Differentiation Of Squamous Cell Carcinoma Research Articles

PROGRESS IN RADIOIMMUNOTHERAPY OF HEAD AND NECK-CANCER (REVIEW)

There is an urgent need for an effective adjuvant systemic therapy for the treatment of patients with advanced head and neck cancer. This study shows that therapy based on the use of monoclonal antibodies (MAbs) is developing to a realistic option. A few years ago the first MAbs with specificity for squamous cell carcinoma of the head and neck (HNSCC) were produced, among which was MAb E48. In animal and patient studies, in which localization of radiolabelled MAb E48 was analysed qualitatively and quantitatively, it was demonstrated that a high percentage of the injected dose accumulated selectively in the tumour. These targeting properties, when exploited for delivery of toxic agents to the tumour, give MAb E48 potential for tumour therapy. Especially the application of MAb E48 in radioimmunotherapy (RIT) seems to be attractive due to the intrinsic radiosensitivity of HNSCC. Armed with 186-Rhenium, a radionuclide recently introduced in the field of RIT, MAb E48 IgG was shown to be highly capable of eradicating established HNSCC tumours in nude mice. Complete ablation of small HNSCC was observed in this animal model by a single bolus injection. In an effort to make MAb E48 less antigenic for human application a chimeric human/mouse MAb (cMAb) has been constructed by use of recombinant DNA techniques. This modification strongly improved the capacity of MAb E48 for mediating antibody-dependent cellular cytotoxicity (ADCC). When using this cMAb E48 for RIT of minimal residual disease it can be anticipated that ADCC activity may be supportive to irradiation, especially in the ablation of single disseminated cells or small cell aggregates. Extrapolating results obtained in nude mice to patients and taking into account the good targeting in patients, RIT with E48 IgG seems to have potential for the elimination of minimal residual disease. Based on this encouraging progress, preparations are being made to evaluate the efficacy of Re-186-labelled cMAb E48 as an adjuvant in a phase III study for the treatment of patients who are at high risk for developing distant metastases.

口腔へん平上皮癌におけるモノクローナル抗ＰＣＮＡ抗体による細胞動態の解析とその意義について

The proliferative capacity of the oral squamous cell carcinoma (SCC) was analyzed immunohistochemically using monoclonal antibody against proliferating cell nuclear antigen (PCNA.) The PCNA-positive cell was detected in all cases of formalin fixed, paraffin embedded specimen from SCC and normal epithelium. The percentage of the PCNA-positive cells in SCC ranged from 0.8% to 23. 3%, and its mean value ± S. E. was 11.2±0.98%(n=36). In oral SCC, PCNA-positive rate correlated with the differentiation and cellular atypism of SCC, while there was'nt a significant difference in the relationship with the stage of the disease and the patient's prognosis. These findings suggest that immunostaining of PCNA is a convenient and important new method by which to estimate the cellular proliferation rate of oral cancer.

Comparison of Proteinase Activities in Squamous Cell Carcinoma, Basal Cell Epithelioma, and Seborrheic Keratosis

The correlation between proteinase activities and invasive and metastatic potentials was investigated by comparing three different kinds of tumors. Extracts from tumor homogenate of 11 squamous cell carcinoma (SCC), 5 basal cell epithelioma (BCE), and 8 seborrheic keratosis (SK) were prepared in order to examine the activity of acid phosphatase and proteinases such as cathepsin B and D, type I and IV collagenase, and plasminogen activator (PA). There was no difference observed between acid phosphatase and cathepsin D activities among the three tumors. Cathepsin B and PA activities were slightly elevated in SCC. Type I collagenase activity of SCC was 9-fold higher than that of SK (p less than 0.01), and type IV collagenase was 3-fold higher per tissue DNA (p less than 0.05). Type I and IV collagenase of BCE were elevated per tissue protein but not elevated per tissue DNA. Correlation was found between the level of cell differentiation in SCC and the activities of cathepsin B, PA, and type I collagenase. Poorly differentiated SCC exhibited a tendency to have higher proteinase activities. Proteinases that showed high activities in malignant tumor homogenate may be related to the degradation of the surrounding cell matrix in addition to intracellular metabolism. Type I and IV collagenase, in cooperation with cathepsin B and PA, might play a major role in invading the dermal stroma and basement membrane.

Expression of Keratin Proteins in Deeply Invasive Basal and Squamous Cell Carcinoma: An Immunohistochemical Study

The expression of certain classes of keratin is associated with cell maturation and differentiation. During cell transformation and tumor development, the cell specificity of intermediate filament, keratin, is largely conserved. Taking advantage of this, we utilized monoclonal antikeratin immunohistochemical techniques to examine basal and squamous cell carcinomas as they became deeply invasive. Dyskeratotic keratinocytes and keratin pearls in squamous cell carcinomas (SCCs) stain with antikeratin antisera to larger keratins (65-67 Kd). At the deep tumor margins, SCCs no longer express larger keratins but retain expression of 50, 58 Kd, which are markers of keratinocytes derived from stratified squamous epithelial cells. This selective loss of expression of keratin polypeptide markers of differentiation in SCC is associated with progressively more aggressive biologic behavior as the tumor invades deeper structures such as muscle and bone. Recurrent basal cell carcinoma (BCC) which was of the nodular type when first excised, shows features of morphea-like BCC and of aggressive growth patterns at the deep invasive margin. At these deep margins, some tumors express markers of keratinization (65-67 Kd). While tumor cells retain the specificity of the intermediate filament, keratin, the individual cells express products of differentiation as measured by keratin expression independently of their cytologic atypia. At the deeper invasive margin of the tumor, the neoplastic cells synthesize keratin proteins in an unpredictable fashion.