EXPRESSION OF ANTI-APOPTOTIC PROTEIN BCL-2 IN CUTANEOUS BASAL CELL CARCINOMA

  • Vladimír Bartoš Department of Pathology, Faculty Hospital in Žilina, Slovakia
  • Millada Kullová Department of Dermatovenerology, Faculty Hospital in Žilina, Slovakia

Abstract

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

References

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.

Published
2018-12-31
How to Cite
1.
Bartoš V, Kullová M. EXPRESSION OF ANTI-APOPTOTIC PROTEIN BCL-2 IN CUTANEOUS BASAL CELL CARCINOMA. J Cancer Allied Spec [Internet]. 2018Dec.31 [cited 2021Sep.19];4(4). Available from: https://journals.sfu.ca/jcas/index.php/jcas/article/view/202
Section
Original Research Article