Genetics of basal cell carcinoma induction, maintenance

Philadelphia - Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are just two examples of non-melanoma skin cancer.

They are much more common than malignant melanoma, having an incidence in the United States of more than one million cases a year, and their incidence is on the rise.

Because they are locally invasive, but rarely metastatic malignant tumors, they can be quite disfiguring and require immediate medical attention, and they must be dealt with head-on by a dermatologist.

Understanding the pathogenesis of these epithelial cancers may be the key in finding novel anti-tumor therapeutics, according to Anthony E. Oro, M.D., Ph.D., assistant professor in the department of dermatology at Stanford University's Comprehensive Cancer Center, Palo Alto, Calif.

He shared his long years of experience and insight on how to best treat these epithelial tumors at the 2006 annual meeting of the Society for Investigative Dermatology, here.

It is an undisputed fact that the main risk factor for nonmelanoma skin cancer is directly related to ultraviolet exposure. Age, location on the body and photocarcinogens all play a role in the prevalence of SCC and BCC. According to Dr. Oro, melanoma, SCC and BCC have different etiologies and different precursors. Mutations in genes like CDK4 and Ras seem to be the etiologies for SCC with actinic keratoses and SCC in situ its precursors. The sonic hedgehog signaling system plays a central role in the etiology of BCC. Malignant melanoma has different etiologies, such as Ras/Raf3, Ink4A and TERT and different precursors, namely dysplastic nevi and melanoma in situ.

Dr. Oro tells Dermatology Times that in basal cell nevus syndrome, 50 percent or more of these patients have BCCs, rib abnormalities, spina bifida occulta, ovarian cysts, odontogenic jaw keratocysts, palmar and/or plantar pits, epidermal cysts and, less commonly, medulloblastomas, polydactyly, meningiomas, as well as enlarged body size.

The sonic hedgehog signaling system plays a part in up to 25 percent of human cancers and underlies many birth defects. Interestingly, many of these are seen in a patient with the basal cell nevus syndrome, including BCCs, rib and jaw defects, polydactyly as well as medulloblastomas.

Dr. Oro mentions that there are five other inherited BCC tumor susceptibility syndromes, namely multiple hereditary infundibulocystic basal cell carcinoma (MHIBCC) demonstrating a histologic variant of BCC; generalized basaloid follicular hamartoma syndrome (GBFHS) with BCC-like lesions; multiple trichofolliculoma syndrome; and Bazek-Dupre-Christol syndrome and Rombo syndrome, which demonstrate BCCs in patients. Understanding the genetic basis of these and other syndromes may be very helpful to further understanding skin cancer.

Treatment of choice

Surgery (Mohs or excision) is the current treatment of choice for BCC, Mohs surgery boasting an 88 percent to 95 percent cure rate.

Radiation therapy is used in nonsurgical candidates and proves effective, but could lead to a second BCC. Other treatments include 5-fluorouracil cream, gamma interferon, retinoids, chemoprevention with green tea, as well as imiquimod 5 percent cream - acting as an immunomodulator and proving to be very successful against superficial BCCs.