PAX8 and PAX2 Expression in Endocervical Adenocarcinoma In-Situ and High-Grade Squamous Dysplasia
Abhishek Shukla, Dafydd Thomas, Michael H Roh. University of Michigan Medical School, Ann Arbor, MI
Background: The transcription factors, PAX2 and PAX8, are expressed in Mullerian glandular epithelial cells including the secretory cells of the fallopian tube and endometrial glandular epithelium. Currently, there is limited knowledge regarding the expression of PAX8 and PAX2 in neoplastic cervical squamous and glandular lesions. In-situ carcinomas of the cervix are exemplified by endocervical adenocarcinoma in-situ (AIS) and high grade squamous intraepithelial lesions (HSILs). Both AIS and HSIL present histologically as hyperchromatic crowded groups of epithelial cells displaying loss of polarity and hyperchromatic nuclei with coarse chromatin. Occasionally, small strips of neoplastic epithelium can be difficult to precisely classify as glandular or squamous. Hence, we sought to investigate the expression of PAX8 and PAX2 in AIS and HSIL.
Design: We identified 66 cases of AIS from the pathology archive. In 18 of these 66 cases, concurrent HSILs were present. Immunohistochemistry for PAX8 and PAX2 were performed and nuclear expression of these markers were examined in all cases. Semiquantitative scores with respect to staining intensity (0, negative; 1, weak; 2, moderate; 3, strong) and extent of staining (0, no staining; 1, <25% cells positive; 2, 25-50% cell positive; 3, >50% cells positive) were recorded for benign endocervical glandular epithelium as well as foci of AIS and HSIL. For each, the two scores were added for a combined score of 0 to 6. A combined score of 2 or less was considered negative whereas a combined score greater than 2 was considered positive.
Results: PAX8 positivity was observed in 64 (97%) of 66 cases of AIS. PAX2 was positive in 3 (5%) cases of AIS; PAX2 expression was lost in 63 (95%) of the 66 foci of AIS. In 62 of these 66 cases, benign endocervical glandular epithelium was present in the immunostained slides; PAX8 and PAX2 positivity was seen in 62 (100%) and 60 (97%), respectively. Seven (39%) and 0 (0%) of the 18 HSILs were positive for PAX8 and PAX2, respectively. The difference in PAX8 expression of AIS versus HSIL was statistically significant (Fisher exact test, p<0.05).
Conclusions: Immunohistochemistry for PAX2 is effective in confirming the diagnosis of AIS, as benign endocervical glandular epithelium is typically PAX2(+) whereas neoplastic endocervical glandular epithelium is usually PAX2(-). The far majority of AIS lesions and a subset of HSILs are PAX8(+). With regards to the distinction between AIS and HSIL, a PAX8(-) immunophenotype is particularly predictive of high grade squamous dysplasia.
Category: Gynecologic & Obstetrics
Tuesday, March 20, 2012 1:30 PM
Platform Session: Section B, Tuesday Afternoon