Comparison of EMA,CEA, CD10 and Bcl-2 Biomarkers by Immunohistochemistry in Squamous Cell Carcinoma and Basal Cell Carcinoma of the Skin

  • Ramezani, Mazaher ;
  • Mohamadzaheri, Elham ;
  • Khazaei, Sedigheh ;
  • Najafi, Farid ;
  • Vaisi-Raygani, Asad ;
  • Rahbar, Mahtab ;
  • Sadeghi, Masoud
  • Published : 2016.04.11


Background: Basal and squamous cell carcinoma (BCC and SCC) are the most common skin cancers worldwide and distinction between the two may sometimes be very difficult in routine histopathology. The present study was aimed to evaluate a reliable diagnostic method for these cancers based on immunohistochemistry (IHC). Materials and Methods: IHC was used with antibodies to Bcl-2, CD10, CEA, and EMA biomarkers, which despite non-specificity are easily available for detection of various types of tumors in pathology sections and can be used as a panel for differentiation. In this descriptive and analytic study, paraffin-embedded blocks of 29 SCC patients and 29 BCC patients were collected and sectioned for IHC staining. The results were analyzed by the STATA (version 8) statistical package using the Chi-square test. Results: BCC patients were 100%, 75.8%, 0% and 0% positive for Bcl-2, CD10, CEA and EMA markers, respectively, and for SCC patients were 3.5%, 0%, 34.5% and 82.7% positive, respectively. Using simultaneously Bcl-2 and CD10 as positive markers, detection of BCC with 88% accuracy and 100% specificity was possible, while application of CEA and EMA positivity could detect SCC with 67% accuracy and 100% specificity. Conclusions: SCC and BCC have different immunostaining profiles; therefore, Bcl-2, CD10, CEA and EMA markers can be helpful to distinguish between them.


Skin cancer;BCC;SCC;differential diagnosis;immunohistochemistry;markers


  1. Aiad HA, Hanout HM (2007). Immunohistochemical expression of CD10 in basal and squamous cell carcinomas. J Egypt Natl Cancer Inst, 19, 195-201.
  2. Alhumaidi A (2012). Practical immunohistochemistry of epithelial skin tumor. Indian J Dermatol Venereol Leprol, 7, 698-708.
  3. Ansai S, Takeichi H, Arase S, et al (2011). Sebaceous carcinoma: an Immunohistochemical reappraisal. Am J Dermatopatho, 33, 579-87.
  4. Beer TW, Shepherd P, Theaker JM (2000). Ber EP4 and epithelial membrane antigen aid distiniction of basal cell, squamous cell and basosquamous carcinoma of the skin. Histopathol, 37, 218-23.
  5. Firnhaber JM (2012). Diagnosis and treatment of basal cell and squamous cell carcinoma. Am Fam Physician, 86, 161-8.
  6. Halpern AC, Hanson LJ (2004). Awareness of, knowledge of and attitudes to nonmelanoma skin cancer (NMSC) and actinic keratosis (AK) among physicians. Int J Dermatol, 43, 638-42.
  7. Heyderman E, Graham RM, Chapman DV, et al (1984). Epithelial markers in primary skin cancer: an immunoperoxidase study of the distribution of epithelial membrane antigen(EMA) and carcinoembryonic antigen (CEA) in 65 primary skin carcinomas. Histopathol, 8, 423-34.
  8. Juan Rosai (2004). Skin. In: Juan Rosai, editor. Rosai and Ackermans surgical pathology, 9th edition, mosby, 133-138.
  9. Leiter U, Garbe C (2008). Epidemiology of melanoma and nonmelanoma skin cancer--the role of sunlight. Adv Exp Med Biol, 624, 89-103.
  10. Lo Muzio L, Mignogna MD, Pannone G, et al (2003). Expression of bcl-2 in oral squamous cell carcinoma: an immunohistochemical study of 90 cases with clinico-pathological correlations. Oncol Rep, 10, 285-91.
  11. Morales-Ducret CR ,Van de Rijn M, LeBrun DP, et al(1995). Bcl-2 expression in primary malignancies of the skin. Arch Dermatol, 131, 909-12.
  12. Nakagawa K, Yamamura K, Maeda S, et al (1994). Bcl-2 expression in epidermal keratinocyticdiseases. Cancer, 74, 1720-4.<1720::AID-CNCR2820740613>3.0.CO;2-T
  13. Niu Y, Zhou Z, Liu F, et al (2002). Expression of P16 and Bcl-2 protein in malignant eyelid tumors. Chin Med J (Engl), 115, 21-5.
  14. Puizina-Ivic N, Sapunar D, Marasovic D, et al (2008). An overview of Bcl-2 expression in histopathological variants of basal cell carcinoma, squamous cell carcinoma, actinic keratosis and seborrheickeratosis. Coll Antropol, 32, 61-65.
  15. Radic J, Batinac T, Hadzisejdic I, et al (2011). Concurrent basal cell and squamous cell carcinomas associated with hydroxyureatherapy. Acta Dermatovenerol Croat, 19, 183-6.
  16. Rajabi P, Aboutalebdokht M, Heidarpour M, et al (2007). Evaluation of diagnostic values of EMA and Ber-Ep4 in distinction between basal cell carcinoma and squamous cell carcinoma of the skin. Iranian J Pathol, 2, 7-10.
  17. Scurry J, de Boer WG (1983). carcinoembryonic antigen in skin and related tumors as determined by immunohistological techniques. Pathol, 15, 379-84.
  18. Sinard JH (1999). Immunohistochemical distinction of ocular sebaceous carcinoma from basal cell and squamous cell carcinoma. Archophthalmol, 117, 776-83.
  19. Sramek B, Lisle A, Loy T (2008). Immunohistochemistry in ocular carcinomas. J Cutan Pathol, 35, 641-6.
  20. Tebcherani AJ, de Andrade HF Jr, Sotto MN (2012). Diagnostic utility of immunohistochemistry in distinguishing trichoepithelioma and basal cell carcinoma: evalution using tissue microarray samples. Modpathol, 25, 1345-53.
  21. Verhaegh ME, Sanders CJ, Arends JW, et al (1995). Expression of the apoptosis-suppressing protein Bcl-2 in non-melanoma skin cancer. Br J Dermatol, 132, 740-4.
  22. Wagoner J, Keehn C, Morgan M (2007). CD10 Immunostaining differentiates superficial basal cell carcinoma from cutaneous squamous cell carcinoma. Am J Dermatopathol, 29, 555-58.
  23. Yada K, Kashima K, Daa T, et al (2004). Expression of CD10 in basal cell carcinoma. Am J Dermathopathol, 26, 463-71.
  24. Zheng Z , Kye Y, Zhang X, et al (2005). Expression of p63, Bcl2 and P16 in basal cell carcinoma and squamous cell carcinoma of the skin. Korean J of Pathol, 39, 91-8.

Cited by

  1. Cutaneous basal cell carcinoma with distant metastasis to thorax and bone vol.470, pp.6, 2017,
  2. Carcinoembryonic Antigen Serum Levels in Nonmelanoma Skin Cancer vol.6, pp.1, 2018,


Supported by : Research Council of Kermanshah University of Medical Sciences