ProExC and p16 Are of Limited Diagnostic Utility in the Classification and Grading of Dysplastic Lesions of Upper Aerodigestive Tract
Ciara Ryan, Ciaran Kennedy, James Fitzgibbon, Linda Feeley, Tara Jane Browne. Cork University Hospital, Cork, NA, Ireland
Background: Upper aerodigestive tract (UADT) malignant and premalignant squamous lesions exhibit some similarities to squamous lesions seen in the cervix. Presence of HPV in head and neck squamous cell carcinoma has been shown to to have clinical and prognostic implications. HPV surrogate markers, p16 and ProExC, are beneficial in distinguishing cervical high grade squamous intraepithelial lesions from their mimicks. The aim of our study was to evaluate the role of p16, ProExC and Ki-67 in the diagnosis and grading of dysplastic lesions of UADT thus potentially identifying those lesions most likely to progress.
Design: Formalin fixed paraffin blocks from 79 UADT biopsy cases containing a range of dysplastic and non-dysplastic squamous epithelium were retrieved from files. Sections were stained with H&E, ProExC, Ki-67 and p16. Three pathologists with a special interest in Head and Neck pathology reviewed the H&E slides and a consensus diagnosis was reached in all cases. Using the WHO classification, dysplasia was divided into low (mild) and high (moderate and severe) grade. Immunohistochemical studies were scored: ProExC and Ki-67 were considered positive when strong nuclear reactivity was seen in >50% of the thickness of the epithelium. ProExC patterns of between 25-50% of cells and Ki-67 staining <50% of cells was also recorded but not considered positive. p16 was considered positive when there was cytoplasmic/nuclear and cytoplasmic staining in >90% of the epithelial cells.
Results: There were 29 non-dysplastic cases, 22 low grade and 28 high grade dysplasia cases. Positive staining for Ki-67, ProExC and p16 was observed in 79%, 64% and 7% of high grade lesions respectively. These were negative in 98%, 98% and 100% of non high grade lesions. An additional 32% of high grade lesions showed ProExc staining in 25-50% of cells. Ki-67 demonstrated the highest test performance as it was more sensitive than ProExC for confirming the presence of high grade dysplasia with equivocal specifities, although not statistically significant in these small numbers (p>0.05). Ki-67 had the highest positive predictive value (96%). When used in panels of two, Ki-67 and ProExC had the highest sensivity and 100% positive predictive value. Ki67 and ProExC also showed high concordance (92%).
Conclusions: Ki-67 is of diagnostic utility in the segregation of low and high grade lesions in the UADT. While p16 and ProExC are well established markers in HPV related high grade lesions at other sites our study shows no diagnostic utility for these markers in the classification of UADT dysplasia.
Category: Head & Neck
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 198, Wednesday Morning