CORRESPONDENCE

RESPONSE: Re: Assessment of Plasma DNA Levels, Allelic Imbalance, and CA 125 as Diagnostic Tests for Cancer

Ie-Ming Shih

Correspondence to: Ie-Ming Shih, M.D., Ph.D., Johns Hopkins University School of Medicine, Department of Pathology, 418 N. Bond St., Rm. B-315, Baltimore, MD 21231 (e-mail: ishih{at}jhmi.edu).

I appreciate the valuable comments from Pisal and Sindos. As indicated in our article (1), the purpose of our study was to provide the evidence that allelic imbalance in tumor-released DNA, as detected by digital single nucleotide polymorphism (SNP) analysis, is a potential tumor-associated marker in blood. Like other newly developed technologies, further evaluation of our technique is required before clinical application. We agree that any innovative technology for cancer screening can be useful only if it can detect cancer at early curable stages. Unfortunately, many cancer patients at this curable stage do not present specific symptoms; as a result, cancer is usually diagnosed late. This scenario is always the case for insidious cancers such as ovarian and pancreatic cancers (2,3). We are currently collecting plasma specimens from asymptomatic patients with ovarian cancer, and it should be noted that collection of such blood samples is by no means a simple task because early ovarian cancers are not frequently encountered. Although ovarian cancer can be incidentally identified in women who are evaluated for other medical reasons or belong to a high-risk group of patients who are regularly followed by imaging studies, these instances are rare. The frustration is not uncommon; it is an experience shared by many researchers who are testing new tumor markers for cancer detection. Accordingly, the validation of innovative cancer detection methods would be greatly facilitated through extensive and efficient collaboration networks among institutions for sharing specimen resources and databases. Advocacy for such networks cannot be overemphasized, despite the U.S. government-sponsored program "Early Detection Research Network" (http://www3.cancer.gov/prevention/cbrg/edrn/) that was initiated in 2000. For future studies, we agree that larger case–control or cohort studies should be performed to address how age, menopausal status, histologic grade, and other clinical parameters affect the allelic ratio in plasma DNA. It is also important to demonstrate the utility of digital SNP analysis in distinguishing malignant versus benign diseases such as endometriosis. This feature is important in the differential diagnosis of benign versus malignant diseases.

REFERENCES

1 Chang HW, Ali SZ, Cho SK, Kurman RJ, Shih IM. Detection of allelic imbalance in ascitic supernatant by digital single nucleotide polymorphism analysis. Clin Cancer Res 2002;8:2580–5.[Abstract/Free Full Text]

2 Paley PJ. Ovarian cancer screening: are we making any progress? Curr Opin Oncol 2001;13:399–402.[CrossRef][Medline]

3 Shih IM, Sokoll LJ, Chan DW. Tumor markers in ovarian cancer. In: Diamandis EP, Fritsche HA, Lilja H, Chan DW, Schwartz MK, editors. Tumor markers physiology, pathobiology, technology and clinical applications. Philadelphia (PA): AACC Press; 2002. p. 239–52.



             
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