Are there special genetic differences between a benign tumor and metastatic cancer that we could test for?
The short answer is yes, for some cancers. The long, detailed answer follows.
Not all tumors are cause for alarm. Most are benign, that is, they are harmless and disappear naturally. Benign tumors are localized to a specific tissue and do not spread to other parts of the body. In contrast, malignant tumors, or cancers, cause significant tissue damage and can spread to other parts of the body and cause new tumors (metastasis).
Usually, genetic perturbations cause a benign tumor or a normal cell to become malignant. However, the exact same genetic differences do not occur in all such benign-to-malignant transformations. Similar outcomes could be caused by very different genetic alterations. Therefore, it is challenging to create a single genetic test that differentiates between benign and malignant tumors. In addition, the genetic differences they harbor vary depending on the originating tissue and the subtype of cancer. Each cancer subtype has its own distinct genetic profile, and scientists have been trying to identify diagnostic markers for particular malignant tumors. They have been successful in some cases. For instance, oncologists are able to differentiate between malignant and benign gastrointestinal tumors by using the gene c-kit as a molecular marker (1). However, such cancer-specific genetic or molecular markers have not yet been identified for many types of cancers.
If genetic markers are hard to find, how does a doctor determine whether a tumor is benign or malignant? Rather than using genetic markers, doctors resort to microscopy to look at tumor architecture. The analysis begins by performing a biopsy, that is, taking out a very small piece of the suspected tissue from the body. During normal circumstances, under a microscope, the cells look ordered and the tissue is surrounded by a basement membrane (see figure). By looking at the degree of change from normal tissue, a pathologist can determine the severity of the tumor. A metastatic tumor would have ruptured through the basement membrane, and the cells have different characteristics (morphology) under the microscope than normal ones or even benign tumors.
Although benign tumors appear different than normal cells because of increased proliferation, their tissue architecture remains intact and the cells have not spread beyond the tumor site. If cells from a tumor site are found in other parts of the body, it provides additional strong evidence that the tumor is metastatic. All these factors allow a doctor to determine whether a tumor is benign or malignant.
Why do we need genetic tests if we can differentiate between tumors using a biopsy? Although it is easy to differentiate a highly metastatic tumor from a benign tumor, we do not know whether a benign tumor will later develop into a metastatic tumor. As mentioned previously, most benign tumors, such as colon polyps or pancreatic cysts, disappear naturally. But additional tests are needed to determine whether these tumors could pose a risk to the patient later and to avoid doing an unnecessary invasive surgery to remove them. Genetic tests provide an early diagnostic tool to address these problems. For example, in pancreatic tumors, testing for KRAS and GNAS gene mutations helps identify potential metastatic tumors from the innumerable benign ones (2).
New genetic differences between benign and malignant tumors are being discovered every day. Yet, it is still challenging to create a single genetic test that differentiates between them. Currently, a combination of histopathological, genetic, molecular, and physiological tests is used to determine tumor type and to differentiate between a benign and a malignant tumor.
A simplified illustration of the cellular architecture in normal tissues, and benign and malignant tumors. Note that in malignant tumors the basement membrane is compromised and a change in cellular morphology occurs.
1. Lasota et al. 1999. Mutations in exon 11 of c-Kit occur preferentially in malignant versus benign gastrointestinal stromal tumors and do not occur in leiomyomas or leiomyosarcomas. Am. J. Pathol. 154(1):53–60, http://www.ncbi.nlm.nih.gov/pubmed/9916918
2. Wu et al. 2011. Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development. Sci. Transl. Med. 3(92):92, http://stm.sciencemag.org/content/3/92/92ra66
WebMD: Benign Tumors
BBC: Lumps and bumps
wiki: Cancer staging