Loss of heterozygosity is detected at chromosomes 1p35-36 (NB), 3p25 (VHL), 16p13 (TSC2/PKD1), and 17p13 (TP53) in microdissected apocrine carcinomasof the breast

Citation
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
Journal title
MODERN PATHOLOGY
ISSN journal
0893-3952 → ACNP
Volume
12
Issue
12
Year of publication
1999
Pages
1083 - 1089
Database
ISI
SICI code
0893-3952(199912)12:12<1083:LOHIDA>2.0.ZU;2-#
Abstract
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.