MIB1 expression in basal cell layer: a diagnostic tool to identify premalignancies of the vulva

Abstract

Lichen sclerosus, high-grade usual vulvar intraepithelial neoplasia (VIN) and differentiated VIN have a different malignant potential. The objective of this study was to quantify the proliferative activity in the basal region of the epithelium of vulvar premalignancies. Furthermore, we investigated whether MIB1 expression in the basal region of vulvar epithelium can be helpful in diagnosing differentiated VIN, which may be hard to discern from normal epithelium. MIB1 was used to immunohistochemically visualise proliferating cells within formalin-fixed, paraffin-embedded, archival tissue sections of different vulvar premalignancies (N ¼ 48) and normal vulvar epithelium (N ¼ 16). Automatic digital image analysis software was developed to quantify the proliferating fraction in different parts of the epithelium (MIB1 positivity index). MIB1 expression differed among the various vulvar premalignancies; a MIB1-negative basal cell layer was a distinct feature of normal vulvar epithelium. No MIB1-negative basal cell layer was noted in differentiated VIN or other vulvar premalignancies. Owing to this negative cell layer, the MIB1 proliferation index in normal vulvar epithelium was significantly lower than in vulvar premalignancies. In conclusion, MIB1 expression can be a helpful tool in diagnosing a premalignancy and has additional value especially to distinguish differentiated VIN neoplasia from normal vulvar epithelium, but cannot explain the differences in malignant potential.

Interobserver variability and the effect of education in the histopathological diagnosis of differentiated vulvar intraepithelial neoplasia

“…[21][22][23] The use of MIB1 can be helpful to distinguish between normal vulvar epithelium and DVIN as the basal cell layer in DVIN shows a higher proliferation index (percentage of MIB1-positive cells), than normal vulvar epithelium, where the basal cell layer often is negative for MIB1. 23 Furthermore, in DVIN a strong positive staining of the (supra)basal cell layers with p53 can be seen. Strong staining of all cell layers with p16 is suggestive for usual VIN and not for differentiated VIN.…”

High levels of p53 expression correlate with DNA aneuploidy in (pre)malignancies of the vulva

“…We have previously shown that the lower compartment of dVIN is highly proliferative [26], which also contributes to increased DNA content in this study. Therefore, we have analyzed MIB1 expression in the 6 solitary dVIN lesions and found a mean percentage of positive cells of 43.1% (95% confidence interval, 18.1%-68.1%) in the basal compartment compared with 2.1% (95% confidence interval, 1.1%-4.8%) in the superficial compartment.…”

Vulvar intraepithelial neoplasia and vulvar squamous cell carcinoma: a clinicopathologic study of 18 cases

“…In addition, there is increase in the risk of squamous neoplasia, particularly of cervix and other parts of lower genital tract. The patients in this group appear to have a better prognosis than the group of patients with ISCC unrelated to HPV [1,2,9].…”

“…The first group is the type seen in young age groups (35-65 years old) and is associated with HPV, and the second group is the type seen mostly in older women (55-85 years old), is unrelated to HPV, and has different etiological factors [1,2,9].…”