扁平上皮癌関連抗原 TA-4 の基礎的ならびに臨床的検討

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This paper shows the basis and clinical evaluations of a tumor-antigen TO-4 of squamous cell carcinoma. 1. Basic findings of TO-4 TO-4 was originally purified from squamous cell carcinoma of the uterine cervix. It required four steps to obtain the final product,the purified antigen was designated as "Tumor-Antigen 4(TO-4)". Recently, TO-4 was found to be divided into at least 14 subgroups by isoelectric focusing. Each fraction showed almost the same molecular weight of approximately 42,000〜48,000, and shared at least several immunologic determinants. SCC Antigen,which is now used in the commercial RIA kit(DaiNabot Co, Ltd),is the most neutral fraction of these subfractions. TO-4 subfractions were divided into two subgroups:Acidic TO-4 with pI of less than 6.25 and Neutral TO-4 with pI of 6.25 or greater. Acidic TO-4 was increased in squamous cell carcinoma tissue and appeared in the circulation of patients with squamous cell carcinoma,whereas neutral TO-4 was found in both malignant and non-malignant squamous cells,but not evident in the circulation. In vitro incubation of tumor tissue or SKG-IIIa cells(squamous cell carcinoma cell line,kindly supplied by Dr.Nozawa of Keio University) also confirmed these data that acidic TO-4,but not neutral TO-4,was released into the incubation medium. Immunohistchemistry was performed by standard ABC or PAP methods using a polyclonal antibody (ATR-15) and two monoclonal antibodies (Mab-21 and Mab-317). ATR-15 responded to both acidic and neutal TA-4. Antibody Mab-21 reacted mainly with neutal TA-4,whereas Mab-317 was specific to acidic TA-4. The results showed that neutral TA-4 was present at the intermediate layer of the normal squamous epithelium and at the most parts of squamous cell carcinoma,but acidic TA-4 was found at the peripheral part of the tumor nest which was adjacent to the surround tissue. Acidic TA-4,therefore,seems to be more relating to some malignant potential of cells. 2. Clinical evaluations of TA-4 The commercial RIA kit for TA-4 is now available,which can detect 1.5ng SCC antigen/ml of serum TA-4 activity. Since 4.7% of the control subjects,including healthy volunteers and benign gynecologic disease,showed serum SCC values of more than 20.ng/ml,the cut-off value was set at 2.0ng/ml. It should be noted that some benign pulmonary disease showed high false-positive rates of around 13%. The positive rate was 51% in cervical squamous cell carcinoma. The positive rates were particularly high in advanced stages of disease,while TA-4 was not aided to detect the early cancer. High pre-treatment serum values also indicated the wide spread tumor and poor prognosis. Changes in serum levels were rapid,and were effective for evaluate the efficacy of treatment or for monitoring the disease progress. The serial determinations of serum TA-4 was also useful to detect the recurrence of cervical cancer,particularly those appeared at the distant sites. Several trials to use TA-4 for detecting the small tumor foci included(1) a more sensitive RIA using monoclonal antibodies,(2) flow cytometric analysis of TA-4 in exfoliated cells of the uterine cervix,and (3) TA-4 analysis of cervical mucus. In conclusion,TA-4 is the protein which appears in the squamous cells,and is relating to some natures of the cell such as differentiation. Particularly,acidic TA-4 appeared to reflect some biologic changes of cells(e.g., malignant potential). Determinations of circulating TA-4 levels were highly effective for evaluating the treatment effectiveness,monitoring the disease progress,and for detecting the recurrence. Further attempts should be done to use this marker for detecting the small tumor foci.
社団法人日本産科婦人科学会の論文
1987-08-01

扁平上皮癌関連抗原 TA-4 の基礎的ならびに臨床的検討

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