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Unusual
Forms of Prostate Cancer
March 2, 2009
Prostate cancer is one of the most variable human cancers. The
standard prostate cancer is an adenocarcinoma that spreads in
a predictable fashion from the prostate gland to the lymph nodes
in the pelvis, and eventually to bone. Additionally, standard
prostate cancer makes a series of proteins, such as prostate
specific antigen, prostatic acid phosphatase, and prostate specific
membrane antigen. As Dr. Myers has discussed in earlier issues
of Prostate Forum, large variations occur in the speed at which
different cancers grow and spread (even with standard prostate
cancer). Dr. Myers has also discussed how Gleason grade, PSA
doubling time and other tools help us anticipate how dangerous
a man’s cancer is and how aggressive his treatment needs
to be. However, any clinic that sees a large number of prostate
cancer patients will encounter cases that deviate from the well-established
behavior of the common adenocarcinoma of the prostate gland.
There is a distinct subset of men who present with prostate cancer
that is initially limited to the pelvis and that remains limited
to this site despite aggressive use of hormonal therapy. Even
when these cancers become hormone-refractory, they remain limited
to the pelvis. While chemotherapy may initially prove effective,
these cancers eventually become refractory to available drugs.
At some point along the way, the cancer in the pelvis enlarges
to the point that it blocks the flow of urine out of the bladder
or blocks the rectum or adjacent sigmoid colon. Many of these
patients require diversion of either the ureters or colon to
the skin because of this blockade. Because these cancers do not
readily spread to bone, the cancer can become quite extensive
without threatening life.
In 2004, Dr. Logothetis and his colleagues at MD Anderson did
a superb job characterizing a series of these cases. In addition
to describing the clinical details of this form of prostate cancer,
they examined the molecular changes that might account for this
unusual behavior. These cancers did not express certain proteins
characteristic of aggressive metastatic disease. The cancers
that are locally extensive without metastases do not make these
metalloproteinases. For example, matrix metalloproteinases are
proteins that allow the cancer to digest through tissue barriers
to metastatic spread.
As Dr. Myers discusses later in this issue of Prostate Forum,
prostate cancer cells can make proteins normally found in nerve
tissue that are called neuroendocrine markers and this tends
to correlate with the early development of metastatic disease
and hormone-resistance. These localized cancers did not make
any neuroendocrine markers. In normal prostate epithelia cells,
the cells line the prostate gland and ducts. These cells are
stuck together by two molecules that act like Velcro, causing
adjacent cells to adhere to one another: Ecadherin and beta-catenin.
These cancers produced a lot of both components of this Velcro-like
material and that may explain why these cancers have such a difficult
time spreading to bone and other sites; the cancer cells are
glued together and therefore cannot escape into the blood stream.
Read the entire article in Volume
10 Issue 9 of Prostate Forum.
Click here to download this issue now. |
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