Intestinal-Type Endocervical Adenocarcinoma In Situ (iAIS): An Immunophenotypically Distinct Subset of AIS Affecting Older Women.
Brooke E Lane, Kathriel Brister, Mary Lu, Janina Longtine, Jonathan L Hecht, Marisa R Nucci. Brigham and Women's Hospital, Boston, MA; Beth Israel Deaconess Medical Center, Boston, MA
Background: Conventional endocervical adenocarcinoma in situ (cAIS) is typically strongly and diffusely positive for p16 and has a high Ki67 index in keeping with its frequent association with high risk HPV infection. The intestinal variant of AIS (iAIS) is less common, and its relationship to HPV infection and biomarker expression has not been thoroughly studied. The purpose of this study was to evaluate the frequency and pattern of p16 and Ki67 expression and the HPV status in iAIS in comparison to cAIS.
Design: Fifty-four cases of AIS (14 iAIS, 40 cAIS) were retrieved from our archives. The age of the patient at diagnosis as well as coexisting squamous lesions were recorded. HPV DNA analysis and immunohistochemistry for p16 and Ki67 were performed on cases with available tissue.
Results: The average age at diagnosis was significantly older in iAIS (age 45) versus cAIS (age 34) (p-value = 0.005). In contrast, coexisting squamous intraepithelial lesions were more common in the cAIS than the iAIS (35%, 14/40 versus 23%, 3/13). 15/19 (79%) cAIS showed strong and diffuse staining for p16. Conversely, only 5/12 (42%) iAIS had diffuse strong positivity. 10/10 (100%) cAIS showed >75% nuclei staining for Ki67. In contrast, this degree of staining was only present in 4/11 (36%) cases of iAIS. HPV DNA analysis revealed that 6/7 (86%) of iAIS cases were positive for HPV; five were type 18 and 1 was type 33.
Conclusions: iAIS is strongly associated with HPV infection, sharing a similar pathogenesis with cAIS. However, the distinctly older age is unique, suggesting that age-related factors might influence cell differentiation in these lesions. The less intense staining for p16 and Ki-67 distinguish this variant from cAIS, and this must be taken into account when using these biomarkers to resolve problematic endocervical lesions with intestinal differentiation.
Category: Gynecologic & Obstetrics
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 214, Tuesday Morning