068 Differential expression of keratins during cutaneous squamous cell carcinoma progression

Abstract

Squamous cell carcinoma (SCC) is the second most frequent skin cancer after basal cell carcinoma. Actinic keratosis (AK) arises within the sun exposed skin, eventually develops SCC in situ, and invasive SCC. Cancer cells may change their phenotypes along with tumor progression. However, the change of keratin (KRT) expression during this process is not fully understood. Previous studies showed increased expression of KRT6 and KRT16 in SCC, though these keratins are found in proliferating keratinocytes as found in psoriasis, thus not cancer specific. We have previously performed laser capture microdissection on AK, in situ SCC, and invasive SCC tissues. Messenger RNA extracted form those tissues were subjected to genechip analysis. Various keratin expression was altered between AK, in situ SCC, and invasive SCC. KRTs 6A and 6B were the most highly expressed compared to normal epidermis, with increased expression as cancer progression. Whereas KRTs 2 and 10, known as markers for differentiated keratinocytes, were down regulated in SCCs compared to normal epidermis. Among differentially expressed KRTs, KRT13 was slightly but significantly elevated in AK (FCH in AK vs. epidermis; 4.12) and further increased in in situ and invasive SCC (FCHs 30.54 and 40.47, respectively). KRT19 was not differentially expressed in AK region (FCH; 1.17), but increased in in situ and invasive SCC (FCHs; 2.80 and 11.33 respectively). Interestingly, KRT9, positive for differentiated keratinocytes in palms and soles, were detected in AKs (FCH in AK vs. epidermis; 17.25) but decreased in in situ and invasive SCCs. Immunohistochemistry of KRTs 9 and 13 were examined in AK and SCC tissues, as well as BCC and seborrheic keratosis to evaluate the disease specificity. Our results suggested that KRT13 was expressed even earlier stage of this malignancy. In addition, KRT19 might be a novel marker of malignant transformation of epidermal keratinocytes and acquisition of invasion capacity.