Loss of heterozygosity and allelic imbalance in apocrine adenosis of the breast.

Department of Histopathology, St Bartholomew's and the Royal London School of Medicine and Dentistry, St Bartholomew's Hospital, London, United Kingdom.
Cancer Detection and Prevention (Impact Factor: 2.52). 02/2001; 25(3):262-7.
Source: PubMed

ABSTRACT Recently, there have been studies suggesting that apocrine adenosis of the breast is a putative precancerous lesion, despite the generally held view that apocrine adenosis is benign. Because apocrine adenosis is almost always present as a small area or areas, it cannot be easily studied by conventional methods. In this study, areas of apocrine adenosis were microdissected from archival paraffin-embedded tissue to examine loss of heterozygosity and allelic imbalance compared with normal breast tissue epithelium from the same patients. Seventeen cases of apocrine adenosis, four associated with carcinoma, were analyzed using polymorphic microsatellite markers and polymerase chain reaction for loss of heterozygosity/allelic imbalance at eight loci that were reported to show allele loss or imbalance in invasive and in situ breast cancer. Loss of heterozygosity/allelic imbalance was detected in six of 17 cases of apocrine adenosis; three of 12 (25%) informative cases at 1p (MYCL1), two of seven (28.6%) at 11q (INT2), one of three (33.3%) at 13q (D13S267), two of 12 (16.7%) at 16q (D16S539), and two of 10 (20%) at 17q (D17S250). Neither loss of heterozygosity nor allelic imbalance has been identified at 1p (D1S252), 17p (TP53), or 17p (D17S513). In two of the four cases associated with carcinoma, loss of heterozygosity/allelic imbalance was seen in the same allele as in the synchronous carcinoma. These results suggest that molecular alterations, such as loss of heterozygosity and allelic imbalance, identified in apocrine adenosis may constitute an early event in the pathogenesis of breast cancer; reinforcing the possibility of apocrine adenosis being a putative precancerous lesion.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Breast cancer is one of the most common cancers in women; however, due to the complexity of chromosomal changes, limited data are available regarding chromosomal constitution. In this study, Comparative Genomic Hybridization (CGH) was used on 16 Iranian patients diagnosed with invasive ductal breast carcinomas. 12 samples had abnormal CGH results (75%), including 21 types of chromosomal imbalance. The most prevalent were chromosomal gain of +1q, +17q, +8q and chromosomal loss of -13q. All three cases with DNA loss at chromosome 13q (-13q) had lymph node metastasis. CGH is able to detect chromosomal abnormalities which are difficult to identify by conventional cytogenetic techniques. More studies on a larger sample size may help to confirm or rule out any possible correlation between 13q monosomy and lymph node metastasis, which could result in establishing new strategies for prevention and early detection of invasive breast tumors.
    Asian Pacific journal of cancer prevention: APJCP 01/2007; 9(1):66-70. · 2.51 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The molecular mechanisms underlying the development of breast cancer in general, and estrogen-associated breast carcinogenesis in particular, are not completely understood. There are three mechanisms considered responsible for the carcinogenicity of estrogens in the human breast: (i) receptor-mediated hormonal activity, which stimulates cellular proliferation, resulting in more opportunities for accumulation of the genetic damage that leads to carcinogenesis; (ii) a cytochrome P450-mediated metabolic activation, which elicits direct genotoxic effects by increasing mutation rates; and (iii) the induction of aneuploidy by estrogen. In this article, we concentrate on discussing the role of estrogen receptors and the metabolic activation of 17beta-estradiol (E(2)) as mechanisms of breast cancer initiation.
    Trends in Endocrinology and Metabolism 08/2004; 15(5):211-4. DOI:10.1016/j.tem.2004.05.007 · 8.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Molecular analysis of invasive breast cancer and its precursors has furthered our understanding of breast cancer progression. In the past few years, new multi-step pathways of breast cancer progression have been delineated through genotypic-phenotypic correlations. Nuclear grade, more than any other pathological feature, is strongly associated with the number and pattern of molecular genetic abnormalities in breast cancer cells. Thus, there are two distinct major pathways to the evolution of low- and high-grade invasive carcinomas: whilst the former consistently show oestrogen receptor (ER) and progesterone receptor (PgR) positivity and 16q loss, the latter are usually ER/PgR-negative and show Her-2 overexpression/amplification and complex karyotypes. The boundaries between the evolutionary pathways of well-differentiated/low-grade ductal and lobular carcinomas have been blurred, with changes in E-cadherin expression being one of the few distinguishing features between the two. In addition, lesions long thought to be precursors of breast carcinomas, such as hyperplasia of usual type, are currently considered mere risk indicators, whilst columnar cell lesions are now implicated as non-obligate precursors of atypical ductal hyperplasia (ADH) and well-differentiated ductal carcinoma in situ (DCIS). However, only through the combination of comprehensive morphological analysis and cutting-edge molecular tools can this knowledge be translated into clinical practice and patient management.
    The Journal of Pathology 01/2005; 205(2):248-54. DOI:10.1002/path.1691 · 7.33 Impact Factor