Expression of the Stem Cell Associated Transcription Factor SOX2 in Squamous Cell Carcinoma of the Vulva in Comparison to p16 and Ki-67
Rebecca J Wolsky, M Kamran Mirza, Anthony Montag, Katja Gwin. University of Chicago, Chicago, IL
Background: The high mobility group transcription factor SOX2 is essential for preservation of embryonic stem cell pluripotency and self-renewal of tissue specific adult stem cells. SOX2 has recently been identified as a novel major oncogene that plays a role in squamous cell carcinomas (SCCs). SOX2 has been shown to be recurrently amplified and activated in SCCs of the lung, esophagus, and oral cavity. Approximately 95% of vulvar malignancies are SCCs. Two distinct pathways of carcinogenesis in the vulva have been proposed: one related to infection with high-risk human papilloma virus (HPV), and the other independent of HPV, related to chronic inflammatory and granulomatous disorders of the vulva. The role of SOX2 expression in vulvar SCC is unknown. In this study, we compared the expression of SOX2 in vulvar SCC to the expression of the HPV-surrogate p16 and the proliferation marker Ki-67.
Design: A tissue microarray of invasive vulvar SCCs was constructed with tissue cores from paraffin embedded material of 24 patients. Normal vulva tissue was used as control. The tissue microarrays were examined using immunohistochemistry for the expression and localization of SOX2, p16, and Ki-67. Expression of SOX2 and p16 was scored by intensity (weak, moderate, strong). Ki-67 was scored by expression in percentage of cells (low: 0-29%; medium: 30-59%; high: 60-100%).
Results: In normal vulva, moderate SOX2 expression was confined to the basal one-third cell layers of the epithelium. Moderate to strong diffuse SOX2 expression was present in 15 of 17 cases (88%) of invasive SCC of the vulva. The two cases that were negative for SOX2 expression did express p16 with moderate and high intensity. Eleven of 17 (65%) cases of invasive SCC expressed p16 with moderate or strong intensity. The 6 cases that were devoid of p16 staining did however express SOX2. The proliferation marker Ki-67 demonstrated a high proliferation rate (>60%) in all cases (100%). Seven cases of vulvar SCC were lost during processing of the tissue microarray and could not be evaluated.
Conclusions: These findings suggest that, like SCC in the lung, reactivation of SOX2 is involved in the progression of vulvar SCC. In concordance with the currently proposed model of two distinct pathways of vulvar carcinogenesis, 35% of vulvar SCC cases in our study did not express the HPV-surrogate p16 and seem to be unrelated to an HPV-dependent pathway. All of these cases however did express SOX2, as did the majority of cases that also expressed p16, suggesting that SOX2 plays a role in both pathways.
Category: Gynecologic & Obstetrics
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 237, Tuesday Afternoon