PRAME Expression in Adnexal Lesions and Common Skin Cancer-Types: Biomarker with Potential Diagnostic Utility
Abstract
Introduction and Objective. PRAME (PReferentially expressed Antigen in MElanoma) is a tumor-associated antigen first identified in tumor-reactive T-cell clones derived from a patient with metastatic melanoma. IHC for PRAME is useful for diagnostic purposes to support a suspected diagnosis of melanoma. Anecdotally, PRAME has been observed to stain sebaceous units in glands in background skin. We examined the expression of PRAME in adnexal lesions and common skin cancers to determine whether it is of potential diagnostic utility in distinguishing between sebaceous and non-sebaceous neoplasms. Methods. IRB approval from Mount Sinai Medical Center (MSMC) was obtained. In total, 81 patients were included: sebaceous lesions (17 cases with normal sebaceous glands, hyperplasia, heterotopia, adenoma, steatocystoma, epithelioma, carcinoma); sweat gland lesions (32 cases with hyperplasia, syringoma, hidradenoma, hidrocystoma, poroma, spiradenoma, papillary hidradenoma, and carcinoma); follicular lesions (13 cases with trichodenoma, pilomatricoma, trichilemmal cyst); basal cell carcinoma (BCC; 10 cases); squamous cell carcinoma (SCC; 9 cases). Cases from MSMC between January 01, 2012, and December 31, 2023, were included. Staining intensity was subcategorized into negative, weak, moderate, and strong, whereas expression percentage positivity into 0%, 1-25%, 26-50%, 51-75%, 76-100%. Results. We found that most sebaceous (vs. non-sebaceous) lesions exhibited positive PRAME expression (CYTOPLASMIC staining) of moderate to strong intensity in >75% of cells. PRAME has a sensitivity and specificity of 100.0% and 86.7%, respectively, for sebaceous vs. non-sebaceous adnexal lesions. Also, BCCs and SCCs show weak to moderate NUCLEAR staining for PRAME (mostly in >75% of cells). Of the 13 lesions of hair follicle origin, none expressed PRAME. Of the 32 lesions of sweat gland origin, 26 (81.25%) did NOT express PRAME while 6 (18.75%) expressed PRAME. Our observations demonstrated that the greater the maturation of sebaceous units (higher proportion of mature sebocytes), the stronger the PRAME staining is. Therefore, primitive sebocytes tend to lose PRAME, and PRAME stain diminishes towards the center of the sebaceous unit (strong at the periphery). Conclusions-Implications. We confirm the potential utility of PRAME for distinguishing (1) sebaceous from non-sebaceous adnexal neoplasms and (2) BCC and SCC (that may show nuclear staining) from sebaceous carcinoma (that shows cytoplasmic staining).
Abstract Category
25. Pathology
Secondary Abstract Category
5. Dermatology
Keywords
PRAME; adnexal lesions; sebaceous neoplasm; IHC; diagnostic marker
Presentation Type
Poster Presentation
PRAME Expression in Adnexal Lesions and Common Skin Cancer-Types: Biomarker with Potential Diagnostic Utility
Introduction and Objective. PRAME (PReferentially expressed Antigen in MElanoma) is a tumor-associated antigen first identified in tumor-reactive T-cell clones derived from a patient with metastatic melanoma. IHC for PRAME is useful for diagnostic purposes to support a suspected diagnosis of melanoma. Anecdotally, PRAME has been observed to stain sebaceous units in glands in background skin. We examined the expression of PRAME in adnexal lesions and common skin cancers to determine whether it is of potential diagnostic utility in distinguishing between sebaceous and non-sebaceous neoplasms. Methods. IRB approval from Mount Sinai Medical Center (MSMC) was obtained. In total, 81 patients were included: sebaceous lesions (17 cases with normal sebaceous glands, hyperplasia, heterotopia, adenoma, steatocystoma, epithelioma, carcinoma); sweat gland lesions (32 cases with hyperplasia, syringoma, hidradenoma, hidrocystoma, poroma, spiradenoma, papillary hidradenoma, and carcinoma); follicular lesions (13 cases with trichodenoma, pilomatricoma, trichilemmal cyst); basal cell carcinoma (BCC; 10 cases); squamous cell carcinoma (SCC; 9 cases). Cases from MSMC between January 01, 2012, and December 31, 2023, were included. Staining intensity was subcategorized into negative, weak, moderate, and strong, whereas expression percentage positivity into 0%, 1-25%, 26-50%, 51-75%, 76-100%. Results. We found that most sebaceous (vs. non-sebaceous) lesions exhibited positive PRAME expression (CYTOPLASMIC staining) of moderate to strong intensity in >75% of cells. PRAME has a sensitivity and specificity of 100.0% and 86.7%, respectively, for sebaceous vs. non-sebaceous adnexal lesions. Also, BCCs and SCCs show weak to moderate NUCLEAR staining for PRAME (mostly in >75% of cells). Of the 13 lesions of hair follicle origin, none expressed PRAME. Of the 32 lesions of sweat gland origin, 26 (81.25%) did NOT express PRAME while 6 (18.75%) expressed PRAME. Our observations demonstrated that the greater the maturation of sebaceous units (higher proportion of mature sebocytes), the stronger the PRAME staining is. Therefore, primitive sebocytes tend to lose PRAME, and PRAME stain diminishes towards the center of the sebaceous unit (strong at the periphery). Conclusions-Implications. We confirm the potential utility of PRAME for distinguishing (1) sebaceous from non-sebaceous adnexal neoplasms and (2) BCC and SCC (that may show nuclear staining) from sebaceous carcinoma (that shows cytoplasmic staining).