Proposal of a Provisional Classification of Sebaceous Carcinoma Based on Hormone Receptor Expression and HER2 Status

Abstract

Despite recent progress in comprehensive genetic analysis, little is known about the molecular pathogenesis of sebaceous carcinoma. On the basis of the ontogenic proximity of sebaceous and mammary glands, we designed an intrinsic classification for sebaceous carcinoma adapted from that of breast cancer and evaluated its clinical significance. We investigated 42 cases of sebaceous carcinoma, including 32 ocular and 10 extraocular cases. Immunohistochemical analyses for estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), HER2, Ki67, and CK5/6 and fluorescence in situ hybridization for the HER2 gene were performed. The immunohistochemistry for ER, PR, and AR showed positivity in 18 (42.9%), 11 (26.2%), and 34 (81.0%) cases, respectively. Expression of the HER2 protein was found in 10 (33.8%) cases, whereas extra copies were found in 3 (7.1%). According to our system, there were 16 (38.1%) cases of the luminal 1 subtype, 4 (9.5%) of the luminal 2 subtype, and 7 (16.7%) of the HER2 subtype, respectively. Fifteen cases (35.7%) belonged to the triple-negative group. In univariable analysis, loss of AR was significantly associated with shorter disease-free survival (P = 0.020), whereas the expression of HER2 was associated with a better outcome with borderline significance (P = 0.060). The luminal 2 subtype showed the best survival, and the all-negative subtype showed the worst (P = 0.001). In multivariable analysis, negativity of PR or AR, low CK5/6, and female sex were independent poor prognostic factors (all P < 0.05). This is the first study to categorize sebaceous carcinoma on the basis of the possible link between its molecular pathogenesis and future therapeutic applications.