Predictive Value of Cytokeratin 7 Immunohistochemistry in Cervical Low-grade Squamous Intraepithelial Lesion as a Marker for Risk of Progression to a High-grade Lesion

Abstract

The squamocolumnar junction (SCJ) cell population of the uterine cervix is a discrete epithelial area and the putative source of the majority of high-grade squamous intraepithelial lesions (HSIL). The SCJ cells can be identified by immunohistochemical (IHC) stains including cytokeratin 7 (CK7). Others have theorized that an SCJ marker-positive low-grade squamous intraepithelial lesion (LSIL) has a higher risk for future HSIL compared with an SCJ marker-negative LSIL. This study has 2 aims: first, to refine the definition of a positive CK7 immunostaining pattern in cervical lesions, and, second, to test the hypothesis that CK7 positivity in LSIL indicates higher risk for future HSIL, with both questions addressed using a data set with consensus diagnoses. One hundred cases each of LSIL, moderate HSIL (CIN2), and severe HSIL (CIN3) were stained for CK7, with positivity defined as a diffuse cytoplasmic staining pattern (>5 to 6 contiguous cells); all others were considered negative. Using this model, 34% of CIN1, 45% of CIN2, and 60% of CIN3 were CK7 positive. With follow-up, CK7-positive LSILs were more likely to progress to HSIL compared with CK7-negative LSIL (32% vs. 11%, P=0.05), in concordance with the results of other researchers. This study simplifies cervical CK7 IHC grading into a reproducible system and supports the thesis that CK7 positivity in LSIL is associated with increased risk for future HSIL. Larger cohorts using consensus-diagnosed LSIL are needed to confirm these results before CK7 may be considered for clinical validation.