Association between Stromal Myofibroblasts and Molecular, Clinical, and Histopathological Features of Premalignant and Malignant Lip Lesions
Maria L Spencer, Paulina Zapata, Alejandra Martinez, Natalia Riquelme, Ornella Salvatori, Isolde G Rojas. College of Dentistry, University of Concepcion, Concepcion, Chile
Background: Tumor stroma composition is an important prognostic factor in several neoplasias. An increased density of stromal myofibroblasts is associated with higher tumor aggressiveness and mortality in oral squamous cell carcinoma (SCC). Lip SCC is a type of oral cancer characterized by altered p53 and COX-2 expression as well as by an activated stroma both in its premalignant and malignant stages, and includes increased angiogenesis, inflammatory infiltration and fibroblast density. Since myofibroblasts have not been characterized during lip carcinogenesis, the aim of this study was to assess myofibroblast density and its association with molecular and clinicopathological features of both the premalignant lip lesion, actinic cheilitis (AC) and lip SCC.
Design: Sixty two AC samples (11 with dysplasia) and 54 lip SCC samples were processed for immunohistochemical detection of myofibroblasts with the marker smooth muscle actin (SMA). Immunohistochemical detection of p53 and COX-2 was also performed. Samples were scored 1 if SMA+ cells corresponded only to blood vessels, 2 if SMA+ myofibroblasts were <50% of the stroma, and 3 if SMA+ myofibroblasts were >50% of the stroma. Scores (based on intensity and extension) were also obtained for p53 and COX-2 expression at the epithelial or tumor compartments of each sample.
Results: Myofibroblasts were significantly increased in lip SCC (55%) as compared to AC (13%) (P<0.0001, Fisher´s Exact test). In lip SCC samples, 44% had score 1, 24% score 2, and 31% score 3. In AC samples, 86% had score 1 and 13% score 2, with no score 3. Female patients with lip SCC showed higher stromal myofibroblast density than males (P<0.05). Myofibroblast density had no association with TNM stage or tumor differentiation, however, it was associated with epithelial dysplasia in AC (P<0.05). Stromal myofibroblast density was also associated with p53 expression both in AC and lip SCC (P<0.0001, t-test), but no association was found with COX-2 expression.
Conclusions: Myofibroblast density increases as lip cancer progresses, and it is associated with gender (higher in females) and p53 expression. This suggests that stromal myofibroblasts are important markers of malignancy during lip carcinogenesis. Supported by CONICYT Chile, grant FONDECYT 1090287.
Category: Head & Neck
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 179, Wednesday Morning