Vol. 18 • Issue 10
• Page 34
The prognostic differences between the patient identified as having pre-cancerous cells and the patient whose cancer isn't caught until it's metastasized are drastic-often the difference between life and death. New developments in diagnostic tools continue to focus on ways to identify cancerous cells earlier, allowing quick action before the disease has spread too much to control.
Cancer treatment is most effective when an early, precise diagnosis is involved. As both cancer diagnostics and therapies continue to evolve, perhaps the most important developmental focus to build upon is screening and making diagnoses as early as possible. Of course, when screening or risk stratification comes into play, talks move to the need to keep techniques within a reasonable price range.
Rebecca Richards-Kortum, PhD, Stanley C. Moore Professor of Bioengineering at Rice University, expresses the urgent need for finding cost-effective ways to improve early detection succinctly: "We know that detecting cancer before metastasis begins dramatically improves the odds of survival; when detected late, cancer treatment is less effective, has greater morbidity and is more expensive. While improvements in early detection have helped reduce cancer mortality, the full potential of early detection has yet to be realized. At a time when the global incidence of cancer is rapidly increasing and 47 million Americans lack health insurance, there is an urgent need for effective and affordable tools to facilitate early detection and management of cancer."
Integrated Efforts
Collaboration between pathologists and radiologists to speed up the process of precise diagnosis is one concept being explored. New in vivo screening tools that begin the testing cascade for cancer identification are coming to light with hopes of catching cancer or pre-cancerous cells earlier (e.g., the handheld, battery-powered light used to illuminate oral mucosa while a dentist uses filtered eyeglasses to identify changes or the optical biopsy system that shines laser light onto tissue to emit a returning fluorescent signal then measured by a software algorithm to determine whether a biopsy is necessary).
A level of teamwork for optimal identification of cancer is a clear need between radiology and pathology departments-even if only in the sense of improved communications to ensure that preliminary findings from the imaging side of things are verified by pathology.
Troubles With Unknown Primary
One of the most frustrating patient situations encountered is the diagnosis of cancer of unknown or uncertain primary (CUP) for metastatic cancer patients. Identifying the source of an individual's cancer has obvious clinical utility when it comes to treatment, not to mention a patient's peace of mind.
CUP is a biopsy-proven cancer without an identifiable primary tumor, manifesting as a heterogeneous group of malignancies, explains Mark Erlander, PhD, chief scientific officer, bioTheranostics.
CUP constitutes 3-5 percent of all cancer diagnoses in the U.S. each year and is the fourth most common cause of cancer death.
Standard protocols for treating patients with CUP exist, but there's a varied patient outcome and response to treatment, notes Ron Turnicky, DO, practicing pathologist at Monongalia Hospital, Morgantown, WV. Identifying the tumor origin for CUP allows clinicians to take a step toward personalized medicine by providing a more specific chemotherapeutic and targeted (e.g., EGFR inhibitors) treatments, rather than using broad-based medicine and potentially missing the target.
When immunohistochemistry (IHC) fails, tests for identifying the tumor origin for CUP rely on gene expression profiles, comparing the cancer genes to a database in a standardized fashion. This method also eliminates clinical bias that may be present in traditional diagnostic routes.
"The IHC workup is usually driven by information from the clinical presentation and the patient's history," Xiao-Jun Ma, PhD, vice president of R&D and biostatistics at bioTheranostics, emphasizes. "If there's a suspicion of lung cancer, IHC is performed looking for those markers-there's a large degree of bias from the start." But in gene expression profiling for CUP, the pathologist can look at all of the genes in the test's database simultaneously.
"It's the pattern that's discriminating," Dr. Ma continues. "It's more robust than looking at single gene measurement."
Make Room for Markers
Biomarker discovery remains a crucial research need, as biomarkers can help identify whether a suspicious mass is cancerous or noncancerous, ensuring that patients get the treatment they need-and avoiding unnecessary treatment for patients who don't need it. Biomarkers increase sensitivity and specificity for screening, estimating risk and monitoring response to therapies.
Combinations of biomarkers can work together to provide even more precise information and use of biomarkers for diagnosis and monitoring will have a growing role to play in the clinical lab. Cancer antigen-125 (CA125), for example, has been the standard for biomarkers in monitoring ovarian cancer, but 20 percent of women with ovarian cancer do not show increased levels, and CA125 measurements can be affected by other reproductive disorders and will also be elevated during the first trimester of pregnancy.1Recent research, however, has shown that another novel diagnostic marker, human epididymal protein 4 (HE4) can be used in combination with CA125 to more accurately differentiate between benign pelvic masses and ovarian malignancies.2
A Changing Field
As diagnostic techniques change and advance, so too might the systems used to classify cancer, Dr. Turnicky predicts. We've seen this in hematologic pathology, where leukemias have moved toward a molecular classification, and "there's a high probability that we need a new classification system for tumors. Many gastric adenocarcinomas look alike and are classified as being the same," he notes as an example, "but they're probably not the same and there are different responses to various therapies by tumors that look alike."
IHC still has a role to play. "There's this concept that someday there will be a microarray where you put the tumor type in and it'll pop out a molecular answer," Dr. Turnicky acknowledges. "I don't feel that way. I think it'll be an integration that heavily relies on molecular, which will provide prognostic indicators for the patient, but for a long time we'll still be relying on morphology and IHC, then FISH profiling, then more advanced molecular profiling."
Kelly J. Graham is associate editor.
References
1. Ovarian Cancer. Johns Hopkins Department of Pathology. http://www.ovariancancer.jhmi.edu/ca125qa.cfm. Last accessed Sept. 27, 2009.
2. Moore RG, et al. Utility of a novel serum tumor biomarker HE4 in patients with endometrioid adenocarcinoma of the uterus. Gynecologic Oncology 2008. 110;2:196-201.
|