High RAD51 mRNA expression characterize estrogen receptor-positive/progesteron receptor-negative breast cancer and is associated with patient's outcome.
Mutations in DNA double-strand breaks (DSB) repair genes are involved in the pathogenesis of hereditary mammary tumors, it is, however, still unclear whether defects in this pathway may play a role in sporadic breast cancer. In this study, we initially determined mRNA expression of 15 DSB related genes by reverse transcription quantitative polymerase chain reaction in paired normal tissue and cancer specimen from 20 breast cancer cases to classify them into homogeneous clusters. G22P1/ku70, ATR and RAD51 genes were differentially expressed in the three branches recognized by clustering analysis. In particular, a breast cancer subgroup characterized by high RAD51 mRNA levels and estrogen receptor (ER)-positive/progesteron receptor (PR)-negative phenotype was identified. This result was confirmed by the analysis of G22P1/ku70, ATR and RAD51 mRNA levels on paired normal and tumor specimens from an extended breast cancer cohort (n = 75). RAD51 mRNA levels were inversely associated with PR status (p = 0.02) and the highest levels were, indeed, detected in ER-positive/PR-negative tumors (p = 0.03). RAD51 immunostaining of a tissue microarray confirmed the inverse relationship between high RAD51 expression and negative PR status (p = 0.002), as well as, the association with ER-positive/PR-negative phenotype (p = 0.003). Interestingly, the analysis of microarray expression data from 295 breast cancers indicate that RAD51 increased mRNA expression is associated with higher risk of tumor relapse, distant metastases and worst overall survival (p = 0.015, p = 0.009 and p = 0.013 respectively). Our results suggest that RAD51 expression determination could contribute to a better molecular classification of mammary tumors and may represent a novel tool for evaluating postoperative adjuvant therapy for breast cancer patients.
Laboratory of Oncology, Research Department, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy.
Raffaela
R
Barbano
Massimiliano
M
Copetti
Giuseppe
G
Perrone
Valerio
V
Pazienza
Lucia Anna
LA
Muscarella
Teresa
T
Balsamo
Clelia Tiziana
CT
Storlazzi
Maria
M
Ripoli
Monica
M
Rinaldi
Vanna Maria
VM
Valori
Tiziana Pia
TP
Latiano
Evaristo
E
Maiello
Pietro
P
Stanziale
Massimo
M
Carella
Alessandra
A
Mangia
Fabio
F
Pellegrini
Michele
M
Bisceglia
Andrea Onetti
AO
Muda
Vittorio
V
Altomare
Roberto
R
Murgo
Vito Michele
VM
Fazio
Paola
P
Parrella
D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D018450:Disease Progression; D047628:Estrogen Receptor alpha; D005260:Female; D006801:Humans; D009376:Neoplasms, Hormone-Dependent; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D051135:Rad51 Recombinase / Q000235:genetics*; D011980:Receptors, Progesterone / Q000378:metabolism; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D011980:Receptors, Progesterone; C495153:RAD51 protein, human; D051135:Rad51 Recombinase