Loss of heterozygosity in BRCA1 and BRCA2 markers and high-grade malignancy in breast cancer.
Loss of heterozygosity (LOH) in loci of the 17q21 and 13q12-13 regions can collaborate in the inactivation of BRCA1, BRCA2, and possibly other genes implicated in the pathogenesis of breast carcinomas. We investigate allelic losses in microsatellites of the BRCA1 and BRCA2 regions, and their correlations with seven pathologic parameters in 140 breast carcinomas. Those cases showing LOH in the region of the RB gene, 13q14, were excluded from the study. The LOH analysis was performed by amplifying DNA by PCR, using four markers of the 17q21 region (D17S856, D17S855, D17S1323, and D17S1327) and four markers of the 13q12-13 region (D13S290, D13S260, D13S310, and D13S267). LOH in the BRCA1 region was found in 47% of tumors, correlating significantly with estrogen receptor content (p = 0.025), progesterone receptors (p = 0.004), higher grade (p = 0.0008), peritumoral vessel invasion (p = 0.001), and lymph node metastases (p = 0.002). When we excluded the cases with LOH in the BRCA2 region and those not informative for it, the significance disappeared. In the BRCA2 region, a rate of LOH of 51% was found; it correlated significantly with estrogen receptor content (p = 0.002), progesterone receptors (p = 0.03), peritumoral vessel invasion (p = 0.005), higher grade (p = 0.002), and lymph node metastases (p = 0.001). When cases with BRCA1 losses and those not informative were excluded, again the significance disappeared. Concomitant losses in the BRCA1 and BRCA2 regions were found in 32% of cases, correlating significantly with lymph node metastases (p = 0.0002), estrogen receptor content (p = 0.003), progesterone receptors (p = 0.001), histologic grade (p = 0.01), and peritumoral vessel invasion (p = 0.0004). These results suggest that concomitant losses in both regions could have a functional effect, influencing the presence of a poor tumor pathophenotype in breast carcinomas.
Silva
J M
JM
Department of Medical Oncology, Clinica Puerta de Hierro, Madrid, Spain.
Gonzalez
R
R
Provencio
M
M
Dominguez
G
G
Garcia
J M
JM
Gallego
I
I
Palacios
J
J
España
P
P
Bonilla
F
F
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D019398:Genes, BRCA1; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity; D008207:Lymphatic Metastasis; D018895:Microsatellite Repeats; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D014157:Transcription Factors / Q000235:genetics*
D024682:BRCA2 Protein; D017931:DNA Primers; D004273:DNA, Neoplasm; D005819:Genetic Markers; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014157:Transcription Factors