EXPRESSION OF ANTI-APOPTOTIC PROTEIN BCL-2 IN CUTANEOUS BASAL CELL CARCINOMA
Purpose: Overexpression of antiapoptotic B-cell lymphoma-2 (Bcl-2) protein is one of the major contributors to oncogenesis and high levels have been identified in a variety of tumour types. We investigated an immunohistochemical
expression of Bcl-2 protein in cutaneous basal cell carcinomas (BCCs) to elucidate whether there are differences in the expression pattern related to tumour growth phenotype.
Materials and Methods: The study group consisted of 45 cutaneous BCCs, which were categorised into the nonaggressive (NA-BCCs; 31 cases) and aggressive histologic variants (A-BCCs; 14 cases).
Results: There were 3 tumours (6.6%) with negative staining and 42 tumours (93.4%) with positive staining for Bcl-2 protein, 10 of which (23.8%) displayed low and remaining 32 cases (76.2%) exhibited high expression. All three “Bcl-
2 negative” BCCs showed aggressive-growth features (infiltrative subtypes). When Bcl-2 values were evaluated as negative/low versus high expression, there was significantly lower Bcl-2 protein expression in the A-BCCs compared
to the NA-BCCs. Even an intensity of immunostaining showed a tendency of being weaker in the A-BCCs. In spite of that, three infiltrative BCCs showed a diffuse strong immunoreactivity.
Conclusion: An immunohistochemical positivity of Bcl-2 protein in the neoplastic cells of cutaneous BCC was nearly constant feature, and its decreased staining was associated with an infiltrative growth pattern. It suggests that a low
Bcl-2 protein expression in tumor tissue might be considered an unfavorable prognostic indicator.
Key words: Basal cell carcinoma, B-cell lymphoma-2 protein, biological behavior
Dai H, Meng XW, Kaufmann SH. Bcl2 family, mitochondrial
apoptosis, and beyond. Cancer Transl Med 2016;2:7-20
Czabotar PE, Lessene G, Strasser A, et al. Control of apoptosis by the BCL-2 protein family: Implications for physiology and therapy. Nat Rev Mol Cell Biol 2014;15:49-63.
Senghal VN, Chatterjee K, Pandhi D, et al. Basal cell carcinoma: Pathophysiology. Skinmed 2014;12:176-81.
Tilli CM, Van Steensel MA, Krekels GA, et al. Molecular aetiology and pathogenesis of basal cell carcinoma. Br J Dermatol 2005;152:1108-24.
Verhaegh ME, Sanders CJ, Arends JW, et al. Expression of the apoptosis-suppressing protein Bcl-2 in non-melanoma skin cancer. Br J Dermatol 1995;132:740-4.
Crowson AN, Magro CM, Kadin ME, et al. Differential expression of the bcl-2 oncogene in human basal cell carcinoma. Hum Pathol 1996;27:355-9.
Delehedde M, Cho SH, Sarkiss M, et al. Altered expression of bcl-2 family member proteins in nonmelanoma skin cancer. Cancer 1999;85:1514-22.
Ramdial PK, Madaree A, Reddy R, et al. Bcl-2 protein expression in aggressive and non-aggressive basal cell carcinomas. J Cutan Pathol 2000;27:283-91.
Cho S, Hahm JH, Hong YS. Analysis of p53 and BAX mutations, loss of heterozygosity, p53 and BCL2 expression and apoptosis in basal cell carcinoma in Korean patients. Br J Dermatol 2001;144:841-8.
Bozdogan Ö, Erkek E, Atasoy P, et al. Bcl-2-related proteins, a-smooth muscle actin and amyloid deposits in aggressive and non-aggressive basal cell carcinomas. Acta Derm Venereol 2002;82:423-7.
Zheng Z, Kye Y, Zhang X, et al. Expression of p63,bcl-2,bcl-6 and p16 in basal cell carcinoma and squamous cell carcinoma of the skin. Korean J Pathol 2005;39:91-8.
Puizina-Ivić N, Sapunar D, Marasović D, et al. An overview of bcl-2 expression in histopathological variants of basal cell carcinoma, squamous cell carcinoma, actinic keratosis and seborrheic keratosis. Coll Antropol 2008;32 Suppl 2:61-5.
Corrêa Mde P, Ferreira AP, Gollner AM, et al. Markers expression of cell proliferation and apoptosis in basal cell carcinoma. An Bras Dermatol 2009;84:606-14.
Tebcherani AJ, de Andrade HF Jr., Sotto MN. Diagnostic utility of immunohistochemistry in distinguishing trichoepithelioma and basal cell carcinoma: Evaluation using tissue microarray samples. Mod Pathol 2012;25:1345-53.
Sivrikoz ON, Kandiloğlu G. The effects of cyclin D1 and Bcl-2 expression on aggressive behavior in basal cell and basosquamous carcinoma. Iran J Pathol 2015;10:185-91.
Ramezani M, Mohamadzaheri E, Khazaei S, et al. Comparison of EMA,CEA, CD10 and bcl-2 biomarkers by immunohistochemistry in squamous cell carcinoma and basal cell carcinoma of the skin. Asian Pac J Cancer Prev 2016;17:1379-83.
Vidal D, Matías-Guiu X, Alomar A. Efficacy of imiquimod for the expression of bcl-2, ki67, p53 and basal cell carcinoma apoptosis. Br J Dermatol 2004;151:656-62.
Urosevic M, Maier T, Benninghoff B, et al. Mechanisms underlying imiquimod-induced regression of basal cell carcinoma in vivo. Arch Dermatol 2003;139:1325-32.
Otsuka A, Dreier J, Cheng PF, et al. Hedgehog pathway inhibitors promote adaptive immune responses in basal cell carcinoma. Clin Cancer Res 2015;21:1289-97.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Authors retain copyright and grant the Journal of Cancer & Allied Specialties (JCAS) right-of-first publication. In addition, the work will be simultaneously licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International license. This license allows others to share the work in whole or part (for non-commercial purpose), with an acknowledgement of the work’s authorship and initial publication in JCAS.
Furthermore, authors are free to enter into separate contractual arrangements for the non-exclusive distribution of the journal’s published version of the work, with an acknowledgement of its initial publication in this journal.
Authors are permitted and encouraged to share their work online or in medical or scientific conferences prior to or during submission process.