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Familial breast can...
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Aaltonen, Kirsimari
(författare)
Familial breast cancers without mutations in BRCA1 or BRCA2 have low cyclin E and high cyclin D1 in contrast to cancers in BRCA mutation carriers
- Artikel/kapitelEngelska2008
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LIBRIS-ID:oai:DiVA.org:uu-105396
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-105396URI
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https://doi.org/10.1158/1078-0432.CCR-07-4100DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
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PURPOSE: We analyzed the expression of critical cell cycle regulators cyclin E and cyclin D1 in familial breast cancer, focusing on BRCA mutation-negative tumors. Cyclin E expression in tumors of BRCA1 or BRCA2 carriers is higher, and cyclin D1 expression lower, than in sporadic tumors. In familial non-BRCA1/2 tumors, cyclin E and cyclin D1 expression has not been studied. EXPERIMENTAL DESIGN: Cyclin E and cyclin D1 immunohistochemical expression was studied in tissue microarrays consisting of 53 BRCA1, 58 BRCA2, 798 familial non-BRCA1/2, and 439 sporadic breast tumors. RESULTS: In univariate analysis, BRCA1 tumors had significantly more frequently high cyclin E (88%) and low cyclin D1 (84%) expression than sporadic (54% and 49%, respectively) or familial non-BRCA1/2 (38% and 45%, respectively) tumors. BRCA2 tumors had significantly more frequently low cyclin D1 expression (68%) than sporadic or familial non-BRCA1/2 tumors and significantly more frequently high cyclin E expression than familial non-BRCA1/2 tumors. In a logistic regression model, cyclin expression, early age of onset, and estrogen receptor (ER) and human epidermal growth factor receptor-2 (HER2) status were the independent factors most clearly distinguishing tumors of BRCA1 mutation carriers from other familial breast cancers. High cyclin E and low cyclin D1 expression were also independent predictors of BRCA2 mutation when compared with familial non-BRCA1/2 tumors. Most interestingly, lower frequency of high cyclin E expression independently distinguished familial non-BRCA1/2 tumors also from sporadic ones. CONCLUSIONS: Cyclin E and cyclin D1 expression distinguishes non-BRCA1/2 tumors from both sporadic and BRCA1- and BRCA2-associated tumors and may reflect different predisposition and pathogenesis in these groups.
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Biuppslag (personer, institutioner, konferenser, titlar ...)
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Blomqvist, CarlUppsala universitet,Enheten för onkologi
(författare)
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Amini, Rose-MarieUppsala universitet,Institutionen för immunologi, genetik och patologi(Swepub:uu)roseamin
(författare)
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Eerola, Hannaleena
(författare)
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Aittomäki, Kristiina
(författare)
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Heikkilä, Päivi
(författare)
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Nevanlinna, Heli
(författare)
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Uppsala universitetEnheten för onkologi
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Clinical Cancer Research14:7, s. 1976-831078-04321557-3265
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