Loss of heterozygosity is detected at chromosomes 1p35-36 (NB), 3p25 (VHL), 16p13 (TSC2/PKD1), and 17p13 (TP53) in microdissected apocrine carcinomasof the breast
Ra. Lininger et al., Loss of heterozygosity is detected at chromosomes 1p35-36 (NB), 3p25 (VHL), 16p13 (TSC2/PKD1), and 17p13 (TP53) in microdissected apocrine carcinomasof the breast, MOD PATHOL, 12(12), 1999, pp. 1083-1089
Citations number
40
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Introduction: Apocrine carcinomas of the breast are an unusual special cate
gory of predominantly AR+, ER-, and PR- breast cancer, characterized by cel
ls with abundant, eosinophilic cytoplasm and nuclei with often prominent nu
cleoli. To further investigate these lesions, loss of heterozygosity (LOH)
was evaluated at multiple chromosomal loci, including loci frequently mutat
ed in breast cancer. Materials and Methods: Twenty-five intraductal apocrin
e carcinomas, 11 invasive apocrine carcinomas, and six apocrine hyperplasia
s were retrieved from the files of the Armed Forces Institute of Pathology
(Washington, DC) and Fairfax Hospital (Fairfax, VA). Cells from lesional as
well as normal tissues were microdissected. LOH was performed at a number
of chromosomal loci, including loci commonly altered in breast cancer: 1p35
-36 (NB), 3p25.5 (VHL), 8p12 (D8S136), 9p21 (p16), 11p13 (D11S904), 11q13 (
INT-2 and PYGM), 16p13.3 (TSC1/PKD1 gene region), 17p13 (TP53), 17q13 (NM23
), and 22q12 (D22S683). Results: Among informative in situ and invasive apo
crine carcinomas, LOH was present in 33% of 15 cases for 17p13 (TP53), as w
ell as 36% of 14 cases for 3p25 (VHL), 30% of 10 cases for 1p35-36 (NB), an
d 27% of 11 cases for 16p13.3 (TSC2/PKD1). A higher frequency of LOH was no
ted among invasive apocrine carcinomas (30 to 50%) compared with in situ ap
ocrine carcinomas (23 to 33%) at these loci. LOH was present simultaneously
for TP53 and either VHL or NE in five cases. Infrequent (less than or equa
l to 12%) or absent LOH was detected at the remaining loci, including sever
al loci commonly mutated in breast cancer (i.e., INT2, PYGM, and NM23). LOH
was not detected in any of the six apocrine hyperplasias. Conclusion: Am i
ntermediate frequency of allelic loss was detected at multiple tumor suppre
ssor gene loci, including 17p13 (TP53), as well as 1p35-336 (NB), 3p25 (VHL
), and 16p13 (PKD1/TSC2), in apocrine carcinomas of the breast, with a high
er overall frequency of LOH noted among invasive tumors compared with in si
tu tumors. Aside from LOH at p53, LOH was infrequent or absent at several o
ther loci commonly mutated in breast cancer. This preliminary molecular evi
dence supports immunohistochemical data that apocrine carcinomas of the bre
ast may possess unique mechanisms of carcinogenesis, compared with ordinary
ductal carcinomas. However, further study is needed to support this assert
ion and to determine if the LOH detected is truly etiologic or if it is the
result of genetic progression.