Skip to main content

Advertisement

SpringerLink
Log in

A comprehensive salivary analysis for oral cancer diagnosis

  • Original Paper
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

This study utilized comprehensive salivary analysis to evaluate biochemical and immunological parameters in the saliva of oral squamous cell carcinoma (OSCC) patients.

Methods

Whole saliva was collected from 25 otherwise healthy OSCC patients and compared to 25 healthy, age- and gender-matched individuals. All OSCC lesions were located at the lateral aspect of the mobile tongue. The salivary parameters analyzed included: sodium (Na), potassium (K), calcium (Ca), inorganic phosphate (P), magnesium (Mg), total protein (TP), albumin (Alb), lactate dehydrogenase (LDH), amylase (Amy), total immunoglobulin G (IgG), secretory immunoglobulin A (Sec. IgA), epidermal growth factor, insulin growth factor I (IGF-I) and metalloproteinases MMP-2 and MMP-9.

Results

In cancer patients, salivary median total protein concentration was significantly higher by 26% (P = 0.01), as were concentrations of Na, Ca, P and Mg by 14% (P = 0.05), 59% (P = 0.05), 39% (P = 0.08) and 28% (P = 0.12), respectively. Amy and K concentrations were lower by 25% (P = 0.12) and 15% (P = 0.03), respectively. Alb was 108% higher (P = 0.0007), as were salivary LDH (88%, P = 0.002) and total IgG (125%, P = 0.01), while Sec. IgA was lower by 45% (P = 0.001). Concentrations of IGF, MMP-2 and MMP-9 were significantly higher by 117% (P = 0.03), 75% (P = 0.0003) and 35% (P = 0.05), respectively.

Conclusions

Comprehensive salivary analysis revealed an overall altered salivary composition in OSCC, indicating a compromised oral environment in these patients and suggesting salivary analysis as a new diagnostic tool for oral cancer. Local therapeutic agents can be easily applied to the oral mucosa, altering its “bathing medium”–the saliva.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Adams TE, McKern NM, Ward CW (2004) Signalling by the type 1 insulin-like growth factor receptor: interplay with the epidermal growth factor receptor. Growth Factors 22(2):89–95

    Article  PubMed  CAS  Google Scholar 

  • Baum JB, Costa PT, Izutsu TK (1989) Sodium handling by aging human parotid glands is inconsistent with a two-stage secretion model. Amer J Physiol 246:35–39

    Google Scholar 

  • Bayes-Genis A, Conover CA, Schwartz RS (2000) The insulin-like growth factor axis: a review of atherosclerosis and restenosis. Circ Res 86(2):125–130

    PubMed  CAS  Google Scholar 

  • Ben Aryeh H, Jungerman T, Szargel R, Klein E, Laufer D (1996) Salivary flow-rate and composition in schizophrenic patients on clozapine: subjective reports and laboratory data. Biol Psychiatry 39:946–949

    Article  PubMed  CAS  Google Scholar 

  • Fang J, Shing Y, Wiederschain D, Yan L, Butterfield C, Jackson G, Harper J, Tamvakopoulos G, Moses MA (2000) Matrix metalloproteinase-2 is required for the switch to the angiogenic phenotype in a tumor model. Proc Natl Acad Sci USA 97(8):3884–3889

    Article  PubMed  CAS  Google Scholar 

  • Foulstone E, Prince S, Zaccheo O, Burns JL, Harper J, Jacobs C, Church D, Hassan AB (2005) Insulin-like growth factor ligands, receptors, and binding proteins in cancer. J Pathol 205(2):145–153

    Article  PubMed  CAS  Google Scholar 

  • Hardt M, Witkowska HE, Webb S, Thomas LR, Dixon SE, Hall SC, Fisher SJ (2005) Assessing the effects of diurnal variation on the composition of human parotid saliva: quantitative analysis of native peptides using iTRAQ reagents. Anal Chem 77(15):4947–4954

    Article  PubMed  CAS  Google Scholar 

  • Hohenwallner W, Stein W, Hafkenscheid JC, Kruse-Jarres JD, Kaiser C, Hubbuch A, KleinG (1989) Reference ranges for alpha-amylase in serum and urine with 4,6-ethylidene-(G7)-1-4-nitrophenyl-(G1)-alpha,D-maltoheptaoside as substrate. J Clin Chem Clin Biochem 27:97–101

    PubMed  CAS  Google Scholar 

  • Kantola S, Parikka M, Jokinen K, Hyrynkangs K, Soini Y, Alho OP, Salo T (2000) Prognostic factors in tongue cancer—relative importance of demographic, clinical and histopathological factors. Br J Cancer 83:614–619

    Article  PubMed  CAS  Google Scholar 

  • Kuribayashi A, Kataoka K, Kurabayashi T, Miura M (2004) Evidence that basal activity, but not transactivation, of the epidermal growth factor receptor tyrosine kinase is required for insulin-like growth factor I-induced activation of extracellular signal-regulated kinase in oral carcinoma cells. Endocrinology 145(11):4976–4984

