ProEx C Is More Sensitive Than p16INK4a in Detecting HR-HPV in Problematic Squamous Lesions of the Anal Canal
R Balasubramaniam, CS Kong, J Erickson, N Pourmand, ML Welton, TA Longacre. Stanford, Stanford, CA
Background: ProEx C is a potential surrogate marker for high-risk HPV (HR-HPV) in the uterine cervix and anal canal. To date, no study has correlated ProEx C staining with the presence of HR-HPV DNA detected by PCR in clinical samples from either site. We compare ProEx C, p16INK4a and Ki-67 reactivity patterns within various anal squamous lesions and correlate these findings with the results of PCR for HR-HPV DNA in all cases.
Design: We examined 81 anal lesions [14 non-dysplastic (acrochordons, hemorrhoids), 34 low-grade SIL, borderline and atypical lesions (LSIL/AIN I/condyloma; SIL1-2), 17 high-grade SIL (HSIL/AIN II-III/CIS), and 16 invasive squamous carcinomas] from 51 patients [32 M, 19 F; average age 42.7 yrs] to determine the pattern of ProEx C (Tripath Imaging Inc), p16INK4a (CINtec, mtm Laboratories) and Ki-67 (1:200, Dako) reactivity. ProEx C was scored as negative (basal staining only), focal (less than 1/2 of mucosa), or diffuse (greater than 1/2 of mucosa). p16INK4a was scored as negative (blush or strong in less than 5%), focal (strong in 5-80%) or diffuse (strong in greater than 80%). Ki-67 was scored positive when staining the upper 2/3 of mucosa. PCR for HR-HPV DNA was performed in all cases; pyrosequencing was completed on a subset of positive cases.
Results: ProEx C and p16INK4a were equally sensitive in detecting HR-HPV within invasive carcinomas and HSIL. In contrast, p16INK4a failed to stain 12 of 25 HR-HPV (PCR-positive) cases within the LSIL/borderline/atypical group. ProEx C was negative in only 1/25 of these cases. 14/14 non-dysplastic lesions were negative for ProEx C, p16INK4a and Ki-67, and no HPV DNA was detected.
Conclusions: This is the first study to compare ProEx C staining with the presence of HR-HPV DNA detected by PCR in either the uterine cervix or anal canal. Our results indicate that HR-HPV (most commonly HPV16) is present in the majority of high-grade lesions (invasive carcinomas, dysplasias) of the anal canal and a high number of anal condyloma. While both ProEx C and p16INK4a may be useful in the diagnosis of high-grade lesions of the anal canal, ProEx C was markedly more sensitive than p16INK4a in detecting HR-HPV within the problematic low-grade and borderline lesions.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 85, Wednesday Morning