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).
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.
Available from: Saeed Reza Ghaffari
- "This finding undoubtedly confirms the fact that the average number of chromosomal abrasions increases with invasion and metastasis to lymph nodes (Albertson et al., 2003; Aubele et al., 2000; Buerger et al., 2000). The pattern of aberrations at some chromosomal loci in unspecific breast cancer (+1q, +8q, +16q, +17q, +20q) differs significantly from carcinomas stratified by grade (Damiai et al., 1999; Selim AG et al., 2001); grade 1 (well differentiated) carcinomas frequently demonstrate gain of +1q and loss of -16q as well as an overall low incidence of alteration and amplification while higher grade (grade2, 3), intermediate, and poorly differentiated carcinomas exhibit more genetic alterations, and more amplifications (+8q, +17q, +20q), and the frequency of -16q loss as compared to grade 1 carcinomas is significantly reduced (Damiani et al., 1999; Selim et al., 2001). Due to the small sample size, we were not able to find any correlation between any specific chromosomal abrasion and tumor grading. "
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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
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ABSTRACT: This issue of The Breast includes an elegant study by Selim et al. on c-myc gene amplification and protein overexpression in apocrine metaplasia (APM) and apocrine adenosis (AA) of the breast using paraffin-embedded tissue. In their report, the authors observe that all cases of APM and AA harbored c-myc protein overexpression, but no definitive gene amplification was found. Most importantly, they observed that the percentage of cells expressing c-myc in APM and AA was significantly correlated with cell proliferation, as assessed by Ki-67 immunolabeling index. On the basis of their findings and of previously reported studies, the authors suggest that c-myc overexpression occurs in early stages of breast carcinogenesis, that c-myc gene amplification may be a late event, and that in APM and AA c-myc overexpression is related to cell proliferation. Selim et al. findings have brought to our attention two thorny but rather important issues regarding current concepts of apocrine changes and their association with breast carcinomas, and also the role of c-myc in breast carcinogenesis.
The Breast 01/2003; 11(6):463-5. DOI:10.1054/brst.2002.0480 · 2.38 Impact Factor
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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 · 9.39 Impact Factor
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