IMMUNOHISTOCHEMICAL DETECTION OF METALLOTHIONEIN AND MIB1 IN UTERINE CERVICAL SQUAMOUS LESIONS

Metallothioneins (MTs) are ubiquitous low molecular weight proteins wi th 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 ce rvical squamous epithelia, cervical intraepithelial neoplasms (CINs), and invasive cervical squamous carcinomas was investigated. Immunohist ochemical staining for proliferating cells using the MIB1 antibody was also performed. In normal squamous epithelia (n = 31), positive stain ing with MT was confined to basal and parabasal cells. In cases of koi locytosis (n = 14) and CIN I (n = 10), staining was also largely confi ned 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 c ells, with staining of higher cell layers in a few cases. In the major ity of cases of CIN III (n 29), there was diffuse positive staining th roughout the full epithelial thickness and, in almost all cases, posit ive staining was present above the basal and parabasal layers. Positiv e staining was present in 19 of 21 invasive squamous carcinomas. With MIB1, positivity was confined to the parabasal layer in normal squamou s epithelia. In cases of GIN, positive cells were present in progressi vely higher cell layers, in accordance with the grade of GIN. There wa s widespread positive staining in all cases of invasive squamous carci noma. Overexpression of MT, demonstrated immunohistochemic ally, is as sociated with CIN III and invasive cervical squamous carcinoma, lesion s which exhibit the highest proliferative activity, as shown by MIBI i mmunostaining. 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.