    Article  PubMed  CAS  Google Scholar 

  • Liu SY, Lin MH, Yang SC, Huang GC, Chang L, Chang S, Yen CY, Chiang WF, Kuo YY, Chen LL, Lee CH, Liu YC (2005) Increased expression of matrix metalloproteinase-2 in oral cells after short-term stimulation and long-term usage of areca quid. J Formos Med Assoc 104(6):390–397

    PubMed  CAS  Google Scholar 

  • Mancini G, Carbonara AO, Heremans JF (1965) Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry 2:235–254

    Article  PubMed  CAS  Google Scholar 

  • McQuibban GA, Gong JH, Tam EM, McCulloch CA, Clark-Lewis I, Overall CM (2000) Inflammation dampened by gelatinase A cleavage of monocyte chemoattractant protein-3. Science 289(5482):1202–1206

    Article  PubMed  CAS  Google Scholar 

  • Myers JN, Elkins T, Roberts D, Byers RM (2000) Squamous cell carcinoma of the tongue in young adults: increasing incidence and factors that predict treatment outcomes. Otolaryngol Head Neck Surg 122:44–51

    Article  PubMed  CAS  Google Scholar 

  • Nagler RM, Lischinsky S, Diamond E, Klein E, Reznick AZ (2001) New insights into salivary lactate dehydrogenase of human subjects. J Lab Clin Med 137:363–369

    Article  PubMed  CAS  Google Scholar 

  • Nagler RM, Hershkovich O, Lischinsky S, Diamond E, Reznick AZ (2002a) Saliva analysis in the clinical setting: revisiting an underused diagnostic tool. J Investig Med 50(3):214–225

    PubMed  CAS  Google Scholar 

  • Nagler RM, Klein I, Zarzhevsky N, Drigues N, Reznick AZ (2002b) Characterization of the differentiated antioxidant profile of human saliva. Free Radic Biol Med 32:268–277

    Article  PubMed  CAS  Google Scholar 

  • Nagler RM, Bahar G, Shpitzer T, Feinmesser R (2006) Concomitant analysis of salivary tumor markers—a new diagnostic tool for oral cancer. Clin Cancer Res 12(13):3979–3984

    Article  PubMed  CAS  Google Scholar 

  • Pomerantz RG, Grandis JR (2004) The epidermal growth factor receptor signaling network in head and neck carcinogenesis and implications for targeted therapy. Semin Oncol 31(6):734–743

    Article  PubMed  CAS  Google Scholar 

  • Renehan AG, Zwahlen M, Minder C, O’Dwyer ST, Shalet SM, Egger M (2004) Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet 363(9418):1346–1353

    Article  PubMed  CAS  Google Scholar 

  • Reznick AZ, Hershkovich O, Nagler RM (2004) Saliva—a pivotal player in the pathogenesis of oropharyngeal cancer. Br J Cancer 91(1):111–118

    Article  PubMed  CAS  Google Scholar 

  • Ribeiro KC, Kowalski LP, Latorre MR (2000) Impact of comorbidity, symptoms, and patients’ characteristics on the prognosis of oral carcinomas. Arch Otolaryngol Head Neck Surg 126:1079–1085

    PubMed  CAS  Google Scholar 

  • Seiwart TY, Cohen EE (2005) State-of-the-art management of locally advanced head and neck cancer. Br J Cancer 92(8):1341–1348

    Article  Google Scholar 

  • Wu HJ, Chi CW, Liu TY (2005) Effects of pH on nicotine-induced DNA damage and oxidative stress. J Toxicol Environ Health A 68(17–18):1511–1523

    Article  PubMed  CAS  Google Scholar 

  • Zavras AI, Pitiphat W, Wu T, Cartsos V, Segas J, Lefantzis D, Joshipura K, Douglass CW, Diehl SR (2003) Insulin-like growth factor II receptor gene-167 genotype increases the risk of oral squamous cell carcinoma in humans. Cancer Res 63(2):296–297

    PubMed  CAS  Google Scholar 

Download references

Acknowledgment

The authors thank Mrs Gan for her assistance in the preparation of this paper.

Author information

Authors and Affiliations

  1. Department of Otorhinolaryngology, Rabin Medical Center, Petah Tiqva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Thomas Shpitzer, Gideon Bahar & Raphael Feinmesser

  2. Oral and Maxillofacial Surgical Department and Oral Biochemistry Laboratory, Rambam Medical Center and Rappaport Faculty of Medicine, Technion—Israel Institute of Technology, 31096, Haifa, Israel

    Rafael M. Nagler

Authors
  1. Thomas Shpitzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gideon Bahar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Raphael Feinmesser
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rafael M. Nagler
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rafael M. Nagler.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shpitzer, T., Bahar, G., Feinmesser, R. et al. A comprehensive salivary analysis for oral cancer diagnosis. J Cancer Res Clin Oncol 133, 613–617 (2007). https://doi.org/10.1007/s00432-007-0207-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-007-0207-z

Keywords

Search

Navigation