Sarah+Thomas


 * John Thomas and Basal Cell Carcinoma**

John Thomas was an avid golfer, spending multiple hours outside playing golf whenever he got the chance. By the time he was a senior in high school, he had won fifty medals and trophies for his accomplishments on the course. When asked what he wanted to do with his life, John would easily respond that he wanted to be a golfer, or work in finances. Other hobbies of his included fly-fishing, playing rugby with friends, gardening and running marathons. If you ever needed to find John, all you would have to do is look outside. At the age of 40, John noticed a rough patch of skin on his upper lip that looked like a sore, but it would not heal. Not alarmed, he nonetheless went to the dermatologist to get it looked at. Agreeing with John, the dermatologist believed it to be a sore and simply burned off the patch of skin. However, when the rough patch returned, John knew that something was amiss. He went to the dermatologist again and after the biopsy, it was confirmed that he had basal cell carcinoma.

There are many types of skin cancer including, squamous cell, melanoma, and basal cell. Squamous cell cancer is found in the top layer of skin and can be easily treated with early detection. Melanoma skin cancer starts in the melanocytes, which are the cells that produce the skin’s color. One of the more serious forms of skin cancer, melanoma is more aggressive and can metastasize to other parts of the body when not detected early on. Basal cell carcinoma, otherwise known as BCC, is a type of skin cancer that develops in the basal cell layer of the skin. Basal cell carcinoma is not an aggressive type of cancer, but it is extremely common in people diagnosed with skin cancer. “According to the American Cancer Society, basal cell carcinomas are the most common type of skin cancer, and approximately eight out of every ten non-melanoma skin cancers will be basal cell carcinoma.”. Millions of people are diagnosed with BCC each year, and a huge percentage of these cases are due to damage caused by too much exposure to the harsh ultraviolet rays from the sun. The vitamin D commonly gained from sun exposure is vital for people to live healthy lifestyles, but it can come at a price if too much time is spent in the sun. John was unfortunate enough to have to pay this price.

John was surprised with his diagnosis due to the fact that no other family members had any form of skin cancer. However, when looking at the type of lifestyle he lived as a child and teenager, it was clear that the numerous hours enjoyed in the relentless sun would lead to his cancer. Other risk factors that played a role in his development of skin cancer include, “light-colored or freckled skin, blue or green eyes, blond or red hair, and many moles”. With having fair skin, blue eyes, and blond hair, John Thomas was a perfect candidate for skin cancer.

**The Molecular Side of BCC**

After John Thomas received the news that he had basal cell carcinoma, questions flooded into his head. If only he had paid attention in his high school biology class. As a finance major, John did not have a clue what was really going on inside his body. Thankfully, with the help from the doctors as well as the Internet, John was able to find out more about this prevalent cancer.

Despite the vast number of cases of basal cell carcinoma, there is not a lot of information about the cause and development of this cancer. “The current model for BCC pathogenesis maintains that UV radiation causes DNA damage in exposed cells”. Basal cell carcinoma is so prevalent because many people are constantly exposed to the sun throughout their lives; this exposure to UV radiation is then harmful to the cell’s genetic information. If the DNA damage is left unrepaired or the cell does not undergo cell death, it is most likely that mutations will occur and accumulate over time. These mutations are dangerous because they allow cancer cells to grow and divide uncontrollably, avoid growth suppressors, and resist cell death – the top three hallmarks of cancer.

Some of the mutations caused by the damage from the sun are loss of function mutations. This means that the tumor suppressor genes can no longer stop the growth of cells. “A loss of function mutation in TP53 has also frequently been associated with BCC as well as many other cancers. TP53 encodes the protein p53, an established tumor suppressor”. TP53 is responsible for sensing the damaged DNA and signals for the cell cycle to stop in order to repair the DNA sequence. If the damage is beyond repair, TP53 will induce apoptosis – programmed cell death. In basal cell carcinoma, a mutation occurs in this gene, and the p53 protein is no longer able to stop the cell cycle. Figuratively speaking, the breaks are cut and there is no stopping the replication of damaged DNA. This results in damaged DNA being replicated into other cells, and then these cells do not properly grow and replicate. It is a downward spiral that cannot be reversed once a mutation occurs in TP53. This accumulation of mutations in the genetic sequence in multiple cells will most likely lead to cancer formation – in John’s case, basal cell carcinoma.

Another common cause for basal cell carcinoma is mutations found in the Sonic Hedgehog signaling pathway. Sonic hedgehog is a protein that is encoded by the sonic hedgehog gene, SSH. In normal cells, “The SHH pathway plays a crucial role in patterning and organogenesis during early development, but is largely inactive in adults, except for its function in tissue repair and maintenance”. However, mutations in this protein are dangerous and thus lead to development of cancers such as basal cell carcinoma. “The genetic alteration of the SHH pathway is detected in about 70% of BCCs”. Similarly to p53, it is another loss of function mutation in PTCH that leads to basal cell carcinoma. “Mutations in the receptor of SHH, the patched gene (PTCH), have been characterized in sporadic BCCs”. In a normal cell, sonic hedgehog is not bound to PTCH, so PTCH limits the release of another protein called smoothened, which is encoded by the SMO gene. SMO can act as an oncogene and lead to unregulated cell growth and division when over activated. In basal cell carcinoma, a mutation occurs in PTCH and sonic hedgehog proteins bind to it, so smoothened is released into the cell membrane. This activation of SMO results in the dissociation of Gli from the inhibitor SUFU (6). “Human Gli1 encodes a transcription activator involved in development that is a known oncogene”. Gli is able to enter the cell’s nucleus and turn on target genes, many which code for cell proliferation and survival. In basal cell carcinoma, the activation of SMO leads increased levels of Gli and then the transcription of genes that lead to the major hallmarks of cancer.

