HGMA2 Is Overexpressed in Epithelial Precursor Lesions and Oral Squamous Cell Carcinoma.
Eugen C Minca, Germain Jean-Charles, Mihai Merzianu. Roswell Park Cancer Institute, Buffalo, NY; University of Rochester, NY
Background: Oral squamous cell carcinoma (OSCC) is often associated with epithelial precursor lesions (EPL), most commonly oral squamous dysplasia (OSD). OSD grading is an important but imperfect predictor of the malignant potential of various EPL. Identification of molecular markers to risk-stratify EPL and/or detect early OSCC is clinically relevant. High mobility group protein HMGA2 mediates epithelial-mesenchymal transition and tumor invasiveness of thyroid, pancreas, stomach and lung carcinomas, as well as OSCC. HMGA2 expression in EPL has not been investigated to date. We aimed to assess HMGA2 protein expression in EPL and OSCC and compare it with that in benign epithelium.
Design: The study included 69 areas present in 51 excisional samples from 48 patients, evaluated by 2 pathologists who independently graded dysplasia using WHO classification. Consensus diagnoses were grouped for statistical analysis as follows: normal mucosa, low-grade lesions (LG; mild dysplasia), high-grade lesions (HG; moderate dysplasia, severe dysplasia, carcinoma in-situ), and microinvasive carcinoma (MI). 61 additional cases of OSCC from a tissue microarray were also assessed. Only nuclear HMGA2 staining was recorded and scored independently by 2 observers by multiplying staining intensity (0-3) with the percentage of positive cells (1 for <5%, 2 for 5-50%, 3 for 51-80%, 4 for >80%). Using 8 samples of histologically uninvolved mucosa and 7 samples of oral mucosa excised from non-SCC tumors, a HMGA2 score of 6 or more was considered positive for this study. Statistical analysis was performed using chi-square test with p<0.05 for statistical significance.
Results: The 69 samples comprised areas of interest as follows: 15 normal mucosa, 11 LG, 35 HG and 8 MI. Nuclear HMGA2 expression was detected in only 1 of 15 (7%) normal mucosa samples, but in 6 of 11 (55%) LG, 21 of 35 (60%) HG, 3 of 8 (38%) MI and 47 of 61 (77%) OSCC samples. When compared with normal mucosa, HMGA2 was significantly overexpressed not only in OSCC (p<0.001), but also in LG (p=0.007) and HG (p<0.001) EPL. The borderline significance for MI (p=0.06) might be due to small sample size.
Conclusions: Our data shows that HMGA2 is overexpressed not only in OSCC, but also in LG and HG EPL and early invasive carcinoma. Overall, HMGA2 nuclear expression increased with the severity of dysplasia in EPL, and was highest in OSCC, suggesting that HMGA2 involvement in the neoplastic progression of EPL to OSCC might occur at an earlier stage than previously thought.
Category: Head & Neck
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 143, Tuesday Afternoon