Immunohistochemical Expression of CK19, AR, PHLDA1, CD10 and Ki67 in the Differentiation between Trichoepithelioma and Basal Cell Carcinoma: A Systematic Review

Abstract

Background. Basal cell carcinoma (BCC) and trichoepithelioma (TE) are follicular adnexal neoplasms that arise from the follicular germ but with divergent biological behavior. The gold standard in the differentiation is through histopathological examination using hematoxylin and eosin (H and E) stain. There are cases, however, when the distinction is not straightforward.

Objective. To assess the association and diagnostic accuracy of the immunohistochemical (IHC) expressions of CD10, Ki67, CK19, androgen receptor (AR), and PHLDA1 in distinguishing between basal cell carcinoma and trichoepithelioma.

Methods. We conducted a comprehensive search on cross-sectional studies on human tissue from 2000 to 2020 in MEDLINE (PubMed), CENTRAL and EMBASE for comparative studies and reference lists. The data were summarized and analyzed using Microsoft Excel and RevMan. We used Chi-square test for independence, summary receiver operator curves (sROC), and diagnostic odds ratio (OR).

Results. We included 15 articles containing 686 BCC and 367 TE in the systematic review. The pooled staining of biomarkers showed a significant difference in the staining of CK19 (p<0.05) and AR (p<0.0001), and PHLDA1 (p<0.0001). Diagnostic odds ratio was used to confirm these associations. AR was found to have the highest odds in the diagnosis of BCC (OR 27.92, 95% CI 10.69, 72.86). The pattern of staining of CD10 is significant (p<0.001) with staining of both tumor and stroma (OR 8.09, 95% CI 4.57, 13.53) and staining of tumor alone (OR 8.15, 95% CI 4.56, 14.35) (p<0.001) in the diagnosis of BCC. CD10 stromal staining, on the other hand, is significantly associated with the diagnosis of TE (OR 7.26, 95% CI 5.06, 10.44) (p<0.0001). There is no significant association between Ki67 staining (OR 1.22, 95% CI 0.48, 3.09) (p=0.67) and the diagnosis of BCC. The forest plot and sROC showed that AR had high specificity across all included studies in the diagnosis of basal cell carcinoma, while PHLDA1 demonstrated high specificity and high sensitivity in diagnosing trichoepithelioma.

Conclusion. The biomarkers AR and PHLDA1 are useful as an initial panel to distinguish between BCC and TE, given that both showed high sensitivity as well as significant association with BCC and TE respectively. CD10 and CK19 may also be used with AR and PHLDA1 for further confirmation.