Assessment of Syndecan-1 (CD138) and Ki-67 Expression for Differentiating Keratoacanthoma and Squamous Cell Carcinoma

March 2013 | Volume 12 | Issue 3 | Original Article | 53 | Copyright © March 2013

Lorena Lammoglia-Ordiales MD,a Judith Dominguez-Cherit MD,a Samantha Rivera-Macías DDM,b Alma A. Rodriguez-Carreón MD,a Verónica Fonte-Avalos MD,a Martha Contreras-Barrera MD,a and Sonia Toussaint-Caire MDa

aHospital General Dr. Manuel Gea González, Dermatology Department, Mexico City, Mexico bUniversidad Autónoma Metropolitana, Oral Pathology Department, Mexico City, Mexico

BACKGROUND: There is a major controversy over the natural behavior of keratoacanthoma (KA). KAs have been described as benign lesions, but also as variants of squamous cell carcinoma (SCC). Microscopic differentiation between these 2 entities is problematic, and sometimes impossible. Syndecan-1 (CD138) is an adhesion molecule whose expression appears to be inversely correlated with tumor invasiveness. Elevated Ki-67 expression is indicative of a high proliferation index, a feature of malignant tumors.
METHODS: Syndecan-1 and Ki-67 expression were assessed in 22 KA skin samples and in 17 SCC skin biopsies.
RESULTS: Syndecan-1 expression was diminished in the SCC specimens compared with the KA specimens (P=.000). Ki-67 expression was increased in the SCC specimens compared with the KA specimens, with mean values of 9 and 0.08, respectively (P=.000).
LIMITATIONS: Further studies that compare intermediate risk KAs to typical KAs and SCCs are required to corroborate these findings.
CONCLUSION: The assessment of syndecan-1 and Ki-67 expression in skin biopsies is a helpful tool for differentiating KA and SCC.

J Drugs Dermatol. 2013;12(3):e53-e58.


Keratoacanthomas (KAs) are tumors of epidermal origin characterized by a rapid growth rate. Since 1950, there has been controversy as to whether KAs are pseudobenign tumors with a distinct clinical behavior or pseudomalignant tumors and the potential of progressing to squamous cell carcinomas (SCCs), as well as to how they should be treated.1-13 Squamous cell carcinoma is the second most frequent form of skin cancer, representing 20% after basal cell carcinomas.1,3,8,9,12,13
The actual incidence of KA is unknown because many lesions are treated as SCCs and others are not treated by physicians at all because of their tendency to regress spontaneously. In various studies, the reported incidence ranges from 22.1 to 150 cases in populations of 100,000 inhabitants.4,8,11
Differentiating between KA and SCC is crucial because the therapeutic approach for each pathological entity is substantially different. In the case of KA, treatment consists of extirpating the lesion, whereas SCC treatment requires the excision of the lesion, with margins up to 1 cm wide to warrant a higher cure rate.1,4,8,14
Histopathologic examination remains the golden standard for diagnosis.1,2,8,10,14 Diagnosing KA is a difficult matter because its histopathologic criteria have little sensibility and specificity.1,2,8,10,15 The ambiguity in the diagnostic methods that are currently used to differentiate these 2 entities results in increased health care costs, the need for reinterventions, and increases in patient morbidity attributable to the reconstructive treatments.
The syndecan family is made up of heparan sulphate proteoglycans that are present on the cell surface. These molecules are important to the cell’s cohesion and adhesion functions, allowing it to maintain its normal architecture as well as to migrate, differentiate itself, and grow.16-18 Syndecan-1 (CD138) is important in the progression of neoplastic cells to their metastatic phenotype.19-22 In SCCs of the head, neck, and larynx, the lesser expression of syndecan-1 is related to a more aggressive tumor behavior. Various studies have reported its use as a carcinoma prognostic marker.16-18,20,22-26
Ki-67 is a protein that is probably needed for cellular proliferation. It is associated with ribosomal RNA transcription, and its inactivation therefore leads to inhibition of RNA synthesis. Thanks to this, Ki-67’s expression is helpful in determining the growth rate of a cellular population.27-29
Differences in the expression patterns of syndecan-1 and Ki-67, in both KA and SCC, have been described. A correlation between the expression of both immunomarkers has not however been established.20,22,30