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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

Aaltonen, Kirsimari (författare)
Blomqvist, Carl, (författare)
Uppsala universitet, Enheten för onkologi
Amini, Rose-Marie, (författare)
Uppsala universitet, Institutionen för immunologi, genetik och patologi
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Eerola, Hannaleena (författare)
Aittomäki, Kristiina (författare)
Heikkilä, Päivi (författare)
Nevanlinna, Heli (författare)
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Uppsala universitet Medicinska och farmaceutiska vetenskapsområdet. Medicinska fakulteten. Institutionen för onkologi, radiologi och klinisk immunologi. Enheten för onkologi. (creator_code:org_t)
Uppsala universitet Medicinska och farmaceutiska vetenskapsområdet. Medicinska fakulteten. Institutionen för immunologi, genetik och patologi. (creator_code:org_t)
2008
Engelska.
Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 14:7, s. 1976-83
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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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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MEDICIN OCH HÄLSOVETENSKAP  (hsv//swe)
MEDICAL AND HEALTH SCIENCES  (hsv//eng)

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MEDICINE
MEDICIN

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