SOX2 Amplification in Bronchial Squamous Dysplasia
Frank Schneider, Carol Sherer, Kathleen Cieply, Sanja Dacic. University of Pittsburgh Medical Center, Pittsburgh, PA
Background: SOX2 is a transcription factor hypothesized to represent a lineage-specific oncogene in squamous cell carcinoma (SCC) of the lung. It has recently been shown to be amplified in high grade squamous dysplasia found in patients without malignancy. Here we present our experience with SOX2 amplification in squamous dysplasias.
Design: Amplification of SOX2 was evaluated in paraffin sections from 14 cases containing dysplastic squamous epithelium by dual-color SOX2 fluorescence in-situ hybridization using a Spectrum Green-labeled probe RP11-286G5 (CHORI, Oakland, CA) and a Spectrum Orange-labeled, probe RP11-43F17 (CHORI). Between 15 and 65 cells were scored for each case. A SOX2 to centromer of chromosome 3 ratio of 2.0 or greater was considered amplified. There were 7 cases with mild, 1 with moderate and 4 with severe dysplasia. Two cases showed squamous metaplasia and basal cell hyperplasia, respectively, but no dysplasia. Specimens included bronchoscopic biopsies (BBx), surgical margins of cancer resections and pneumonectomies for transplant.
Results: SOX2 amplification (ratio 3.6-8.8) was detected in two surgical margins close (< 0.2 cm) to invasive SCC and one repeat BBx of a previously biopsy-proven SCC, all three showing severe dysplasia. No amplification was identified in (a) mild dysplasia found in two surgical margins far (> 1 cm) from invasive SCC (n=1) and adenocarcinoma (n=1); (b) mild dysplasia found in three BBxs from patients without accompanying lung mass; (c) mild, moderate and severe dysplasia, respectively, found in three transplant pneumonectomies; (d) mild dysplasia found in a BBx of a squamous papilloma; (e) squamous metaplasia without dysplasia found in a surgical margin 1 cm from an invasive SCC; and (f) basal cell hyperplasia found in a BBx of a patient with a distant adenocarcinoma.
Conclusions: SOX2 appears to be amplified in high grade dysplasias closely associated with invasive SCC but not in a severe dysplasia involving metaplastic epithelium in a lung explant or in low grade dysplasias. This could indicate that SOX2 amplification is a late event in squamous carcinogenesis. Its assessment in surgical margins containing dysplasia may be helpful in assessing risk for recurrence at the bronchial stump.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 293, Tuesday Morning