Molecular Urinalysis: Applying New Techniques for the Early Diagnosis of Renal Cancer
February 1, 2000 4 minutes read
Molecular Urinalysis: Applying New Techniques for the Early Diagnosis of Renal Cancer
ABSTRACT & COMMENTARY
Synopsis: Twenty-five patients with renal malignancies considered preoperatively to be organ-confined and without metastatic involvement were examined for the presence of urine and serum cancer-specific DNA alterations. Of these, 76% had specific abnormalities in their urine and 60% in the serum. Serum and urine samples obtained from controls (8 patients with nephrolithiasis and 8 normal volunteers) were consistently negative in both urine and serum. The technique may become a useful tool for the early detection of renal cancer, but further study is needed.
Source: Eisenberger CF, et al. J Natl Cancer Inst 1999;91:2028-2032.
The treatment of renal carcinoma continues to be a frustration for medical and radiation oncologists and radical nephrectomy remains the only treatment that produces meaningful survival advantage. However, for patients with disease that has extended beyond the kidney, surgical cure rates are low. Thus, until effective therapies are developed to treat residual disease, efforts at early diagnosis (i.e., detection of tumor confined to the kidney) are warranted.
In this regard, Eisenberger and colleagues report a non-invasive molecular technique for renal cancer detection. They collected matched urine and serum samples from 30 patients with clinically-confined solid renal masses (25 with malignant tumors and 5 with tumors of low malignant potential). Samples were prepared for PCR detection of DNA microsatellites and other cancer-specific DNA alterations (loss of heterozygosity [LOH]).
Of the 25 patients with malignant renal tumors, 19 (76%) were found to have one or more DNA alterations in their urine specimen and 15 (60%) were found to have alterations in their serum by microsatellite analysis. In every case, the microsatellite changes in the urine and serum were identical to those found to be existent in the primary tumor. Three of five patients with tumors of low malignant potential were found to have DNA alterations in the urine, but none were found in the serum.
A similar analysis was performed on the serum and urine from eight patients with nephrolithiasis and from eight normal controls. In none of these 16 individuals were DNA alterations detected.
Eisenberger et al suggest that microsatellite DNA analysis of urine specimens may be a valuable tool for the early detection of surgically curable renal cancer.
COMMENT by William B. Ershler, MD
The concept of early detection resulting in higher cure rates is theoretically sound. An ideal method is one that is non invasive, inexpensive, and effective at detecting tumor at a curable stage.1 The molecular techniques described are clearly a step in this direction, although it remains to be seen that they will be useful clinically.
The method is clearly non invasive and with new high through-put PCR technology being developed, it is also likely to become inexpensive.2 However, the question of efficacy remains. Renal cancer has a propensity to spread early, primarily by hematogenous routes. This study supports that notion; 60% of patients assessed preoperatively to have organ-confined disease were found to have cancer-specific DNA alterations in their serum. Only a slightly higher percentage (76%) had the DNA alterations in their urine. Whereas it is likely the analysis is both specific and sensitive, it may be that it detects disease at too late a stage. Presence of cancer-specific DNA in the serum strongly suggests the presence of circulating neoplastic cells and, thus, at least the early stage of the metastatic process (invasion and embolization) is likely to have occurred. Accordingly, it will be important to further investigate this as it may turn out that the test will be more useful as a prognostic indicator than a screening tool. For example, patients with locally-confined lesions with serum-detected DNA alterations may fall into a category of patients likely to recur with distant metastases. In contrast, the 40% with similar lesions, but serum-negative, might be those that were cured by nephrectomy.
If the technique is to be applied as a screen, it is likely that those individuals with DNA alterations detected in the urine, but not in the serum, will be those that truly benefit from early detection.
Whether molecular urinalysis turns out to be an effective screening tool remains to be determined. However, this does not detract from the importance of these analyses as we attempt to learn more about the biology of this otherwise treatment-refractory disease.
References
1. Fahs MC, et al. Ann Int Med 1992;117:520-527.
2. Mao L, et al. Science 1996;271:659-662.
Which of the following statements about the detection of cancer specific DNA alterations in
the serum and/or urine of patients with a known renal mass is true?a. DNA alterations in the serum were found only in patients with known metastatic involvement at other sites.
b. DNA alterations present in the urine but not in the serum are indicative of local disease, without metastases.
c. DNA alterations in the serum and urine are present in a majority of patients preoperatively thought to have organ-confined disease.
d. The data now support this technique as an established method of screening for renal cancer.
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