Correlation between BRCA1 expression and clinicopathological factors including brain metastases in patients with non-small-cell lung cancer

被引:4
|
作者
Gachechiladze, Mariam [1 ]
Uberall, Ivo [1 ,2 ]
Kolek, Vitezslav [3 ,4 ]
Klein, Jiri [4 ,5 ]
Krejci, Veronika [1 ,2 ]
Stastna, Jitka [1 ]
Radova, Lenka [4 ,6 ,7 ]
Fridman, Eddie [8 ]
Skarda, Josef [1 ,2 ]
机构
[1] Palacky Univ Olomouc, Fac Med & Dent, Dept Pathol, Lab Mol Pathol, Olomouc, Czech Republic
[2] Palacky Univ Olomouc, Fac Med & Dent, IMTM, Olomouc, Czech Republic
[3] Palacky Univ Olomouc, Fac Med & Dent, Dept TB & Resp Dis, Olomouc, Czech Republic
[4] Univ Hosp Olomouc, Olomouc, Czech Republic
[5] Palacky Univ Olomouc, Fac Med & Dent, Dept Surg 1, Olomouc, Czech Republic
[6] Palacky Univ Olomouc, Fac Med & Dent, Dept Pediat, Expt Med Lab, Olomouc, Czech Republic
[7] Palacky Univ Olomouc, Fac Med & Dent, Dept Oncol, Expt Med Lab, Olomouc, Czech Republic
[8] Sheba Hlth Med Ctr, Dept Pathol, Tel Hashomer, Israel
来源
BIOMEDICAL PAPERS-OLOMOUC | 2013年 / 157卷 / 03期
关键词
BRCA1; brain metastases; non-small-cell lung cancer; RESISTANCE; REPAIR; CHEMORESISTANCE; CISPLATIN; SURVIVAL; ERCC1;
D O I
10.5507/bp.2012.099
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Background. Previously identified as a breast and ovarian cancer susceptibility gene, BRCA1 has gained major scientific interest as a potential prognostic and/or predictive marker for various tumors, including non-small-cell lung cancer (NSCLC), the leading cause of cancer related mortality worldwide. BRCA1 plays a central role in DNA damage response (DDR. It undergoes phosphorylation by various DDR kinases at different serine residues, of which ser1524 is known to be specifically phosphorylated by ATM in response to genotoxic stress. Methods. We performed BRCA1 immunohistochemistry on several tissue microarrays (TMAs) of 113 early (I, II stage) and advanced (III, IV stage) NSCLCs, using MS110 antibody against the BRCA1 N-terminal and S1524 antibody against the phosphorylated form of BRCA1 protein at ser1524 (Abcam). Patients with III and IV stage disease were treated by adjuvant cisplatin-based chemotherapy. Staining results were correlated with overall survival (OS), disease free survival (DFS) and with the occurrence of brain metastases. Results. BRCA1 S1524 nuclear positivity was significantly correlated with longer OS and DFS in stage I and II patients (P<0.05), while OS and DFS were shorter in S1524 positive stage III and IV patients (P<0.05). No significant correlation was found with brain metastases. Conclusion. The results show that BRCA1 phosphorylaton, at least in ser1524, differentiates the fate of early and advanced NSCLC as well as response to chemotherapy, but the underlying mechanisms are not completely understood. Detection of phosphorylated forms of BRCA1 might serve as a useful prognostic and predictive marker for patients with NSCLC.
引用
收藏
页码:227 / 232
页数:6
相关论文
共 50 条
  • [31] FACTORS PREDICTING BRAIN METASTASES IN PATIENTS WITH NON-SMALL CELL LUNG CANCER
    Hsiao, S.
    Chung, C.
    Liu, H. E.
    ANNALS OF ONCOLOGY, 2012, 23 : 428 - 429
  • [32] The risk factors for brain metastases in patients with non-small cell lung cancer
    Lim, Jun Hyeok
    Um, Sang-Won
    ANNALS OF TRANSLATIONAL MEDICINE, 2018, 6
  • [33] Effect of BRCA1 Haplotype on Survival of Non-Small-Cell Lung Cancer Patients Treated With Platinum-Based Chemotherapy
    Kim, Hong-Tae
    Lee, Jong-Eun
    Shin, Eun-Soon
    Yoo, Yeon-Kyeong
    Cho, Jae-Hwa
    Yun, Min-Hye
    Kim, Yeul-Hong
    Kim, Se-Kyu
    Kim, Hyun-Jung
    Jang, Tae-Won
    Kwak, Seung-Min
    Kim, Chul-Soo
    Ryu, Jeong-Seon
    JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (36) : 5972 - 5979
  • [34] BRCA1, LMO4, and CtIP mRNA Expression in Erlotinib-Treated Non-Small-Cell Lung Cancer Patients with EGFR Mutations
    Karachaliou, Niki
    Costa, Carlota
    Gimenez-Capitan, Ana
    Angel Molina-Vila, Miguel
    Bertran-Alamillo, Jordi
    Mayo, Clara
    Massuti, Bartomeu
    Majem, Margarita
    Carcereny, Enric
    Moran, Teresa
    Javier Sanchez, Jose
    Viteri, Santiago
    Gasco, Amaya
    Wannesson, Luciano
    Souglakos, John
    Jimeno, Jose
    Rosell, Rafael
    JOURNAL OF THORACIC ONCOLOGY, 2013, 8 (03) : 295 - 300
  • [35] Erlotinib therapy in a patient with non-small-cell lung cancer and brain metastases
    Giuseppe Altavilla
    Carmela Arrigo
    Maria Carmela Santarpia
    Giuseppe Galletti
    Giovanni Picone
    Grazia Marabello
    Chiara Tomasello
    Vincenzo V. Pitini
    Journal of Neuro-Oncology, 2008, 90 : 31 - 33
  • [36] A case report of a non-small-cell lung cancer patient with brain metastases
    Kowalski, DM
    Zajda, K
    Krzakowski, M
    BRITISH JOURNAL OF CANCER, 2003, 89 : S30 - S30
  • [37] Immune Checkpoint Inhibitors for Brain Metastases of Non-Small-Cell Lung Cancer
    Ashinuma, H.
    Shingyoji, M.
    Iuchi, T.
    Yoshida, Y.
    Setoguchi, T.
    Hasegawa, Y.
    Sakaida, T.
    JOURNAL OF THORACIC ONCOLOGY, 2017, 12 (11) : S2420 - S2420
  • [38] Brain metastases from non-small-cell lung cancer: is there room for improvement?
    Franceschi, Enrico
    Brandes, Alba A.
    EXPERT REVIEW OF ANTICANCER THERAPY, 2012, 12 (04) : 421 - 423
  • [39] BEVACIZUMAB FOR ACTIVE BRAIN METASTASES FROM NON-SMALL-CELL LUNG CANCER
    DeBraganca, Kevin C.
    Ney, Douglas E.
    Kris, Mark G.
    Nolan, Craig P.
    Lassman, Andrew B.
    NEURO-ONCOLOGY, 2009, 11 (05) : 626 - 627
  • [40] Erlotinib therapy in a patient with non-small-cell lung cancer and brain metastases
    Altavilla, Giuseppe
    Arrigo, Carmela
    Santarpia, Maria Carmela
    Galletti, Giuseppe
    Picone, Giovanni
    Marabello, Grazia
    Tomasello, Chiara
    Pitini, Vincenzo V.
    JOURNAL OF NEURO-ONCOLOGY, 2008, 90 (01) : 31 - 33