Distinguishing between Dysplasia and Reactive Atypia in Laryngeal Mucosa: Utility of p53, Ki67, CD44 and p16 Immunohistochemistry
Parthipan Kamaleswaran, Trina Lum, Lyndal A Anderson, Ruta Gupta. University of Sydney, Sydney, Australia; Royal Prince Alfred Hospital, Sydney, Australia
Background: Dysplasia and inflammatory reactive atypia show overlapping histologic features. Distinction between these is of clinical significance and can be particularly difficult in small biopsies with procedural artefacts. This study analyses the differential immunohistochemical staining of p53, Ki67, CD44 and p16 in these entities.
Design: Laryngeal and oropharyngeal biopsies from 2004-2012 were reviewed and immunostained with p53, CD44, Ki67 and p16. All slides were independently reviewed by 2 pathologists. Descriptive statistics and crosstabulations were performed (SPSS 11.5, IL, USA).
Results: There were 121 biopsies from 64 patients (M:F 46:18, median age:73 years) including non-neoplastic entities (NN) (48%), low grade dysplasia (LGD) (13%), high grade dysplasia (HGD) (17%), HGD with foci suspicious for invasion (8%), and invasive squamous cell carcinoma (SCC) (14%). Patchy p53 staining limited to the basal cell layer was seen in 36% of NNs. 71% of LGDs showed p53 in the lower third of the mucosa and in 30% focally involved the mid-portion of the mucosa. Full thickness p53 was seen in 88% of HGDs with and without foci suspicious for malignancy. In cases suspicious for invasion, p53 highlighted the microinvasive nests. Uniform full thickness p53 staining was seen in 100% of SCC. Thus p53 immunostaining significantly correlated with presence of dysplasia and malignancy (p=0.00). Ki67 staining was seen in the basal cell layer and lower thirds of 95% of NNs and 71% of LGDs. 75% of HGDs showed suprabasal Ki67 involving either 2/3rds or the entire thickness of the mucosa. Suprabasal ki67 staining was seen in 30% of SCCs. Thus Ki67 expression was not discriminatory in LGDs and reactive atypia. However, suprabasal expression of Ki67 was frequently seen in HGDs (p=0.04). CD44 membranous staining of low to moderate intensity was seen involving the lower and mid thirds of the mucosa in 91% of NNs and 86% of LGDs. Strong, full thickness membranous staining with CD44 was seen in 38% of HGDs and 67% of SCC. Thus strong membranous full thickness CD44 staining correlated with HGD and invasive malignancy (p=0.012). Patchy, focal, nuclear and cytoplasmic immunostaining with p16 was seen in 29% of cases with LGDs and 13% of cases with HGDs. Immunostaining with p16 was not of discriminatory value (p=0.51).
Conclusions: Increased expression of p53, suprabasal staining of Ki67 and strong full thickness CD44 are of diagnostic utility in distinguishing between dysplasia and reactive atypia in morphologically difficult cases.
Category: Head & Neck
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 197, Wednesday Morning