metallothionein and Carcinoma-in-Situ

In this study we evaluated the immunohistochemical expression of metallothionein (MT) in 44 squamous cell carcinomas, 14 cases of in situ carcinoma, 47 with epithelial dysplasia, 11 papillomas and 21 cases of keratosis. The MT expression was studied in correlation with p53 protein expression and the proliferative cell nuclear antigen (PCNA). The monoclonal antibodies E9 (anti-MT), DO-7 (which reacts with a denaturation-resistant epitope in wild-type and mutant p53) and PC10 (anti-PCNA) on formalin-fixed, paraffin-embedded tissue were used employing the immunoperoxidase (ABC) method. The immunohistochemical localization of MT has shown its rather ubiquitous presence in the cytoplasm and nucleus of both benign and malignant epithelial cells. In most cases the adjacent "normal" epithelium showed low positivity in the basal portion. The mean value of metallothionein expression was 35.73 in squamous cell carcinomas, 32.21 in in situ carcinomas, 11.86 in dysplastic epithelium, 5.10 in papillomas and 3.5 in keratosis. In carcinomas, low MT expression (< 10% of neoplastic cells) was observed in 20.5% of the cases, moderate (10%-50% of neoplastic cells) in 54.5% and extensive expression (> 50% of neoplastic cells) in 25% of the cases. We did not find any statistically significant difference of MT expression between in situ and infiltrating carcinomas, while we did observe a significant difference between carcinomas and the other groups. There was a statistically significant difference in the PCNA values in both benign and malignant lesions, while no statistically significant difference was observed in p53 protein expression in the above groups. A positive correlation between MT expression and the PCNA value (p < 0.0001) in the benign and malignant groups was detected. The PCNA value was also correlated with the p53 protein expression (p = 0.001). No correlation was found between MT and p53 protein expression. In conclusion, these results suggest that the MT expression may play a role in the development of malignant disease of the larynx, from the early phase of laryngeal carcinogenesis, independently from the p53 expression. It is also possible to contribute to tumour cell growth, as determined by the PCNA score.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma in Situ; Carcinoma, Squamous Cell; Epithelial Cells; Female; Humans; Immunoenzyme Techniques; Keratosis; Laryngeal Neoplasms; Male; Metallothionein; Middle Aged; Papilloma; Precancerous Conditions; Proliferating Cell Nuclear Antigen; Tumor Suppressor Protein p53

Immunocytochemically detectable MT and p53 have been found more commonly in comedo DCIS of the breast with high-grade cytology. The aim of this study is to confirm these findings and to investigate the relationship between MT and p53 in a single large series of cases of DCIS of the breast. To this end, 127 cases of DCIS were classified histologically according to architecture, cytonuclear differentiation (grade), presence and extent of intraduct necrosis, and using the Van Nuys system. Sections were immunostained for p53 and MT (E9) using established techniques, and the extent and intensity of staining were assessed semi-quantitively. The results confirmed that there was generally more MT and p53 positivity in poorly differentiated (grade 3) DCIS with extensive necrosis and that MT expression was greater in grade 2 lesions than p53 expression. However, overall there was no statistically significant correlation between p53 and MT staining. The results indicate that MT and p53 overexpression may arise from independent mechanisms in early breast neoplasia.

Topics: Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal, Breast; Cell Transformation, Neoplastic; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Metallothionein; Necrosis; Tumor Suppressor Protein p53

The Fas receptor appears to be commonly expressed in all morphological types of epithelial laryngeal hyperplasia (HP). Fas-mediated apoptotic cell death would thus be a possible phenomenon in these lesions. We observed more anti-apoptotic bcl-2 protein in epithelia with simple HP compared to the more advanced types of HP. It is suggested that in simple HP there is not yet a need for an early selection for cell death. The observed overexpression of metallothionein (MT) in the basal layers of simple HP would also support such a theory. These basal cells are dividing, non-apoptotic cells, which have not yet been selected for death. All 20 cysteine residues in MT are involved in metal binding, interfering with the intracellular redox balance, and thereby possibly inhibiting certain apoptotic signals. MIB-1 positivity was found only in the atypical HP, CIS, and invasive carcinomas. Intuition suggests that high labelling would be associated with poor prognosis. The degree of apoptosis, evaluated by TUNEL, did not show any differences between different types of epithelia. Although TUNEL is sensitive and rather specific, we emphasise that all TUNEL positive cells have apoptotic type morphology, confirming good and appropriate use of the technique.

Topics: Apoptosis; Carcinoma in Situ; Carcinoma, Squamous Cell; Epithelium; Fas Ligand Protein; Humans; Hyperplasia; Laryngeal Diseases; Laryngeal Mucosa; Laryngeal Neoplasms; Membrane Glycoproteins; Metallothionein; Neoplasm Invasiveness; Precancerous Conditions; Proto-Oncogene Proteins c-bcl-2

In a previous study immunocytochemically detectable metallothionein (MT) expression in tumor cells of invasive duct carcinoma of the breast was shown to be associated with a more aggressive behavior and these findings have been subsequently confirmed by others. The aim of this study was to examine the prevalence and significance of MT positivity in preinvasive duct carcinoma in situ (DCIS). Fifty-five specimens of pure screen-detected DCIS were stained immunocytochemically for MT using the antibody E9. The intensity and distribution of MT staining were assessed using a semiquantitative method resulting in intensity distribution (ID) scores allowing duct by duct analysis in relation to architectural and cytological features of the DCIS. In general, myoepithelial cells around benign and malignant structures stained uniformly strongly for MT. Staining in DCIS was analyzed by architecture irrespective of cytology and by nuclear grade irrespective of architecture. The results showed that MT staining was significantly greater in comedo (ducts with necrosis) DCIS (ID = 97) compared with noncomedo (ducts without necrosis) DCIS (ID = 56) (P = .05 by Mann Whitney U statistic) and that low cytological grade (ID = 50) was associated with less MT staining than was high cytological grade (ID = 92) (P = .05 by Mann Whitney U statistic). These observations thus are consistent with the previously observed association between MT positivity and more aggressive behavior in invasive duct carcinoma of the breast.

Topics: Aged; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal, Breast; Humans; Metallothionein; Middle Aged; Neoplasm Proteins