RUNX3 protein is overexpressed in human basal cell carcinomas

Basal cell carcinomas (BCC), which are the most common form of skin malignancy, are invariably associated with the deregulation of the Sonic Hedgehog (Shh) signalling pathway. As such, BCC represent a unique model for the study of interactions of the Shh pathway with other genes and pathways. We constructed a tissue microarray (TMA) of 75 paired BCC and normal skin and analysed the expression of beta-catenin and RUNX3, nuclear effectors of the wingless-Int (Wnt) and bone morphogenetic protein/transforming growth factor-beta pathways, respectively. In line with previous reports, we observed varying subcellular expression pattern of beta-catenin in BCC, with 31 cases (41%) showing nuclear accumulation. In contrast, all the BCC cases tested by the TMA showed RUNX3 protein uniformly overexpressed in the nuclei of the cancer cells. Analysis by Western blotting and DNA sequencing indicates that the overexpressed protein is normal and full-length, containing no mutation in the coding region, implicating RUNX3 as an oncogene in certain human cancers. Our results indicate that although the deregulation of Wnt signalling could contribute to the pathogenesis of a subset of BCC, RUNX3 appears to be a universal downstream mediator of a constitutively active Shh pathway in BCC.

Role of dietary factors in the development of basal cell cancer and squamous cell cancer of the skin

The role of dietary factors in the development of skin cancer has been investigated for many years; however, the results of epidemiologic studies have not been systematically reviewed. This article reviews human studies of basal cell cancer (BCC) and squamous cell cancer (SCC) and includes all studies identified in the published scientific literature investigating dietary exposure to fats, retinol, carotenoids, vitamin E, vitamin C, and selenium. A total of 26 studies were critically reviewed according to study design and quality of the epidemiologic evidence. Overall, the evidence suggests a positive relationship between fat intake and BCC and SCC, an inconsistent association for retinol, and little relation between ß-carotene and BCC or SCC development. There is insufficient evidence on which to make a judgment about an association of other carotenoids with skin cancer. The evidence for associations between vitamin E, vitamin C, and selenium and both BCC and SCC is weak. Many of the existing studies contain limitations, however, and further well-designed and implemented studies are required to clarify the role of diet in skin cancer. Additionally, the role of other dietary factors, such as flavonoids and other polyphenols, which have been implicated in skin cancer development in animal models, needs to be investigated.

Antioxidants and basal cell carcinoma of the skin : a nested case-control study

Objective To investigate the relationship between basal cell carcinoma (BCC) and antioxidant nutrients, specifically carotenoids, vitamin E and selenium.

Methods The Nambour Skin Cancer Study is an ongoing, community-based study of randomly selected adult residents of a township in sub-tropical Queensland, Australia. Using a nested case–control design, incident cases of BCC (n=90) were compared with age and sex matched controls (n=90). Dietary exposure was measured using food frequency questionnaire estimates of intake as well as serum biomarkers. Other determinants of skin cancer including sun exposure were also considered. Dietary intakes were adjusted for energy intake, and serum carotenoids and vitamin E were adjusted for serum cholesterol. Odds ratios were calculated across quartiles of dietary intake and serum biomarkers and linear trends were assessed using logistic regression, adjusting for age, sex and supplement use.

Results and conclusions In this prospective study no significant associations were found between BCC and carotenoids, vitamin E or selenium, as measured by serum biomarkers or dietary intake, although there was a suggestion of a positive association with lutein intake.

Corrective eyeglasses and medial canthal basal cell carcinoma: a case-control study

Background Corrective eyeglasses are frequently worn by adults, particularly at older ages. Their lenses and frames provide ultraviolet protection. Medial canthal basal cell carcinomas are infrequent (38%), and their relation with the use of corrective glasses was not yet investigated. Objectives To assess the prevalence of corrective eyeglasses use in individuals with medial canthal basal cell carcinoma. Methods Case-control study using two controls matched by age, gender, and ethnicity for each case. Cases were patients with medial canthal basal cell carcinoma, and controls were patients with basal cell carcinoma elsewhere on the face. The prevalence of major risk variables was estimated and adjusted by conditional multiple logistic regression. Results Fifty cases and 100 controls were assessed. The mean patient age was 69.7 years, and 54% of the subjects were females. No difference regarding the eyeglasses use or use duration was found between groups. However, when visual defects were separately evaluated, eyeglasses for myopia correction were independently associated with lower risk of medial canthal basal cell carcinoma development (OR = 0.26; P = 0.03), what can be related to long term local photoprotection. Conclusion The use of eyeglasses for myopia correction is associated with lower prevalence of medial cantal basal cell carcinoma. Risk-reducing mechanisms should be elucidated.

Multiple cytogenetic clones in a basal cell carcinoma

Chromosome analysis of short-term culture of a basal cell carcinoma showed five clonal chromosome abnormalities, t(9;14)(q12 or q13;p11), del(1)(q23 or q25), trisomy 5, trisomy 7, and monosomy X. In addition, several nonclonal structural and numerical changes were seen in the tumor cells.

Translocation (4;14) and concomitant inv(14) in a basal cell carcinoma

Chromosome analysis of short-term cultures from a basal cell carcinoma was performed. The analyzed karyotypes showed a pseudodiploid clone characterized by a der(4)t(4;14)(p14;p11) and a concomitant inversion of the same chromosome 4 involved in the t(4;14) with the breakpoints at p14 and q25.

Cytogenetic findings in two basal cell carcinomas

We describe the cytogenetic study of two basal cell carcinomas. Only single chromosomally abnormal clones could be detected in both. In addition, many nonclonal changes were seen in the samples, which may represent small neoplastic clones or the result of a basic molecular defect induced by carcinogens.

Immunohistochemical aspects of basal cell adenoma and canalicular adenoma of salivary glands

Basal cell adenoma is a benign epithelial neoplasm with a uniform histologic appearance dominated by basaloid cells. Those cells may be distributed in various arrangements as solid, trabecular, tubular and membranous. Canalicular adenoma is also a benign neoplasm composed by columnar cells arranged in branching and interconnecting cords of single or double cell thick rows. There is some disagreement among investigators about whether canalicular adenoma should be included within the basal cell adenoma histologic spectrum. In the present study we compared the expression of cytokeratins (CK), vimentin and muscle-specific actin, utilizing immunohistochemical technique, in three cases diagnosed as basal cell adenomas predominantly of the solid type, and three cases of canalicular adenomas. The results obtained showed a distinct immunoprofile for both neoplasms. Solid areas of basal cell adenomas did not stain for any of the tested antibodies; only when there was tubular differentiation, those structures expressed CKs 7, 8, 14, and 19 in luminal cells and vimentin in non-luminal cells. On the other hand, canalicular adenomas strongly expressed CKs 7 and 13. The panel of antibodies utilized supports the separation of the two entities. © 2001 Elsevier Science Ltd.