Details

Autor(en) / Beteiligte

• HONRADO, Emiliano
• OSORIO, Ana
• LERMA, Enrique
• KALLIONIEMI, Anne
• RIVAS, Carmen
• FOULKES, William D
• NEVANHNNA, Heli
• BENITEZ, Javier
• PALACIOS, José
• MILNE, Roger L
• SANCHEZ, Lydia
• DIEZ, Orland
• CAZORLA, Alicia
• SYRJAKOSKI, Kirsi
• HUNTSMAN, David
• HEIKKILA, Paivi

Titel

Immunohistochemical Expression of DNA Repair Proteins in Familial Breast Cancer Differentiate BRCA2-Associated Tumors

Ist Teil von

• Journal of clinical oncology, 2005-10, Vol.23 (30), p.7503-7511

Ort / Verlag

Baltimore, MD: American Society of Clinical Oncology

Erscheinungsjahr

2005

Quelle

MEDLINE

Beschreibungen/Notizen

• Morphologic and immunohistochemical studies of familial breast cancers have identified specific characteristics associated with BRCA1 mutation-associated tumors when compared with BRCA2 and non-BRCA1/2 tumors, but have not identified differences between BRCA2 and non-BRCA1/2 tumors. Because BRCA1 and BRCA2 genes participate in the DNA repair pathway, we have performed an immunohistochemical study with markers related to this pathway to establish the profile of the three groups. We have studied two tissue microarrays that include 103 familial and 104 sporadic breast tumors, with a panel of DNA repair markers including ATM, CHEK2, RAD51, RAD50, XRCC3, and proliferating cell nuclear antigen. We found more frequent expression of CHEK2 in BRCA1 and BRCA2 tumors than in non-BRCA1/2 and sporadic tumors. We found absence of nuclear expression and presence of cytoplasmic expression of RAD51 in BRCA2 tumors that differentiate them from other familial tumors. We validated these results with a new series of patient cases. The final study with 253 familial patient cases (74 BRCA1, 71 BRCA2, 108 non-BRCA1/2), and 288 sporadic patient cases, has allowed us to confirm our preliminary results. Because BRCA2 tumors present a specific immunohistochemical profile for RAD51 and CHEK2 markers that is different from non-BRCA1/2 tumors, we have built a multivariate model with these markers that distinguish both tumors with an estimated probability of at least 76%. Our results suggest that BRCA2 tumors demonstrate more cytoplasmic and less nuclear RAD51 staining, and increased CHEK2 staining. This pattern may distinguish BRCA2 from familial non-BRCA1/2 tumors.