Necrotizing meningoencephalitis (NME) is a disorder of Pug Dogs that appears to have an immune etiology and high heritability based on population studies. The present study was undertaken to identify a genetic basis for the disease. A genome-wide association scan with single tandem repeat (STR) markers showed a single strong association near the dog leukocyte antigen (DLA) complex on CFA12. Fine resolution mapping with 27 STR markers on CFA12 further narrowed association to the region containing DLA-DRB1, -DQA1 and, -DQB1 genes. Sequencing confirmed that affected dogs were more likely to be homozygous for specific alleles at each locus and that these alleles were linked, forming a single high risk haplotype. The strong DLA class II association of NME in Pug Dogs resembles that of human multiple sclerosis (MS). Like MS, NME appears to have an autoimmune basis, involves genetic and nongenetic factors, has a relatively low incidence, is more frequent in females than males, and is associated with a vascularly orientated nonsuppurative inflammation. However, NME of Pug Dogs is more aggressive in disease course than classical human MS, appears to be relatively earlier in onset, and involves necrosis rather than demyelination as the central pathobiologic feature. Thus, Pug Dog encephalitis (PDE) shares clinical features with the less common acute variant forms of MS. Accordingly, NME of Pug Dogs may represent a naturally occurring canine model of certain idiopathic inflammatory disorders of the human central nervous system.

We recently reported the use of matrix-assisted laser desorption ionization (MALDI) Fourier transformation mass spectrometry (FTMS) techniques to identify unique glycan markers in ovarian cancer cell lines which may be biomarkers for diagnosis of ovarian cancer. Glycan markers and CA125 levels are compared in a series of ovarian cancer patients and normal control subjects. Oligosaccharides (OS) were cleaved from the serum glycoproteins and isolated using solid phase extraction. MALDI-FTMS was then used to identify unique mass spectrometry (MS) peaks. Sensitivity, specificity, and the area under the receiver operating characteristic (ROC) curve were calculated to measure the test performance of glycan markers. Sixteen unique OS MS signals were identified in ovarian cancer patient sera. Their additive mass/charge intensities were used to determine their presence or absence. The ovarian cancer patients varied in their disease status, with initial cancer stages ranging from IC to IV. Forty-four of 48 patients had detectable OS signals, with CA125 values between 2 and 17,044. Four patients had undetectable signals and their CA125 ranged between 7 and 10. Twenty-three of 24 control subjects had no detectable glycan markers, with CA125 levels between 10 and 64. Sensitivity and specificity values were determined to be 91.6% and 95.8%, respectively. The area under the ROC curve for all 72 samples was 0.954 (95% CI: 0.896, 1.0) using the glycomics assay, which was superior to CA125 in discriminating between cases and controls. This preliminary study suggests that glycomics profiling may be useful for the detection of ovarian cancer. Keywordsbiomarkers; detection; glycomics; mass spectrometry; oligosaccharides; ovarian cancer Ovarian cancer is the most deadly of the gynecological malignancies since the majority of the afflicted patients present with advanced-staged disease. There is a marked difference in the 5-year survival between patients with Stage I-II ovarian cancer (80-95%) compared to Stages III-IV (15-30%)( 1 ). Unfortunately, there are no currently effective strategies for early We recently reported a new glycomics assay to identify abnormal oligosaccharides (OS) present on the glycoproteins of ovarian cancer cell lines and human serum from ovarian cancer patients(4). Glycosylation of protein antigens on cancer cells is markedly different compared to normal cells(5 -7 ). The glycoproteins are not only overexpressed but are aberrantly glycosylated. We have shown that mass spectrometry can be used to detect a unique profile of OS that have been stripped from their underlying glycoproteins in four ovarian cancer cell lines (Caov-3, OVCAR-3, SK-OV-3, and ES-2)( 4 ). These cell lines differentially express various mucins, such as MUC 1 and CA125 (MUC 16). However, all of the ovarian cancer cell lines had similar spectra of oligosaccharides when evaluated by MALDI-FT (matrix-assisted laser desorption/ionization; Fourier transformation) mass spectrometry.A preliminary analysis of human serum samples of 18 ovaria...

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Background: Estrogen and progesterone hormone receptors are expressed in a majority of breast cancers. Therefore they are commonly included to the work-up of metastatic breast tumors in addition to the mammary markers, mammaglobin and GCDFP-15. The sensitivity and specificity of various markers for detecting breast cancer is of some concern. Some breast cancer metastases are negative to ER and PR, while tumors of ovarian or endometrial origin are often positive to ER and PR. Our previous study showed that NY-BR-1 is a better mammary marker demonstrating higher positive rate than GCDFP and mammaglobin, in both primary and metastases breast cancers. The aims of the present study are to further investigate the characteristics of NY-BR-1 in various cancerous tissues: 1) whether NY-BR-1 is positive in ER and PR negative breast cancers, 2) whether NY-BR-1 is negative in ER or PR positive ovarian and endometrial cancers, 3) comparison of the expression profile of NY-BR-1 to ER and PR in lung cancers.Materials and Methods: IHC was performed using NY-BR-1, ER and PR antibodies on tissue arrays including three breast cancer arrays (total 207 cases), an endometrial cancer array (70 cases), an ovarian cancer array (70 cases) and a lung cancer array (70 cases). The arrays were scored as following: 1) NY-BR-1 was scored based on the staining intensity and percentage of positive tumor cells: tissue cores which scored 1 (weak) in 5% of tumor cells or scored 2 or above (moderate to strong) in 1% tumor cells were counted as positive; 2) ER and PR were scored as positive if ≥5% showed immunoreactivity.Results: In a total of 207 breast cancer cases, 38.2% (79 cases) of the cases are negative to ER and 46.9% (97 cases) are negative to PR. Among the total 67 cases of double ER and PR negative breast cancers, 46.3% (31 cases) are NY-BR-1 positive.In the 70 ovarian tumor cases, 25.7% (18 cases) of the cases`express ER, 45.7% (32 cases) express PR and all but one are negative to NY-BR-1. Among ER or PR positive ovarian tumors (37 cases), 97.3% are NY-BR-1 negative.In the 70 cases of endometrial cancers, 27.1% of the cases (19 cases) are positive to ER, 60% (42 cases) are positive to PR and only 3 cases are positive to NY-BR-1. Among those that are either ER or PR positive tumors, 97.8% were NY-BR-1 negative.Out of a total of 70 lung cancer cases none are ER or PR positive. However, 12.9% are NY-BR-1 positive.Discussion: 1) The present study demonstrated that NY-BR-1 is often positive in both ER and PR negative breast cancers; therefore NY-BR-1 could be complementary to ER and PR in the work-up of breast metastases 2) Among the ovarian and endomethrial cancers tested, more than a quarter are positive to ER and about half are positive to PR, while rarely expressing NY-BR-1. Thus, it might be appropriate to use NY-BR-1 and avoid using ER and PR in the detection of breast metastases in the ovary and endometrium. 3) NY-BR-1 expresses in approximately 13% of primary lung cancers while ER and PR are totally negative suggesting that these markers are more specific to mammary origin in lung, whereas, NY-BR-1 should be used with caution. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6018.