Studies On The Expression Of Glutathione S-Transferases In Lung Cancers And Its Clinical Applicability

Recent epidemiological studies have shown a worldwide increase in morbidity and mortality of lung cancer, indicating efforts in prevention, diagnosis and treatment of this malignancy have not been rewarding. The search for a sensitive and reliable marker for early detection and assessment of treatment results has neither been successful. In man, glutathione S-transferases(GSTs) are a group of isozymes chiefly including three cytosolic classes named basic(α), neutral(μ) and acidic(π), the potential of which as tumor markers for diagnosis, treatment and prevention of cancer has aroused much interest in recent years due to their specific role in detoxification of carcinogens and cytotoxic drugs.In the present studies, the correlation between expressions of individual GST and lung cancers, the possible mechanism and biological significance of such expressions in lung carcinogenesis and their clinical applicability were systematically evaluated. The isozymes of GSTs from human liver(GSTs-α, μ) and placenta(π) were purified, and their corresponding poly- or mono-clonal antibodies prepared for use to investigate their expressions in patients with lung cancer, by means of (1) quantitative determination of all subunits in resected or biopsied tumor tissues in 105 cases by immunohistochemical PAP and ABC stainings, (2) localization of GST-π expression in cellular ultrastructure using immunoelectronic microscopy in 11 cases, and (3) microanalysis of total GSTs in sera of 84 patients undergoing operations with BA-ELISA immunoassay. Comparative study was done in 66 of 84 cases both before and after resection. Serial measurements of sera GSTs in 10 patients with small cell lung cancer were carried out during the course of chemotherapy to observe drug resistance of cancer cells in vivo.Results: Squamous cell carcinomas were stained positively for GSTs in 9.7% (3 / 31), for GST-μ in 6.5% (2/31) and for GST-π in 93.5% (29/31), while adenocarcinomas were in 15.2% (5/33), 6.1% (2/33) and 69.7% (22/33) respectively. The expression of GST-π weakened along with declining degrees of diffferentiation of cancer cells. Of the 16 cases of small cell carcinoma examined 14 were negative for all GST individuals, while one undifferentiated squamous cell type and one oat cell type treated with chemotherapy before operation were weakly positive for GST-π. GST-α was not detectable in all 105 cancer specimens studied. Ultrastructural localization of GST-n sites was detected mainly on lysosomes in cytoplasm and heterochromatin in nucleus of non—small cell carcinomas by transmission electronic microscopy utilizing colloidal gold labelled anti—GST—π antibody.