[1245] The Stem Cell Associated Transcription Factor SOX2 as a Diagnostic Marker of Cervical Neoplasia in Comparison to p16 and Ki-67

Rebecca J Wolsky, M Kamran Mirza, Anthony Montag, Katja Gwin. University of Chicago, Chicago, IL

Background: SOX2, a high mobility group transcription factor, is essential for preservation of embryonic stem cell pluripotency and self-renewal of tissue specific adult stem cells. SOX2 has been described as a novel major oncogene that plays a role in squamous cell carcinomas (SCCs), including cervical carcinomas. A cancer stem-like population from primary cervical carcinomas was recently identified and characterized via RT-PCR, showing the expression of adult stemness-related genes, including SOX2. In this study, we evaluated the expression and diagnostic utility of SOX2 in cervical intraepithelial neoplasia (CIN) and invasive carcinoma, compared to the more commonly used proliferation marker Ki-67, and the HPV-surrogate p16.
Design: Tissue microarrays were constructed from paraffin embedded tissue of 63 cases. Included were cases of CIN I (n=19), CIN II (n=14), CIN III (n=8), invasive SCC of the cervix (n=18), and normal cervix as control (n=4). 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 distribution pattern (basal 1/3, basal 2/3, full thickness) and intensity (weak, moderate, strong). Expression of Ki-67 was scored by localization pattern (basal 1/3, basal 2/3, full thickness) and percentage of cells (low: 0-29%; medium: 30-59%; high: 60-100%).
Results: In normal cervix, SOX2 and Ki-67 expression were confined to the basal 1/3 of the epithelium, and p16 was negative.

Cervical dysplasia and carcinoma
 CIN ICIN IICIN IIISCC
SOX2 neg2/190/140/81/18
SOX2 1/314/191/140/8NA
SOX2 2/33/1912/146/8NA
SOX2 full0/191/142/817/18 (moderate, strong)
p16 neg12/191/140/82/18
p16 1/35/191/140/8NA
p16 2/31/196/140/8NA
p16 full1/194/148/816/18
p16 upper 1/30/192/140/8NA
Ki-67 1/317/194/140/8NA
Ki-67 2/32/197/142/8NA
Ki-67 full0/193/146/818/18 (moderate, high)
1/3 = basal 1/3; 2/3 = basal 2/3; full = full thickness; NA = not applicable


Conclusions: These findings support SOX2 as a diagnostic marker for the identification and classification of low and high-grade cervical dysplasia, comparable to p16 and Ki-67. SOX2 seems to be more sensitive to detect low-grade dysplasia than p16. In CIN I, p16 was negative in 63% of cases, compared to 11% being devoid of SOX2 expression. A clear advantage of SOX2 is its easily interpretable nuclear staining in contrast to the diffuse expression of p16. Similar to p16 and Ki-67, SOX2 is not a suitable marker to distinguish high-grade dysplasia from invasion.
Category: Gynecologic & Obstetrics

Monday, March 4, 2013 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 186, Monday Morning

 

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