Tissue evaluation of immune markers in endometrial and cervical carcinomas.

Major histocompatibility complex (HLA system) class II molecules including HLA-DR antigens, associate with peptides, which are derived from antigens, for presentation to T4 lymphocytes. Functional and adhesion assays have shown that CD4 molecule interacts with HLA class II molecules, leading to enhanced responses of T4 cells. In the present study, we examined the tissue expression of HLA-DR antigens and the quantitative variance of T4 lymphocytes in a series of 50 "endometrioid" adenocarcinomas of the endometrium and 35 cervical squamous-cell carcinomas. A three-step avidin-biotin immunoperoxidase staining method was applied. As primary antibodies, we used the TAL.1BS monoclonal antihuman HLA-DR alpha (alpha) chain antibody and the OPD4 mouse antihuman antibody; the latter mainly identifies benign T4 lymphocytes. Twenty-four percent (24%) of women with endometrial cancer were high immune responders, while the relative percentage in women with cervical cancer was 40%; the respective tumours were of early clinical and surgical stages. HLA-DR determinants were predominantly expressed in membranes of stromal cells, mainly histiocytes, usually around HLA-DR+ lymphoid cells, as well as on endothelial cells. Greater numbers of OPD4+ aggregated lymphocytes were observed when the tumour stroma was rich in HLA-DR+ cells. Epithelial elements, either cancerous or benign, were seldom HLA-DR+. In those samples, positive immunolabelling was often confined in the intercellular space and did not seem to activate an effective host immune response against neoplastic cells. High expression of HLA-DR molecules in professional antigen presenting stromal cells may be used as a lymphocyte activation marker in endometrial and cervical carcinomas. This activation appears to be an early event in the evolution of invasive endometrial and cervical carcinomas.

Proliferating cell nuclear antigen and heat shock protein 70 immunolocalization in invasive ductal breast cancer not otherwise specified.

A series of 80 female patients undergoing surgery for primary breast ductal infiltrating carcinoma not otherwise specified (NOS) was immunohistochemically studied in order to verify any relationships between Proliferating Cell Nuclear Antigen (PCNA) immunostaining, Heat Shock Protein 70 (HSP70) immunoreactivity, and several clinicopathological predictors. Positive PCNA scores (> 20% of strongly immunopositive malignant nuclei) were observed in neoplastic cells' nuclei in 13 tumors (16.25%) and were intimately associated with axillary nodal involvement (p = 0.0131), relatively high tumor grades (p = 0.0016), increased tumor size (p = 0.0312), and low or negative levels of estrogen receptors (p = 0.0323). HSP70 positive immunoexpression in malignant cells' cytoplasm (percentage of HSP70 immunoreactive cells > 10%) was detected in 33 samples (41.25%). It correlated significantly with presence of axillary lymph nodal metastases (p = 0.0033) and rather poor tumor differentiation (p = 0.0014), whereas an association of borderline statistical significance emerged between HSP70 immunoreactivity and high progesterone receptor status (p = 0.0637). PCNA positive immunostaining demonstrates the tumors' proliferative fraction and might be used as an indicator of increased malignant potential in breast cancer since it was associated with four adverse prognosticators. HSP70 immunodetection is a probable marker of the biological stress experienced by breast cancer cells, since it was related to relatively high tumor grades. Since both proteins may potentially predict disease outcome, their prognostic significance must be validated by direct relation to survival. A multivariate statistical analysis including the variables with which both proteins were associated will reveal any possible independent prognostic value of PCNA and HSP70 immunostaining in local, ductal invasive breast cancer NOS.

Immunohistochemical detection of oestrogen receptors in ductal carcinoma in situ of the breast.

The expression of oestrogen receptor (ER) protein in invasive carcinoma of the breast and its clinical significance has been extensively evaluated. Little information is available regarding ER expression in ductal carcinoma in situ (DCIS). In this study, 46 formalin-fixed, paraffin-embedded tissue specimens of mammographically detected DCIS were evaluated immunohistochemically for the presence of ER using specific monoclonal antibodies against ER (ER-ICA Abbott Lab). The associations between ER expression and histological type, degree of differentiation and patient menopausal status were evaluated. Positive ER staining was present in 72% of cases. Non-comedo types of DCIS were more frequently ER-positive than comedocarcinoma. ER-positive tumours were inversely correlated with the presence of nuclear pleomorphism. The incidence of ER in pre-menopausal and post-menopausal women was similar. In conclusion, ER expression is present in a considerable percentage of DCIS, and ER-positivity is associated with the degree of differentiation and non-comedo carcinoma variants.