Different expression of P14ARF defines two groups of breast carcinomas in terms of TP73 expression and TP53 mutational status.
In 95 breast carcinomas, we investigated P14ARF and TP73 mRNA expression and their relationship to TP53 mutations, determined by an immunohistochemical method, studying several clinicopathologic features of the tumors. P14ARF and TP73 mRNA levels were determined by semiquantitative reverse transcription polymerase chain reaction (RT-PCR), using beta-actin as a control. P14ARF was overexpressed in 19% of the cases and underexpressed in 24%. TP73 was overexpressed in 22% of the tumors, and normal levels were found in the remaining 78%. The analysis of TP53 showed positive immunostaining in 38% of cases. The association of P14ARF and TP73 overexpression was statistically significant, as was the association between positive TP53 staining and TP73 overexpression. P14ARF was related to TP53 only in those cases in which there was low expression of P14ARF. Concomitant overexpression of P14ARF and TP73 was statistically related to positive TP53 immunostaining. The analysis of concomitant P14ARF and TP73 overexpression and clinicopathologic parameters of the tumors showed a statistically significant difference with respect to peritumoral vessel invasion (P = 0.01), lymph node metastasis (P = 0.03), negative ERBB2 expression (P = 0.005), and more advanced pathologic stages (P = 0.03). These results suggest that overexpression of P14ARF and TP73 could be implicated in breast carcinoma tumorigenesis and, ultimately, in the phenotypic features of these lesions.
Domínguez
G
G
Department of Medical Oncology, Clínica Puerta de Hierro, Madrid, Spain.
Silva
J
J
Silva
J M
JM
García
J M
JM
Larrondo
F J
FJ
Vargas
J
J
Sanfrutos
L
L
Provencio
M
M
España
P
P
Bonilla
F
F
D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D012689:Sequence Homology, Nucleic Acid; D000072160:Tumor Protein p73; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins