Immunohistochemical Detection of Metallothionein and MIB1 in Uterine Cervical Squamous Lesions

Metallothioneins (MTs) are ubiquitous low molecular weight proteins with a high affinity for heavy metal ions such as zinc, copper, cadmium, and platinum. Immunohistochemically detectable MT overexpression has been demonstrated in a variety of cancers, especially breast carcinoma. In this study, the immunohistochemical expression of MT in normal cervical squamous epithelia, cervical intraepithelial neoplasms (CINs), and invasive cervical squamous carcinomas was investigated. Immunohistochemical staining for proliferating cells using the MIB1 antibody was also performed. In normal squamous epithelia (n = 31), positive staining with MT was confined to basal and parabasal cells. In cases of koilocytosis (n = 14) and CIN I (n = 10), staining was also largely confined to basal and parabasal cells, with only occasional cases of CIN I exhibiting positivity within higher cell layers. Cases of CIN II (n = 14) showed positive staining largely confined to basal and parabasal cells, with staining of higher cell layers in a few cases. In the majority of cases of CIN III (n = 29), there was diffuse positive staining throughout the full epithelial thickness and, in almost all cases, positive staining was present above the basal and parabasal layers. Positive staining was present in 19 of 21 invasive squamous carcinomas. With MIB 1, positivity was confined to the parabasal layer in normal squamous epithelia. In cases of CIN, positive cells were present in progressively higher cell layers, in accordance with the grade of CIN. There was widespread positive staining in all cases of invasive squamous carcinoma. Overexpression of MT, demonstrated immunohistochemically, is associated with CIN III and invasive cervical squamous carcinoma, lesions which exhibit the highest proliferative activity, as shown by MIB1 immunostaining. MT overexpression in cervical squamous lesions appears to occur at some point along the spectrum of high grade CIN and may be related to cell proliferation.