Altered Caspase-14 Expression in Vulvar Squamous Lesions
Camille T Elkins, Christopher M Weghorst, David E Cohn, Adrian A Suarez. The Ohio State University, Columbus, OH
Background: Caspase-14 is involved in cell differentiation of stratified squamous epithelia. Its expression is normally restricted to intermediate and upper layers, while proliferating basal and parabasal layers do not express this protein. We have previously shown that caspase-14 is absent in a subset of cervical squamous cell carcinomas and that a black raspberry extract increases caspase-14 mRNA in various cervical cell lines with and without HPV. Because black raspberry bioactives can be incorporated into topical preparations for the purpose of cancer chemoprevention strategies, we investigated the expression of caspase-14 on vulvar lesions including lichen sclerosus (LS), vulvar intraepithelial neoplasia of differentiated type (dVIN), high grade vulvar intraepithelial neoplasia of classic type (cVIN) and vulvar squamous cell carcinoma (SCC). Expression of AE1, a cytokeratin known to have a pattern of expression indicative of squamous maturation similar to caspase-14, was also determined.
Design: We identified vulvectomy specimens with LS, cVIN, dVIN and SCC from our institution's pathology files. Thirteen areas of histologically unremarkable squamous epithelium (SE) adjacent to these lesions were also examined. Cases were reviewed and selected for either incorporation into a tissue microarray (TMA), recuts for whole sections, or both. Sections were stained with commercially available antibodies to AE1 and caspase-14. The staining pattern was evaluated for each diagnostic entity. In cases that included >1 diagnosis, staining pattern was evaluated separately for each entity.
Results: 12 cases of LS, 27 cases of cVIN, 12 cases of dVIN, and 25 SCC were identified. Aberrant caspase-14 basal layer staining was seen in 5/12 (42%) LS, 8/27 (30%) cVIN, 4/12 (33%) dVIN and 2/13 (15%) SE. 6 cVIN and 4 dVIN showed either full thickness or intermediate and upper layer caspase-14 reactivity while the adjacent SCC was negative. Overall 15/25 (60%) of SCC were negative for caspase-14 including well differentiated keratinizing examples. AE1 generally mirrored caspase 14 but abnormal opposite patterns were also seen.
Conclusions: Abnormal or absent caspase-14 expression was demonstrated in subsets of LS, cVIN, dVIN, SCC and SE. Our findings provide evidence for caspase-14 being a biomarker of differentiation/progression in vulvar lesions and support further research into novel chemopreventive strategies.
Category: Gynecologic & Obstetrics
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 183, Wednesday Afternoon