Biopharmaceutical Cancer Genomics

The bladder is a hollow organ in the lower abdomen
(pelvis). It collects and stores urine produced by the kidneys.

• As it fills with urine, the muscular wall of the
  bladder stretches and the bladder gets larger.
  
  
  
• When the bladder reaches its capacity of urine, the
  bladder wall contracts, although adults have voluntary control over the timing
  of this contraction. At the same time, a urinary control muscle (sphincter) in the urethra relaxes. The
  urine is then expelled from the bladder.
  
  
  
  
• The urine flows through a narrow tube called the urethra and leaves the body. This process is called urination, or micturition.

Cancer occurs when normal cells undergo a transformation whereby they grow and multiply without normal controls.

• As the cells multiply, they form an area of abnormal
  cells. Medical professionals call this a tumor.
  
  
  
• As more and more cells are produced, the tumor
  increases in size.
  
  
  
• Tumors overwhelm surrounding tissues by invading
  their space and taking the oxygen and nutrients they need to survive and
  function.
  
  
  
• Tumors are cancerous only if they are malignant. This
  means that, because of their uncontrolled growth, they encroach on and invade
  neighboring tissues.
  
  
  
  
• Malignant tumors may also travel to remote organs via the bloodstream or the lymphatic system.
  
  
  
• This process of invading and spreading to other organs is called metastasis. Bladder
  cancers are most likely to spread to neighboring organs and lymph nodes prior
  to spreading through the blood stream to the lungs, liver, bones, or other organs.

Of the different types of cells that form the bladder,
the cells lining the inside of the bladder wall are most likely to develop
cancer. Any of three different cell types can become cancerous. The resulting cancers are named after the cell types.

• Urothelial carcinoma (transitional cell carcinoma): This is by far the most common type of bladder cancer in the
  United States. The so-called transitional cells are normal cells that form the
  innermost lining of the bladder wall. In transitional cell carcinoma, these
  normal lining cells undergo changes that lead to the uncontrolled cell growth
  characteristic of cancer.
  
  
  
  
• Squamous cell carcinoma: These cancers originate from the thin, flat cells that typically form as a result of
  bladder inflammation
  or irritation that has taken place for many months or years.
  
  
  
• Adenocarcinoma: These
  cancers form from cells that make up glands. Glands are specialized structures
  that produce and release fluids such as mucus.
  
  
  
• In the United States, urothelial carcinomas account for more than 90% of all bladder cancers. Squamous cell carcinomas make up 3%-8%, and adenocarcinomas make up 1%-2%.

Only transitional cells normally line the rest of the urinary tract. The
kidneys, the ureters (narrow tubes that carry urine from the kidneys to the bladder), the bladder, and the urethra are lined with these cells.

• However, these three types of cancer can develop
  anywhere in the urinary tract.
  
  
  
• If abnormal cells are found anywhere in the urinary
  tract, a search for other areas of abnormal cells is warranted. For example,
  if cancerous cells are found in the bladder, an evaluation of the kidneys and
  ureters is essential.

Bladder cancers are classified (staged) by how deeply
they invade into the bladder wall, which has several layers. Many physicians
subdivide bladder cancer into superficial and invasive disease. Superficial bladder cancer is limited to the innermost linings of the bladder (known as the mucosa and lamina propria). Invasive bladder cancer has at least penetrated the muscular layer of the bladder wall.

• Nearly all adenocarcinomas and squamous cell
  carcinomas are invasive. Thus, by the time these cancers are detected, they
  have usually already invaded the bladder wall.
  
  
  
• Many urothelial cell carcinomas are not invasive. This means that they go no deeper than the superficial layer (mucosa) of the bladder.
  

In addition to stage (how deep the cancer penetrates in the bladder wall), the grade of the bladder cancer provides important information and can help guide treatment. The tumor grade is based on the degree of abnormality observed in a microscopic evaluation of the tumor. Cells from a high-grade cancer have more changes in form and have a greater degree of abnormality when viewed microscopically than do cells from a low-grade tumor. This information is provided by the pathologist, a
physician trained in the science of tissue diagnosis.

• Low-grade tumors are less aggressive.
  
  
  
• High-grade tumors are more dangerous and have a propensity to become invasive.

Papillary tumors are urothelial carcinomas that grow narrow, finger-like projections.

• Benign (noncancerous)
  papillary tumors (papillomas) grow projections out into the hollow part of the
  bladder. These can be easily removed, but they sometimes grow back.
  
  
  
• These tumors vary greatly in their potential to come back (recur). Some types
  rarely recur after treatment; other types are very likely to do so.
  
  
  
  
• Papillary tumors also vary greatly in their potential to be malignant (invasive). A small percentage (15%) do invade the bladder wall. Some invasive papillary tumors grow projections both into the bladder wall and into the hollow part of the bladder.

In addition to papillary tumors, bladder cancer can develop in the form of a flat, red (erythematous) patch on the mucosal surface. This is called carcinoma-in-situ (CIS).

• Although these tumors are superficial, they are high-grade and have a high risk for becoming invasive.

Of all types of cancer, bladder cancer has an unusually high propensity for recurring after treatment. Bladder cancer has a recurrence rate of 50%-80%. The recurring cancer is usually, but not always, of the same type as the first (primary) cancer. It may be in the bladder or in another part of the urinary tract (kidneys or ureters).

Bladder cancer is most common in industrialized countries. It is the fifth most common type of cancer in the United States-the fourth most common in men and the ninth in women.