Salivary protein factors are elevated in breast cancer patients.

While saliva is a source of easily accessible bodily fluids, there has been little effort to study its value in cancer diagnosis. We hypothesized that certain proteins would be elevated in the saliva of patients with breast cancer. Our study included 49 healthy individuals and 49 breast cancer patients. The levels of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and carcinoembryonic antigen (CEA) in the saliva were measured with enzyme-linked immunosorbent assay (ELISA). We observed that salivary fluid protein levels were significantly elevated in cancer patients as follows: i) VEGF, 3.7±1.6 in cancer versus 2.1±1.2 ng/ml in control (p<0.0001); ii) EGF, 3.7±1.7 versus 2.1±1.3 ng/ml (p<0.0001); and iii) CEA, 83±31 versus 66.1±27.1 ng/ml (p=0.0106). The areas under the receiver operating characteristic (ROC) curve (AUC) were 80, 77 and 65%, respectively. The best prediction was from the combination of salivary VEGF and EGF with a sensitivity of 83%, specificity of 74% and AUC of 84%. We conclude that saliva is a novel avenue for tumor marker research and deserves further studies. Saliva may potentially be useful in supplementing current methods of breast cancer detection.

[1]  J. Folkman Role of angiogenesis in tumor growth and metastasis. , 2002, Seminars in oncology.

[2]  M. Nguyen Angiogenic factors as tumor markers , 2004, Investigational New Drugs.

[3]  C. Streckfus,et al.  The Use of Soluble, Salivary c-erbB-2 for the Detection and Post-operative Follow-up of Breast Cancer in Women: The Results of a Five-year Translational Research Study , 2005, Advances in dental research.

[4]  J. Thigpen,et al.  A Preliminary Study of CA15-3, c-erbB-2, Epidermal Growth Factor Receptor, Cathepsin-D, and p53 in Saliva Among Women with Breast Carcinoma , 2000, Cancer investigation.

[5]  J. Richie,et al.  Elevated levels of an angiogenic peptide, basic fibroblast growth factor, in the urine of patients with a wide spectrum of cancers. , 1994, Journal of the National Cancer Institute.

[6]  W. Dubinsky,et al.  Breast Cancer Related Proteins Are Present in Saliva and Are Modulated Secondary to Ductal Carcinoma In Situ of the Breast , 2008, Cancer investigation.

[7]  M. Navazesh,et al.  Methods for Collecting Saliva , 1993, Annals of the New York Academy of Sciences.

[8]  R. Mesía,et al.  Epidermal growth factor in plasma and saliva of patients with active breast cancer and breast cancer patients in follow-up compared with healthy women , 2004, Breast Cancer Research and Treatment.

[9]  J. Folkman,et al.  Basic fibroblast growth factor secreted by an animal tumor is detectable in urine. , 1993, Cancer research.

[10]  A. Jemal,et al.  Cancer Statistics, 2007 , 2007, CA: a cancer journal for clinicians.

[11]  L. Fletcher,et al.  Vascular endothelial growth factor in normal human salivary glands and saliva: a possible role in the maintenance of mucosal homeostasis. , 1998, Laboratory investigation; a journal of technical methods and pathology.

[12]  H. Mulcahy,et al.  Circulating nucleic acids in plasma and serum as a noninvasive investigation for cancer: Time for large‐scale clinical studies? , 2003, International journal of cancer.

[13]  A Kingman,et al.  The presence of soluble c-erbB-2 in saliva and serum among women with breast carcinoma: a preliminary study. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[14]  Ming Lu,et al.  Nipple Fluid Basic Fibroblast Growth Factor in Patients with Breast Cancer , 2005, Cancer Epidemiology Biomarkers & Prevention.

[15]  E. Kohn,et al.  Proteomic analysis for the early detection and rational treatment of cancer--realistic hope? , 2005, Annals of oncology : official journal of the European Society for Medical Oncology.

[16]  M. Nguyen,et al.  Breast-cancer diagnosis with nipple fluid bFGF , 2000, The Lancet.

[17]  M. Mildner,et al.  Vascular endothelial growth factor is constitutively expressed in normal human salivary glands and is secreted in the saliva of healthy individuals , 1998, The Journal of pathology.

[18]  J. Garst,et al.  Epidermal growth factor receptor inhibitors and their role in non-small-cell lung cancer , 2005, Current oncology reports.

[19]  M S Pepe,et al.  Phases of biomarker development for early detection of cancer. , 2001, Journal of the National Cancer Institute.

[20]  David Elashoff,et al.  Salivary Transcriptome Diagnostics for Oral Cancer Detection , 2004, Clinical Cancer Research.

[21]  R. Bast,et al.  American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  F. Kabbinavar,et al.  Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.