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Evaluation of plasma hCG measurement in the diagnosis of nontrophoblastic neoplasms and assessment of the value of concomitant measurement of plasma hCG and CEA in patients with bronchogenic carcinoma and neoplasms of the digestive tract were undertaken. Only one of 70 normal control subjects had positive plasma hCG (3.5 ng/ml), whereas 54 of 320 patients with nontrophoblastic neoplasms had measurable plasma hCG (1.9 to 160 ng/ml). Forty of these patients had less than 5.1 ng/ml, 10 had 5.1 to 10 ng/ml, and only three had high levels of 96,110, and 160 ng/ml. Elevated plasma CEA levels of 3.6 to 140 ng/ml were found in 38 of the 70 patients with bronchogenic carcinoma and 30 of the 72 patients with neoplasms of the digestive tract in this series. Concomitant positive hCG was found in only six of the 68 patients who had elevated CEA levels, and positive hCG was found in eight of 74 patients who had normal plasma CEA. The low frequency and the modest elevation of plasma hCG, despite frequent advanced disease, indicate plasma hCG has limited value as a biologic marker fQr diagnosis and assessment of nontrophoblastic neoplasms.

Two hundred and twenty-eight patients who were treated for carcinoma of the lung were followed a n d their plasma CEA levels assessed at intervals during the course of the disease. In addition, plasma samples were taken from 487 healthy blood donors for comparison as a control. CEA assay is not selective or specific enough, at this time, to be used for screening purposes even though 68% of the patients who have lung cancer will have a n elevated concentration of CEA regardless of the histological cell type. In patients with plasma levels of CEA above 15 ng/ml the prognosis is uniformly poor. CEA in the authors' view does have value as a prognostic marker capable of suggesting the successful resection of a tumor and to a lesser degree confirming the clinical objective response to the radiotherapy or chemotherapy. It was found that the presence of CEA was not necessarily related to the volume of the tumor or the site of organ metastasis, but reflects the metabolic properties and characteristics of the individual tumor as it occurs in the patient.

Biochemical transformation of Ltk-cells with the herpes simplex virus thymidine kinase (tk) gene resulted in numerous TK+ colonies that survived selection in hypoxanthine-aminopterin-thymidine medium. Many of these TK+ cell lines switched phenotypes and reverted to the TK-state. In this report, we describe the biological and biochemical characteristics of three TK-revertant lines. One (KjB5) transiently expressed TK in the presence of bromodeoxyuridine, which selects for the TK-phenotype. Another TK-sibling (KjB6n) expressed TK only after removal from bromodeoxyuridine-containing medium.The last variant (K1B6rn) lost the ability to switch to the TK+ phenotype, although it maintained the herpes simplex virus sequences coding for TK. Loss of the ability of KlB6mC cells to express TK was correlated with extensive methylation of the sequence recognized by the restriction endonuclease HpaII (pCpCpGpG). After these cells were treated with 5-azacytidine, they regained the ability to clone in hypoxanthine-aminopterin-thymidine medium and reexpressed virus tk mRNA and enzyme. In addition, the HpaII sites that were previously shown to be refractile to enzyme digestion were converted to a sensitive state, demonstrating that they were no longer methylated.