Pigmentation, Melanocyte Colonization, and p53 Status in Basal Cell Carcinoma

Lídia M Frey, Roland Houben, Eva-B Bröcker, Lídia M Frey, Roland Houben, Eva-B Bröcker

Abstract

Basal cell carcinoma (BCC) is the most common neoplasm in the Caucasian population. Only a fraction of BCC exhibits pigmentation. Lack of melanocyte colonization has been suggested to be due to p53-inactivating mutations in the BCC cells interfering with the p53-proopiomelanocortin pathway and the production of alpha melanocyte-stimulating hormone in the tumor. To evaluate this, we determined tumor pigmentation as well as expression of melan-A and of p53 in 49 BCC tissues by means of immunohistochemistry. As expected, we observed a positive relation between tumor pigmentation and melan-A positive intra-tumoral melanocytes. Melanocyte colonization and, to a lesser extent, p53 overexpression showed intraindividual heterogeneity in larger tumors. p53 overexpression, which is indicative of p53 mutations, was not correlated to melanocyte colonization of BCC. Sequencing of exon 5-8 of the p53 gene in selected BCC cases revealed that colonization by melanocytes and BCC pigmentation is neither ablated by p53 mutations nor generally present in BCCs with wild-type p53.

Figures

Figure 1
Figure 1
Correlation of pigmentation with melanocyte colonization (a) and lack of correlation between p53 positivity and melanocyte colonization. (b) 49 BCC tissue sections were analyzed immunohistochemically for the presence of melanin, the expression of the melanocyte marker melan-A and p53 expression. The frequency of melanin- and p53-positive tumor cells as well as the frequency of melan-A-expressing melanocytes was scored. (a) The correlation between melanocytes and pigmentation was statistically significant (P < .0001). (b) There was no correlation between the frequency of melanocytes and p53 expression (P = .77).
Figure 2
Figure 2
Melanocytic colonization in a BCC expressing mutant p53. Depicted are immunohistochemically stained tissue sections of a BCC displaying approximately 10% melan-A positive melanocytes (a) and high levels of nuclear p53 in 90% of the tumor cells (c). The specimen shows strong pigmentation in the centre of the lesion (b), and sequencing revealed the presence of a c380t mutation leading to an S127F amino acid exchange (d).

References

    1. Roewert-Huber J, Lange-Asschenfeldt B, Stockfleth E, Kerl H. Epidemiology and aetiology of basal cell carcinoma. British Journal of Dermatology. 2007;157(2):47–51.
    1. Schiessl C, Wolber C, Tauber M, Offner F, Strohal R. Treatment of all basal cell carcinoma variants including large and high-risk lesions with 5% imiquimod cream: histological and clinical changes, outcome, and follow-up. Journal of Drugs in Dermatology. 2007;6(5):507–513.
    1. Epstein EH. Basal cell carcinomas: attack of the hedgehog. Nature Reviews Cancer. 2008;8(10):743–754.
    1. Cui R, Widlund HR, Feige E, et al. Central role of p53 in the suntan response and pathologic hyperpigmentation. Cell. 2007;128(5):853–864.
    1. Florell SR, Zone JJ, Gerwels JW. Basal cell carcinomas are populated by melanocytes and Langerhan’s cells. American Journal of Dermatopathology. 2001;23(1):24–28.
    1. Roulet F. Methoden der pathologischen Histologie. Wien, Germany: Springer; 1948.
    1. Busam KJ, Jungbluth AA. Melan-A, a new melanocytic differentiation marker. Advances in Anatomic Pathology. 1999;6(1):12–18.
    1. Hashimoto K, Fujiwara K, Mehregan A. Current topics of immunohistochemistry as applied to skin tumors. Journal of Dermatology. 1993;20(9):521–532.
    1. Blagosklonny MV. Loss of function and p53 protein stabilization. Oncogene. 1997;15(16):1889–1893.
    1. Midgley CA, Lane DP. P53 protein stability in tumour cells is not determined by mutation but is dependent on Mdm2 binding. Oncogene. 1997;15(10):1179–1189.
    1. Cesarman E, Inghirami G, Chadburn A, Knowles DM. High levels of p53 protein expression do not correlate with p53 gene mutations in anaplastic large cell lymphoma. American Journal of Pathology. 1993;143(3):845–856.
    1. Salopek TG. Induction of melanogenesis during the various melanoma growth phases and the role of tyrosinase, lysosome-associated membrane proteins, and p90 calnexin in the melanogenesis cascade. Journal of Investigative Dermatology Symposium Proceedings. 1996;1(2):195–202.
    1. Betti R, Gualandri L, Cerri A, Inselvini E, Crosti C. Clinical features and histologic pattern analysis of pigmented basal cell carcinomas in an Italian population. Journal of Dermatology. 1998;25(10):691–694.
    1. Bourdon JC. p53 and its isoforms in cancer. British journal of cancer. 2007;97:277–282.
    1. Levine AJ, Hu W, Feng Z. The P53 pathway: what questions remain to be explored? Cell Death and Differentiation. 2006;13(6):1027–1036.
    1. Slominski A, Tobin DJ, Paus R. Does p53 regulate skin pigmentation by controlling proopiomelanocortin gene transcription? Pigment Cell Research. 2007;20(4):307–308.
    1. Sanchez-Más J, Hahmann C, Gerritsen I, Garcia-Borrón JC, Jiménez-Cervantes C. Agonist-independent, high constitutive activity of the human melanocortin 1 receptor. Pigment Cell Research. 2004;17(4):386–395.
    1. Slominski A, Plonka PM, Pisarchik A, et al. Preservation of eumelanin hair pigmentation in proopiomelanocortin-deficient mice on a nonagouti (a/a) genetic background. Endocrinology. 2005;146(3):1245–1253.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe