Salivary biomarkers for the detection of malignant tumors that are remote from the oral cavity.

Proteomic analyses by mass spectrometry are propelling the field of medical diagnostics forward at unprecedented rates because of its ability reliably to identify proteins that are at the femtomole level in concentration. These advancements have also benefited biomarker research to the point where saliva is now recognized as an excellent diagnostic medium for the detection of malignant tumors that are remote from the oral cavity. Saliva is easy to collect and may provide diagnostic information about a variety of cancers. In particular, proof-of-principle has been demonstrated for salivary biomarker research. This article reviews the literature, discusses the theories associated with saliva-based tumor diagnostics, and presents the current research focused on the use of saliva as a diagnostic medium for the detection of cancer.

The use of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to detect putative breast cancer markers in saliva: a feasibility study.

BACKGROUND: Technologies are now available enabling saliva to be used to diagnose disease, predict disease progression, and monitor therapeutic efficacy. This pilot study describes the use of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI) to detect putative breast cancer markers in saliva. METHODS: Salivary specimens were analyzed as either pooled cancer saliva specimens, or individual specimens from healthy women and women diagnosed with carcinoma of the breast. The specimens were applied to a variety of protein chip arrays, washed extensively to remove unbound analytes and analyzed on a SELDI mass spectrometer. RESULTS: The results of this initial study suggest that the WCX protein chip array prepared and washed at pH 3.5 yielded the most promising results. Additionally, the analyses revealed a number of proteins that were higher in intensity among the cancer subjects when compared with controls. These salivary proteins were present at the 18, 113, 170, 228 and 287 km/z ranges using SELDI analyses. CONCLUSIONS: The study suggests that saliva may be useful for high-throughput biomarker discovery.

The potential use of saliva to detect recurrence of disease in women with breast carcinoma.

BACKGROUND: Approximately 1 woman in every 10 will develop breast cancer in her lifetime. It has been shown that screening for breast cancer can reduce breast cancer mortality. The use of a saliva-based test could prove to be very useful in post-operative and/or adjunctive therapy management of breast cancer patients. METHODS: The following study was undertaken to establish the possible usefulness of the salivary protein product of the oncogene c-erbB-2 in following patients diagnosed with carcinoma of the breast. Included in this study were 25 patients with a mean age of 54 years with varying histological diagnoses and stages of carcinoma of the breast. ELISA assays for c-erbB-2 and CA 15-3 were performed on serum and stimulated whole saliva samples collected on all patients prior to any adjunct therapy or surgery and sequentially during therapy. RESULTS: The results of the GLM analyses using marker concentration as the dependent variable and treatment regimen and the serial assessments as independent variables yielded a significant overall model for both the serum (P < 0.007) and salivary (P < 0.017) c-erbB-2 markers. The model for serum c-erbB-2, however, exhibited a significant difference for treatment regimen (P < 0.001) with the chemotherapy and radiation treatment regimen being significantly different (P < 0.001) from the other treatment therapies. Time (serial assessments) was not significant. The model for the salivary c-erbB-2 marker was reversed. Treatment regimen was not significant for this model; however, time (serial assessments) was significant (P < 0.002). The serum and salivary CA 15-3 marker models yielded no significant results. Paired t-test analyses indicated that only the salivary c-erbB-2 concentrations exhibited a significant difference between the pre- and post-therapy values (t = 4.245, P < 0.0001). Additionally, salivary c-erbB-2 displayed greater percent reductions across all therapies as compared to the other markers. CONCLUSIONS: This preliminary study appears to indicate that c-erbB-2 protein expression in saliva may be a very useful diagnostic tool for measuring patient response to chemotherapy and/or surgical treatment of their disease.