No abstract

Quantum dot bioconjugates can be used for multiplexed and quantitative detection of tumor biomarkers in cells and tissues. This new technology should have significant impact on molecular pathology if validated with traditional techniques (such as western blotting, FISH, and IHC), and with large‐scale clinical studies. In addition, it could also become the first clinical application of quantum dots.

Tuberculosis and lung cancer rarely coincide together but have been proven to have a definitive link. In this case we describe tuberculosis and adenocarcinoma diagnosed together in the same lobe of the lung. The patient was found to have an epidermal growth factor receptor exon 19 deletion, which has been shown to have an association with tuberculosis.

Oophorectomy was found to cause regression of advanced breast cancer toward the end of the 19th century. Decades later, the discovery that estrogen plays a central role in this process eventually led to two important consequences: first, different modalities were developed to suppress or antagonize estrogen; and second, the ability to detect estrogen receptor in breast cancer tissue became a predictor of response to treatment--probably the best marker for response among all solid tumors. Tamoxifen, which works by competitively antagonizing hormonal receptors in breast cancer cells, has been for the past three decades the standard of care for adjuvant therapy for any woman with hormone receptor-positive early breast cancer, regardless of nodal status or menopausal setting. But as we strive to improve the utility of antagonizing or suppressing estrogen, new modalities are being developed. In the premenopausal setting, the advent of gonadotropin hormone-releasing hormone (also known as luteinizing hormone-releasing hormone) analogues has allowed for medical and reversible suppression of ovarian function. This method has already been proven as effective as chemotherapy in preventing recurrence, and ongoing trials are aiming to better define its role in the adjuvant setting. In the postmenopausal setting, aromatase inhibitors (AIs) have revolutionized the adjuvant treatment of hormone-responsive cancers of all stages. The current standard of care has come to include AIs, as an alternative, in sequence, of after 5 years of tamoxifen. Ongoing research continues to develop agents to overcome hormonal therapy resistance.

619 Background: Conventional methods of detecting breast cancer biomarkers are hampered by a lack of adequate quantification and/or an inability to detect multiple targets on small quantities of tissue. We have previously demonstrated that estrogen receptor (ER), progesterone receptor (PR) and HER2/neu (HER2) can be detected and quantified simultaneously using antibodies (Abs) directly conjugated to nanoparticles, called quantum dots (QDs), on single breast cancer sections (ASCO 2005). We have expanded our assay to use multicolored QDs conjugated directly to Abs (QD-Abs) to detect and quantify simultaneously ER, PR, and HER2, along with 3 putative biomarkers, epidermal growth factor receptor (EGFR), mammalian target of Rapamycin (mTOR), and insulin-like growth factor receptor (IGFR), in breast cancer cell lines and human breast cancers. Methods: We used multicolored QDs directly conjugated to primary Abs to detect the 6 proteins in breast cancer cell lines (MCF-7, BT474, MDA-231) and single sections of human breast cancers. The 6 proteins were quantified using spectral separation microscopy, and compared to Western blotting. Results: We detected all 6 proteins simultaneously using QD-Abs in breast cancer cell lines and breast tumors. Using hyper-spectral imaging and wavelength-resolved spectroscopy, we separated all 6 fluorescent signals, and quantified the expression of each protein detected using QD-Abs. Quantification of the biomarkers showed good correlation with Western blotting. Conclusions: These results are proof of principle that 6 proteins can be simultaneously quantified using QD-Abs in single breast cancer sections. The use of multiplex QDs offers a novel method of determining the proteome of an individual breast cancer on single breast cancer sections. With the expanding use of targeted therapies in breast cancer, the ability to detect multiple proteins on small breast cancer specimens using QD-Abs, could allow not only the accurate selection of therapy, but a unique method of determining the activity of specific targeted agents. No significant financial relationships to disclose.