TP53 mutation analyses on breast carcinomas: a study of paraffin-embedded archival material.
The aim of this investigation was to examine the possibility of analysing TP53 mutations in archival paraffin-embedded material with the constant denaturant gel electrophoresis (CDGE) method. We extracted DNA from 193 archival primary breast carcinoma samples, diagnosed in 1981-83; further analysis was possible for 186 of these. TP53 mutations in exons 5-8 were detected with CDGE in 30 samples (16.1%) and 17 of these mutations were confirmed by sequencing. Immunohistochemistry demonstrated TP53 nuclear accumulation in 58 tumours (31%). A strong association between the presence of TP53 mutations and TP53 immunostaining was observed (P < 0.001). Our mutation and immunohistochemistry results are in agreement with other findings based on fresh tumour tissue. TP53 abnormalities were significantly related to high S-phase fraction, low oestrogen receptor (ER) content and high tumour grade. Survival of patients with TP53 abnormalities, in the group as a whole, did not differ from patients with normal TP53. Our study did, however, show that patients with abnormal TP53 had a significantly shorter post-recurrence survival (P = 0.005) than patients with normal TP53.
Gretarsdottir
S
S
Molecular and Cell Biology Research Laboratory, Icelandic Cancer Society, Reykjavik, Iceland.
Tryggvadottir
L
L
Jonasson
J G
JG
Sigurdsson
H
H
Olafsdottir
K
K
Agnarsson
B A
BA
Ogmundsdottir
H
H
Eyfjörd
J E
JE
D000595:Amino Acid Sequence; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000401:mortality / Q000473:pathology; D018275:Carcinoma, Lobular / Q000235:genetics / Q000401:mortality / Q000473:pathology; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification*; D018572:Disease-Free Survival; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D016158:Genes, p53; D006652:Histological Techniques; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness; D010232:Paraffin; D011003:Ploidies; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012008:Recurrence; D016196:S Phase; D017384:Sequence Deletion; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D004273:DNA, Neoplasm; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; D010232:Paraffin