: Clinicopathological parameters - The ages of patients ranged from 38 to 87 years (64.79 ± 21). The tumor size ranged between 0.4 and 5.5 cm, and the histological grades were G1, G2 and G3 in 6 (10 %), 25 (41.7 %), and 17 (28.3 %) patients, respectively. In 26 patients (43.4 %) lymph node status was negative; while in 22 patients (36.6 %) was detected positive lymph node status..., Uvod: Karcinom dojke predstavlja jako heterogeno oboljenje kao i jedno od najzastupljenijih malignih bolesti u opštoj ženskoj populaciji. Na osnovu prisustva i nivoa ekspresije ER-R, PR-R i HER-2 receptora ostvarena je podela na četiri molekularna tipa karcinoma dojke: luminalni A (ER-R+ i / ili PR-R+, HER-2-), luminalni B (ER-R+ i / ili PR-R+, HER-2+), HER-2 pozitivni (ER-R- i / ili PR-R-, HER-2+) i trostruko negativni (ER-R- i / ili PR-R-, HER-2-) tip karcinoma dojke. U oko 20 do 30% karcinoma dojke javlja se amplifikacija HER-2 i TOP2A gena. Amplifikacija HER-2 i TOP2A gena je povezana sa lošijim ishodom bolesti, agresivnijim tokom i dobrim odgovorom pacijentkinja na terapiju Herceptinom i antraciklinima. Koamplifikacija HER-2 i TOP2A gena je prisutna u 12 do 38% karcinoma dojke. Na osnovu rezultata nekoliko studija postavljena je hipoteza po kojoj se amplifikacija TOP2A gena javlja isključivo sa amplifikacijom HER-2 gena, mada postoje i drugačija, suprotna mišljenja. Cilj: Cilj naše studije bio je da se odrede genski statusi HER-2 i TOP2A kao i njihova korelacija sa apoptotskim i proliferativnim indeksom, nivoom ekspresije ER-R, PR-R i HER-2 receptora, TOP2A, BRCA1, Bcl-2 i p53 proteina, osnovnim kliničko-patološkim parametrima kod tumora dojke 60 pacijentkinja podeljenih u četiri molekularna tipa. Materijal i metode: Šezdeset tkivnih uzoraka karcinoma dojke ispitivano je imunohistohemijskom metodom na prisustvo i stepen ekspresije ER-R, PR-R, HER-2, p53, Bcl-2, TOP2A, BRCA1, ssDNA, Ki67, kao i FISH metodom na stepen genske modifikacije HER-2 i TOP2A. Stepen modifikacije HER-2 i TOP2A gena analiziran je primenom HER-2 FISH pharmDxTM kit i TOP2A FISH pharmDxTM kit (DakoCytomation). Rezultati: Kliničko-patološki podaci - Starost ispitanica se kretala u rasponu izmeñu 38 i 87 godina (64.79 ± 21). Veličina tumora se kretala u opsegu izmeñu 0.4 i 5.5 cm, dok je histološki gradus G1 bio zastupljen kod 6 (10%) karcinoma, histološki gradus G2 kod 25 (41.7%) i histološki gradus G3 kod 17 (28.3%) karcinoma dojke...",
publisher = "Univerzitet u Beogradu, Biološki fakultet",
title = "Correlation between protein and gene expression of HER-2 and topoisomerase 2a in infiltrative ductal breast carcinoma, Korelacija između proteinske i genske ekspresije HER-2 i topoizomeraze 2a kod infiltrativnog duktalnog karcinoma dojke",
url = "t-382, https://hdl.handle.net/21.15107/rcub_nardus_2125"
}
Mitrović, O. S.. (2013). Correlation between protein and gene expression of HER-2 and topoisomerase 2a in infiltrative ductal breast carcinoma. 
Univerzitet u Beogradu, Biološki fakultet..
t-382
Mitrović OS. Correlation between protein and gene expression of HER-2 and topoisomerase 2a in infiltrative ductal breast carcinoma. 2013;.
t-382 .
Mitrović, Olivera S., "Correlation between protein and gene expression of HER-2 and topoisomerase 2a in infiltrative ductal breast carcinoma" (2013),
t-382 .

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