Cancer diagnosis: from dogs to DNA or from DNA to dogs?

Laboratory medicine plays an increasingly important role in the management of cancer patients (1) . The involvement of laboratory medicine in clinical oncology is based on the concept of biomarkers. A biomarker may be defi ned as a parameter that can be detected in the laboratory and is associated with malignant transformation or tumor progression. The utilization of biomarkers encompasses predicting the subject ’ s risk of cancer [e.g., determining BRCA1 mutation to identify individuals with high risk of breast and ovarian cancer (2) ], contributing to the diagnosis [e.g., utilization of tumor markers for pre-operative diagnosis of ovarian cancer (3, 4) ], predicting the prognosis and response to therapy, or monitoring the therapeutic response or detecting the recurrence. Biomarkers are also used to assess the toxicity of anti-cancer therapy (5) . In the current issue of Clinical Chemistry and Laboratory Medicine Lippi and Cervellin (6) present a rather provocative topic that may seem in stark contrast with the prevalent “ conventional ” use of laboratory diagnostics in cancer medicine. The authors summarize the experience with canine olfactory detection of cancer from early anecdotal reports to subsequent prospective studies. The scientifi c foundations of canine olfactory detection are also thoroughly reviewed and the pitfalls of this approach in cancer screening, including the problems already identifi ed, or potential confounding issues yet to be investigated are also addressed. The interest in cancer screening was prompted mainly by dramatic differences in survival rates of patients with malignant tumors according to the stage at diagnosis. Early detection through screening programs has resulted in increased survival of patients with breast cancer, cervical cancer or prostate cancer (7, 8) . In addition, the therapy of advanced tumors is much more expensive compared to tumors detected at an early stage. Thus, early detection markedly increases cost-effectiveness of therapy. Unfortunately, for the malignant tumors of most primary locations an effective screening still remains an unfulfi lled dream. The idea of using dogs for cancer screening may seem odd at fi rst glance and evokes to some readers the specter of alternative medicine. Physicians who have some experience with uses (or rather abuses) of so-called alternative medicine may be alarmed by the perspective of barking of a dog in a doctor ’ s offi ce or clinical laboratory forming the basis of important medical decisions. However, everyone is familiar from daily life with the use of canine olfactory detection to detect explosives or illicit drugs, and the use of canine olfactory detection for security or forensic purposes is a generally accepted practice. The use of dogs is well established in forensic medicine, for example, for searching for human remains (cadaver dogs) (9) or in fi re investigations (10) . Why then should this “ technology ” not be acceptable for diagnosis of today ’ s most dreaded disease ? Frankly speaking, for most tumors we do not have an effective alternative to offer, and it is not ethical to reject a method only because it does not fi t our idea of a screening method. A number of laboratory assays have been established relying on sample interaction with complex organisms (e.g., Limulus amebocyte lysate test that utilized horseshoe crab lysate to detect the presence of endotoxin), so why should we exclude the species Canis familiaris ? The potential of canine olfactory detection in cancer diagnosis could be illustrated by a recent Japanese study in patients with colorectal cancer (11) . Colorectal cancer is one of the leading causes of cancer-related death. When detected early, the cure rate is high, but the curability decreases dramatically with advancing stage. The positive predictive value of fecal occult blood test, the screening method currently in use, is low. Additional studies are needed to clarify positive fi ndings from the screening test, colonoscopy or barium enema, imposing a certain burden both on the patients and the system. The results of the study by Sonoda et al. (11) show that the sensitivity of canine olfactory detection when compared with colonoscopy fi ndings was over 90 % , while the specifi city for stool and breath samples was 99 % . These results may look almost too good to be true. In any case, more investigations of canine olfactory detection for cancer screening are needed, and the method still has a long way to go before it can be used in clinical medicine. The sensitivity, specifi city, reproducibility and the fact of whether the method actually saves lives have to be established. The concept of utilization of canine olfactory detection in the diagnosis of cancer may seem to be in contrast with the utilization of molecular diagnostics in cancer medicine. We can, for example, contrast the study by Sonoda et al. (11) with a study examining the potential of early detection of the same tumor, colorectal cancer, published recently by the same authors who present in the current issue the review on canine olfactory detection of cancer (12) . The authors investigated the potential of measuring cell-free DNA in the sera of patients with colorectal cancer, polyps and normal subjects. Cell-free DNA concentrations were markedly increased in patients with colorectal cancer, and, more importantly, increased cell-free DNA concentrations separated cancer patients from normal subjects much better than the levels of an established