Papillary Renal Cell Carcinoma – An Introduction
In the US, there are more than 60,000 new cases of renal cell carcinoma (rcc) each year, the vast majority, about 75%, of which are clear cell histology (ccrcc). Papillary renal cell carcinoma (prcc) accounts for 10-15% of the total, or 6-9,000 new cases a year. The histology of the tumor is classified by a pathologist according to what is observed under a microscope. For example, ccrcc cells look clear to the eye, distinguishing them from other kidney cancer types. In prcc, pathologists have established that there are currently two types of distinct diseases, naming them Type 1 and Type 2 (see sample slides below).
In a very small number of cases, prcc can be hereditary. Researchers have found that, for each type, a different specific gene has a mutation in hereditary or familial prcc. For Type 1 it’s the c-Met gene and for Type 2 it’s the FH (fumarate hydratase ) gene. But these mutations occur in fewer than 10% of the prcc cases that are not familial, thus implying that there are other genes involved in the pathogenesis of non-familial, or sporadic prcc. The c-Met gene controls cell growth and proliferation and plays a role in many cancers besides prcc, notably lung, gastric, and melanoma.
In general, prcc is more often localized in the kidney, slower growing, and non-metastatic in comparison to ccrcc, although Type 2 prcc is often aggressive. Some pathologists postulate that there are two categories of Type 2 prcc, one generating indolent tumors, and the second presenting very aggressive tumors with poor survival rates.
In a recent study by the National Cancer Institute, African-Americans who contracted kidney cancer were less likely to have clear cell but were three times as likely to have papillary than Caucasians. This may be related to the sickle-cell genetic disorder, however, there have been no studies that verify this association.
Understanding which gene or genes are mutated in a specific cancer is important since therapy is often guided by that knowledge. For clear cell disease, the VHL gene is mutated or otherwise disabled, giving rise to a biologic process called angiogenesis, or the creation and proliferation of blood vessels that feed a fast growing tumor. So, for clear cell, a number of therapies have been developed by the drug companies to slow or halt angiogenesis in the hope of slowing or stopping the growth of metastasized disease. These so-called targeted therapies were all developed to fight ccrcc, and have been somewhat effective in slowing its progression. They have been less effective when used in prcc patients. Of the eight kidney cancer therapies that have been approved for use by the U.S. Food and Drug Administration (FDA), seven of them were developed to stem angiogenesis and, in the case of two of them, both angiogenesis and cell growth factors. The eighth therapy is Interleukin-2, an immunotherapy that is not at all effective in treating prcc patients.
To summarize, there are no kidney cancer therapies that have been developed specifically to combat prcc, and there are presently few in development by the pharmaceutical companies. Not only is there little clinical research (drug development) being done for prcc, there is a lack of basic research as well. Without research, there is no drug development, and without drugs specific to the disease, metastatic papillary patients have a poor prognosis for survival, especially as compared to ccrcc patients.
The National Cancer Institute is addressing the lack of therapies for prcc by sponsoring a number of clinical trials for this disease, in addition to the basic research that they are continuing with. To assist the NCI’s program, Action to Cure Kidney Cancer has committed a grant of $60,000 this year to fund a full-time prcc researcher at the NCI.
If you are a prcc survivor or caregiver and can help us advocate for the development of drugs specific to papillary disease of all types and help inform prcc patients about their disease, then sign up here to join the effort.
Note: The above slides were provided to us by Ximing J. Yang, MD, PhD, Northwestern University, Feinberg School of Medicine.