PTEN Status in Sporadic and Cowden Syndrome-Associated Trichilemmomas: Evaluation of Immunohistochemistry and Fluorescence In Situ Hybridization
William R Sukov, Wonwoo Shon, Michael M Wolz, Carilyn N Wieland, Lawrence E Gibson, Margot S Peters. Mayo Clinic, Rochester, MN
Background: PTEN (phosphatase and tensin homolog) acts as a tumor suppressor to negatively control cellular growth and survival via the P13K/AKT signaling pathway. Cowden syndrome (CS) is a rare autosomal dominant disorder linked to germ line mutations in PTEN. A few small case series have evaluated the level of PTEN protein expression in thyroid nodules, oral papillomas, and cutaneous trichilemmomas, and loss of PTEN immunostaining appeared to be both sensitive and specific for CS-associated lesions. However, the utility of fluorescence in situ hybridization (FISH) in determining PTEN gene status has not been studied in cutaneous trichilemmomas.
Design: Formalin-fixed, paraffin-embedded sections of 14 CS-associated and 19 sporadic trichilemmomas were immunostained for PTEN (clone 6H2.1, 1:400, Dako) using heat-induced epitope retrieval and polymer refine detection system. Appropriate controls were employed. Clinical information was obtained from our medical records. PTEN deletion status was analyzed by fluorescence in situ hybridization studies were performed using a laboratory developed PTEN eneumeration probe and commercially available centromere 10 probe (Abbott Molecular).
Results: Microscopically, all skin biopsies demonstrated typical features of trichilemmoma, characterized by superficial dermal lobules of cuboidal cells with pale eosinophilic or clear cytoplasm. The peripheral nuclear palisading and adjacent thick hyaline basement membrane were also present. Complete or heterogeneous loss of PTEN expression was observed in 13/14 (92.9 %) CS-associated trichilemmomas and in 2/19 cases (10.5 %) sporadic trichilemmomas. By FISH, 4/7 (57.1%) trichilemmomas demonstrating PTEN loss, also carried hemizygous PTEN gene deletion (3/6 CS-associated and 1/1 sporadic). Of the 18 PTEN-positive tumors, no PTEN abnormality was identified by FISH.
Conclusions: Our study shows that loss of PTEN protein expression is frequently detected in CS-associated trichilemmomas suggesting that IHC may be a useful screening test. This preliminary data also indicates that there is no significant correlation between loss of PTEN expression by IHC and PTEN gene deletion by FISH; thus another mechanism must account for PTEN inactivation. Further studies of larger sample sizes are needed to define more clearly the prevalence and significance of PTEN status in trichilemmomas.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 63, Wednesday Morning