Ca Breast Cancer

Only available on StudyMode
  • Download(s) : 32
  • Published : April 9, 2013
Open Document
Text Preview
Modern Pathology (2011), 1–10
& 2011 USCAP, Inc. All rights reserved 0893-3952/11 $32.00

MYC gene amplification is often acquired
in lethal distant breast cancer metastases
of unamplified primary tumors
Aatur D Singhi1, Ashley Cimino-Mathews1, Robert B Jenkins2, Fusheng Lan2, Stephanie R Fink2, Hind Nassar1, Russell Vang1, John H Fetting3, Jessica Hicks1, Saraswati Sukumar3, Angelo M De Marzo1,3 and Pedram Argani1,3 1

Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA; 2Department of Laboratory Medicine and Pathology and Laboratory Genetics, Mayo Clinic, Rochester, MN, USA and 3
Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

In breast cancer, amplification of MYC is consistently observed in aggressive forms of disease and correlates with poor prognosis and distant metastases. However, to date, a systematic analysis of MYC amplification in metastatic breast cancers has not been reported. Specifically, whether the MYC amplification status may change in metastases in comparison to the corresponding primary breast tumor, and potential variability among different metastases within the same patient have also not been assessed. We generated single patient tissue microarrays consisting of both primary breast carcinomas and multiple matched systemic metastases from 15 patients through our previously described rapid autopsy program. In total, the 15 tissue microarrays contained 145 primary tumor spots and 778 spots derived from 180 different metastases. In addition, two separate tissue microarrays were constructed composed of 10 matched primary breast cancers and corresponding solitary metastases sampled not at autopsy but rather in routine surgical resections. These two tissue microarrays totaled 50 primary tumor spots and 86 metastatic tumor spots. For each case, hormone receptor status, HER2/neu, EGFR and CK5/6 expression were assessed, and the cases were characterized as luminal, basal-like or HER2 based on published criteria. Both fluorescence in situ hybridization and immunohistochemistry for MYC was performed on all cases. Of the 25 cases, 24 were evaluable. While 4 of 24 primary tumors (16%) demonstrated MYC amplification, an additional 6 (25% of total evaluable cases) acquired MYC amplification in their systemic metastases. Of note, there was remarkably little heterogeneity in MYC copy number among different metastases from the same patient. MYC immunoreactivity was increased in metastases relative to matched primaries in the surgical cohort, although there was no perfect correlation with MYC amplification. In conclusion, amplification of MYC is a frequent event in breast cancer, but occurs more frequently as a diffuse, acquired event in metastatic disease than in the corresponding primary. These observations underscore the importance of MYC in breast cancer progression/metastasis, as well as its relevance as a potential therapeutic target in otherwise incurable metastatic disease. Modern Pathology advance online publication, 4 November 2011; doi:10.1038/modpathol.2011.171 Keywords: breast cancer; fluorescent in situ hybridization; MYC

Breast cancer is well known to be highly variable at
both the clinical and genetic levels. Many cases
progress rapidly with short survival, whereas others
grow indolently with relatively good outcome after
Correspondence: Dr P Argani, MD, The Johns Hopkins Hospital, 401 N. Broadway, Weinberg 2242, Baltimore, MD 21231-2410,
USA.
E-mail: pargani@jhmi.edu
Received 22 July 2011; revised 31 August 2011; accepted 31
August 2011; published online 4 November 2011
www.modernpathology.org

treatment. Not surprisingly, at the molecular level,
breast cancer is also characterized by a diverse
number of genetic abnormalities including unbalanced chromosomal rearrangements, gene amplifications and deletions. Some of these genetic alterations have been shown to be associated with
tumors of distinct histological types...
tracking img