PET of HER2-Positive Pulmonary Metastases with 18F-ZHER2:342 Affibody in a Murine Model of Breast Cancer: Comparison with 18F-FDG.

PET of HER2-Positive Pulmonary Metastases with 18F-ZHER2:342 Affibody in a Murine Model of Breast Cancer: Comparison with 18F-FDG.

J Nucl Med. 2012 May 11;

Authors: Kramer-Marek G, Bernardo M, Kiesewetter DO, Bagci U, Kuban M, Omer A, Zielinski R, Seidel J, Choyke P, Capala J

Abstract
Targeted therapies often depend on the expression of the target present in the tumor. This expression can be difficult to ascertain in widespread metastases. (18)F-FDG PET/CT, although sensitive, is nonspecific for particular tumor markers. Here, we compare the use of a human epidermal growth factor receptor 2 (HER2)-specific (18)F-Z(HER2)(:342)-Affibody and (18)F-FDG in HER2-expressing pulmonary metastases in a murine model of breast cancer. METHODS: The lung metastasis model was established by intravenous injection of MDA-MB-231(HER2)-Luc human breast cancer cells into the tail vein. Bioluminescence imaging was used to evaluate metastasis progression. Uptake of (18)F-Z(HER2)(:342)-Affibody and (18)F-FDG was confirmed by coregistration of the PET images with MR and CT images. At the end of the study, the presence of neoplastic cells and HER2 expression in lung tissues, and distribution of the tracer, were assessed ex vivo by immunohistochemistry and autoradiography. RESULTS: (18)F-Z(HER2)(:342)-Affibody successfully targeted HER2-positive lesions in the lung and allowed detection of metastases as early as 9 wk after injection of cells. In contrast, (18)F-FDG uptake was often masked by surrounding inflammatory changes and was nonspecific for HER2 expression. HER2 expression at a cellular level correlated well with tracer uptake on autoradiography. CONCLUSION: (18)F-Z(HER2)(:342)-Affibody is a promising tracer for evaluation of HER2 status of breast cancer metastases and is more specific for detecting HER2-positive lesions than (18)F-FDG.

PMID: 22582046 [PubMed - as supplied by publisher]

Tags: chip, custom antibodies, elisa, immunoprecipitation, western blots

HER2-Positive Male Breast Cancer with Thyroid Cancer: an Institutional Report and Review of Literature.

Ann Clin Lab Sci. 2012;42(2):135-9

Authors: Bardhan P, Bui MM, Minton S, Loftus L, Carter WB, Laronga C, Ismail-Khan R

Abstract
We report a rare finding of two male breast cancer patients with HER2-positive breast cancer who also developed thyroid cancer. We reviewed 45 male breast cancer patients treated in our institution from 2003 to 2008. Only five male breast cancer patients were HER2-positive. In reviewing the published data, we found no cases of thyroid cancer and concurrent breast cancer in men. However, breast cancer and thyroid cancer have shown close association in women. This finding therefore provokes speculation as to whether we should investigate whether women with HER2-positive breast cancer are at a higher risk for thyroid cancer. Although this observation seems to be clinically prevalent, publications are sparse in clinical research areas linking thyroid cancer to breast cancer.

PMID: 22585608 [PubMed - in process]

Tags: chip, custom antibodies, elisa, immunoprecipitation, western blots

Polymorphism rs4919510:C>G in Mature Sequence of Human MicroRNA-608 Contributes to the Risk of HER2-Positive Breast Cancer but Not Other Subtypes.

PLoS One. 2012;7(5):e35252

Authors: Huang AJ, Yu KD, Li J, Fan L, Shao ZM

Abstract
BACKGROUND: A few polymorphisms are located in the mature microRNA sequences. Such polymorphisms could directly affect the binding of microRNA to hundreds of target mRNAs. It remains unknown whether rs4919510:C>G located in the mature miR-608 alters breast cancer susceptibility.
METHODS: The association of rs4919510:C>G with risk and pathologic features of breast cancer were investigated in two independent case-control studies, the first set including 1,138 sporadic breast cancer patients (including 927 invasive ductal carcinoma patients, 777 of them with known subtypes: 496 luminal-like, 133 HER2-positive, and 148 triple-negative) and 1,434 community-based controls, and the second set including 294 familial/early-onset breast cancer patients and 500 hospital-based cancer-free controls. Odds ratios (ORs) were estimated by logistic regression. Predicted targets of miR-608 and complementary sequences containing rs4919510:C>G were surveyed to reveal potential pathological mechanism.
RESULTS: In the first set, although rs4919510:C>G was unrelated to breast cancer in general patients, variant genotypes (CG/GG) were specifically associated with increased risk of HER2-positive subtype (Adjusted OR = 1.97, 95% CI, 1.34-2.90 in the recessive model). Variant G-allele was the risk allele with OR of 1.62 (95% CI, 1.23-2.15). Patients carrying GG-genotype also had larger HER2-positive tumors (P for Kruskal-Wallis test = 0.006). The relationship between rs4919510:C>G and risk of HER2-positive subgroup was validated in the second set (Bonferroni corrected P = 0.06). The adjusted combined OR (total 164 HER2-positive cases) in the recessive model was 1.97 (95% CI, 1.43-2.72) for GG genotype (corrected P = 1.1×10(-4)). Bioinformatic analysis indicated that, HSF1, which is required for HER2-induced tumorigenesis, might be a target of miR-608. The minimum free-energy of ancestral-miR-608 (C-allele) binding to HSF1 is -35.9 kcal/mol, while that of variant-form (G-allele) is -31.5 kcal/mol, indicating a lower affinity of variant-miR-608 to HSF1 mRNA.
CONCLUSION: rs4919510:C>G in mature miR-608 may influence HER2-positive breast cancer risk and tumor proliferation.

PMID: 22586447 [PubMed - in process]

Tags: chip, custom antibodies, elisa, immunoprecipitation, western blots