Soluble ErbB3 levels in bone marrow and plasma of men with prostate cancer.

PURPOSE: Prostate cancer tends to metastasize to bone and induce osteoblastic lesions. We identified a soluble form of ErbB3 (sErbB3), p45-sErbB3, in bone marrow supernatant from men with prostate cancer bone metastasis and showed that p45-sErbB3 enhances bone formation. We aimed to understand clinical implications of sErbB3 by establishing an ELISA to detect sErbB3 levels in bone marrow and plasma samples. EXPERIMENTAL DESIGN: We did ELISAs on marrow from 108 men [34 with androgen-dependent disease, 30 with androgen-independent disease (AI) but negative bone scan (AI/BS-), and 44 with AI and positive bone scan (AI/BS+)], sequential marrow from 5 men during treatment, plasma from 52 men before and after docetaxel treatment, and plasma from 95 men ages > or =70 years old without prostate cancer. RESULTS: Some men with clinically detectable bone metastasis had high sErbB3 levels. Within the AI/BS- group, higher sErbB3 levels seemed to yield lower rates of bone metastasis. In the AI/BS+ group, detectable bone metastases took longer to appear in men with higher sErbB3 levels than in men with lower sErbB3 levels (median, 82 versus 41 months). However, high sErbB3 levels did not confer survival benefit after metastasis development. Among men with metastatic progression in bone, docetaxel treatment reduced plasma sErbB3 (P < 0.0001) but did not affect bone-specific alkaline phosphatase (P = 0.206) or prostate-specific antigen (P = 0.906). sErbB3 was also detected in men without prostate cancer. CONCLUSIONS: The apparent correlation between higher sErbB3 levels and longer time to bone metastasis suggests that sErbB3 participates in progression in bone of prostate cancer.

ERCC1 and TS Expression as Prognostic and Predictive Biomarkers in Metastatic Colon Cancer.

In patients with metastatic colon cancer, response to first line chemotherapy is a strong predictor of overall survival (OS). Currently, oncologists lack diagnostic tests to determine which chemotherapy regimen offers the greatest chance for response in an individual patient. Here we present the results of gene expression analysis for two genes, ERCC1 and TS, measured with the commercially available ResponseDX: Colon assay (Response Genetics, Los Angeles, CA) in 41 patients with de novo metastatic colon cancer diagnosed between July 2008 and August 2013 at the University of California, San Diego. In addition ERCC1 and TS expression levels as determined by RNAseq and survival data for patients in TCGA were downloaded from the TCGA data portal. We found that patients with low expression of ERCC1 (n = 33) had significantly longer median OS (36.0 vs. 10.1 mo, HR 0.29, 95% CI .095 to .84, log-rank p = 9.0x10-6) and median time to treatment to failure (TTF) following first line chemotherapy (14.1 vs. 2.4 mo, HR 0.17, 95% CI 0.048 to 0.58, log-rank p = 5.3x10-4) relative to those with high expression (n = 4). After accounting for the covariates age, sex, tumor grade and ECOG performance status in a Cox proportional hazard model the association of low ERCC1 with longer OS (HR 0.18, 95% CI 0.14 to 0.26, p = 0.0448) and TTF (HR 0.16, 95% CI 0.14 to 0.21, p = 0.0053) remained significant. Patients with low TS expression (n = 29) had significantly longer median OS (36.0 vs. 14.8 mo, HR 0.25, 95% CI 0.074 to 0.82, log-rank p = 0.022) relative to those with high expression (n = 12). The combined low expression of ERCC1/TS was predictive of response in patients treated with FOLFOX (40% vs. 91%, RR 2.3, Fisher's exact test p = 0.03, n = 27), but not with FOLFIRI (71% vs. 71%, RR 1.0, Fisher's exact test p = 1, n = 14). Overall, these findings suggest that measurement of ERCC1 and TS expression has potential clinical utility in managing patients with metastatic colorectal cancer.

The central role of osteoblasts in the metastasis of prostate cancer.

Prostate cancer (PCa) is the most common malignancy in men. Although mortality from PCa has been declining over the past decade, metastasis can substantially shorten survival time and remains a major challenge in maintaining quality of life for survivors. PCa cells preferentially metastasize to bone and typically result in osteoblastic lesions. In the late stages of disease, however, osteolytic lesions are observed. The mechanisms of PCa bone metastasis are still unclear, but relationships between the PCa cells and the bone tissue elements are suspected of being more complex than initially thought. Far from being an innocent bystander, the bone participates actively in the metastatic process and provides the cancer cells with growth factors and a fertile environment. Among the various cells in the bone environment, osteoblasts have a central role through their bidirectional interactions with the PCa cells. This review discusses the possible mechanisms of PCa bone metastasis and highlights the essential role of osteoblasts in the metastasis of PCa to bone.

The consanguinity effect on QF-PCR diagnosis of autosomal anomalies.

OBJECTIVES: Quantitative Fluorescent PCR (QF-PCR) is a simpler and faster method of detecting common chromosomal abnormalities when compared to cytogenetic analysis. The aim of our study is to investigate the applicability of this methodology in a population where consanguineous marriages are common and to estimate the heterozygous frequency of the PCR markers used. METHODS: Four hundred and twenty-three DNA samples were extracted from uncultured amniocytes and amplified with 18 short tandem repeats (STR) markers specific to chromosomes 13, 18 and 21. Amplification products were analyzed using the GeneScan software. RESULTS: QF-PCR correctly identified all the numerical abnormalities related to chromosomes 13, 18 and 21. A total of 24 autosomal trisomies (5.7%) were detected. The markers D21S1432 and D21S11 were the most consistent in providing unequivocal positive results for chromosome 21 and the heterozygosity percentages of the markers used were lower than the values reported in Western populations. CONCLUSION: QF-PCR is reliable for the prenatal diagnosis of numerical anomalies of the chromosomes 13, 18 and 21 in our study population. The absence of STR heterozygosity data from Lebanon and surrounding countries makes our study very useful for the development of a reliable QF-PCR trisomy detection test.

Inflammatory breast cancer in a male.

Male breast cancer is very rare, especially inflammatory breast cancer, which is an aggressive, rapidly proliferating manifestation of primary breast carcinoma. We present a case report of a 56-year-old man in Lebanon who died 8 months after being diagnosed with inflammatory breast cancer.