Overall, the loss of function mutations in TP53 and the sonic hedgehog pathway are major causes for basal cell carcinoma. The signaling pathways are very complicated and even one single error can lead to the disruption of the entire system. The constant cell proliferation and ability to survive apoptosis, allows for the tumor to grow and slowly destroy more cells in its path.

**The Treatment**

Despite the terrible news from the dermatologist, John was informed that the survival rate of individuals with BCC was extremely high. Being a husband and father to two children, some of the weight instantly lifted off his shoulders. It is very rare for basal cell skin cancer to spread and metastasis, making it easier for surgeons to locate and remove all the cancerous cells. Almost all individuals with basal cell carcinoma go through surgery in order to remove their cancer. There are different types of surgery based on the severity of the cancer, how large the cancer is, and where it is located on the body.

One of the popular types of surgery is microscopically controlled surgery, also known as Mohs. “Mohs surgery is sometimes used when there is a high risk the skin cancer will come back after treatment, when the extent of the skin cancer is not known, or when the goal is to save as much healthy skin as possible, such as with cancers near the eye or other critical areas such as the central face, ears or fingers”. The process of Mohs surgery is fairly simple. The surgeon removes a small layer of skin containing the cancerous cells and examines it under the microscope. They will continue removing layers of skin until no abnormal cells are viewed. This type of surgery is common because only the cancerous skin is removed while the healthy skin remains intact. Patients will have a scar after this procedure, but it will most likely be smaller compared to scars from other surgery methods. Mohs surgery “has the highest overall cure rate — about 94-99 percent — of any treatment for BCC”. The only downside to this procedure is that it is very time consuming and the individual may have to visit the doctor multiple times in order to remove all the cancerous cells.

Another, more damaging, form of surgery is curettage and electrodesiccation (ED&C). “Curettage and electrodesiccation is a good treatment for superficial (confined to the top layer of skin) basal cell and squamous cell cancers”(10). It is also common for people to go through this procedure if the cancer is present on their legs or ears (11). This is due to the fact that more skin can be removed from these parts of the bodies.

During ED&C, the surface of the skin cancer is removed with a scraping tool called a curette (11). The area is then seared with an electric needle called an electrode that destroys any remaining cancer cells. This process is more time efficient compared to Mohs, as an individual can have the process repeated once or twice during the same visit and then be done. However, this procedure leaves a crusty scab that takes many weeks to heal and eventually leaves a large scar. There is also a higher probability for the cancer to return when ED&C is used.

In order to avoid surgery and the resulting scars, there has been more research conducted in topical creams to treat basal cell carcinoma. Fluorouracil cream has recently been used when treating skin cancers. “Fluorouracil belongs to the category of chemotherapy called antimetabolites. Antimetabolites are very similar to normal substances within the cell. When the cells incorporate these substances into the cellular metabolism, they are unable to divide”. When the cancer cells stop dividing, they will be unable to spread to other parts of the body and will eventually die. With Fluorouracil, the individual applies the cream to the target area multiple times a day. In general, cancer patients “should continue using it until the lesions are gone. This usually takes at least 3 to 6 weeks, but may take as long as 10 to 12 weeks”.

There are definitely more risks for using this product. Harmful chemicals are being applied to the skin and there is not a lot of control over how and if the cancer will be removed. It is especially not recommended to put on the face – a common place for individuals with basal cell carcinoma. In more than 30% of cases, individuals have experienced side effects including pain, itching, burning, dryness, and swelling in the area where this cream has been applied (13). These side effects have been noted to go away after use of this cream has stopped. It is also reported that there is a greater chance of the cancer reappearing for those who use a cream instead of getting the tumor surgically removed. Overall, I believe surgery is the best method for removing basal cell carcinoma.

Despite the cancer being removed, people who have had this form of cancer have to continue visiting the doctors for the rest of their lives. It is recommended that they come for a skin check up every six months, where their body will be examined for any legions that may appear. For basal cell carcinoma, reoccurrences often happen within the first two years after the surgery. Patients are also recommended to wear sunscreen and avoid tanning after being diagnosed with BCC. Any additional sun damage will significantly increase the chance of the person getting cancer again.

After surgery and removing multiple layers of skin to get rid of all cancerous cells, John won his battle with cancer. He now makes sure to always wear sunscreen and a hat when outside in order to prevent exposure to UV rays and lower that chances of future skin cancer. His children grumble and reluctantly put on sunscreen before playing in the sun, as John reminds them that they have a higher risk of developing skin cancer and should take any measures possible for preventing it. After five years, he remains cancer-free, but every time he looks in the mirror, he sees the scar on his upper lip and is reminded of his journey with basal cell carcinoma.

Aperçu: While the treatment for basal cell carcinoma is very effective and the survival rate is almost 100%, the consequences of too much sun exposure will follow you for the rest of your life. The scar you have will be a constant reminder of your journey with this cancer.