The Stem Cell Associated Transcription Factor Sox2 as a Diagnostic Marker of Cervical Neoplasia
Katja Gwin, Rebecca Buell-Gutbrod, Nita Lee, Ernst Lengyel, Anthony Montag, Muhammad K Mirza. 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. Similar to other solid tumors, cervical carcinoma contains a heterogeneous population of cancer cells. Recent studies identified and characterized a cancer stem-like population from primary carcinomas of the cervix uteri by RT-PCR, and demonstrated the expression of adult stemness-related genes, including Sox2. In this study, we assed the expression of SOX2 in cervical intraepithelial neoplasia (CIN) grade I-III and invasive squamous cell carcinoma.
Design: Tissue microarrays were constructed with tissue cores from paraffin embedded biopsy material of 54 patients. Included were cases of CIN I (n=12), CIN II (n=14), CIN III (n=9), invasive squamous cell carcinoma (n=14) and normal cervix as control. The tissue microarrays were examined using immunohistochemistry for the expression and localization of Sox2. Expression of SOX2 was semi-quantitatively scored by intensity (0-3) and percentage of cells staining.
Results: In normal cervix, Sox2 was negative or expression confined to the basal cell layer of the epithelium. In low-grade dysplasia (CIN I), Sox2 positivity was seen in the basal 1/3 of the epithelium (100% of cells), mostly of moderate intensity. Cell revealing HPV associated changes usually expressed SOX2. In high-grade dysplasia, moderate to strong SOX2 expression was confined to the basal 2/3 of the epithelium in CIN II (100% of cells), and full thickness expression was seen in CIN III (100% of cells). In invasive squamous cell carcinoma, moderate to strong SOX2 expression was present in 13/14 cases (93%) in 40-100% of tumor cells. One case was negative for SOX2 expression. Squamous metaplasia and endocervical glands were devoid of SOX2 expression in all cases where they were present.
Conclusions: These findings suggest that reactivation of SOX2 is involved in the progression of cervical neoplasia and is an early step in cervical carcinogenesis. SOX2 is a useful marker for detecting cervical dysplasia on biopsy specimens. In addition, SOX2 is helpful for accurate grading of the dysplastic changes. All cases included in this study could be classified, without difficulty, as high-grade or low grade dysplasia based on the staining pattern. SOX2 however is not a suitable marker to distinguish high-grade dysplasia from invasive squamous cell carcinoma, as both reveal strong expression of this marker.
Category: Gynecologic & Obstetrics
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 121, Tuesday Afternoon