Peter B. McCulloch

Measurement of carcinoembryonic antigen in patients with bronchogenic carcinoma

Estimation of CEA levels by the Z‐gel method indicates that smokers, patients with limited lung cancer and patients with extensive lung cancer have higher values than nonsmoking controls. The CEA levels within each group are significantly different from one another. Use of CEA estimation for diagnostic purposes is limited because of the considerable overlap between normal controls and patients with cancer, the relatively low incidence of elevated values in patients with limited disease and the high incidence of false negatives (20%) even in patients with extensive disease. Elevated CEA values are associated with a poor prognosis and could be of clinical value as an addition to clinical staging to determine survival particularly for patients with extrathoracic disease. Persistently high values in patients deemed clinically disease‐free postoperatively are indicative of residual disease and a poor prognosis. If and when effective therapy for bronchogenic carcinoma becomes available, monitoring of CEA values may be useful in some patients as an early indication of relapse. Further studies are required to determine if the extraordinarily poor prognosis associated with marked elevations of CEA may be used as an additional criterion of inoperability in such patients.

Cellular immunocompetence in melanoma: effect of extent of disease and immunotherapy.

Cell mediated immunocompetence was measured serially in 35 patients with malignant melanoma in order to determine the effect of extent of disease and prognosis as well as the influence of BCG immunotherapy on immune reactivity. Compared with normal adult controls, statistically significant lymphopenia occurred only in patients with widespread disease. Seventeen of 21 patients with negative pre-therapy PPD skin test converted to skin test positivity. PHA blastogenesis was depressed only in patients in the pre-terminal stages of their disease using optimal mitogen concentrations for stimulation. Threshold concentrations of this mitogen more clearly demonstrated a depressed responsiveness which correlated in severity with extent of disease. PPD induced blastogenesis was normal or increased in the majority of patients; however, the degree of stimulation by PPD was less in the BCG induced convertors than in those patients who were skin test positive before BCG treatment. Comparison of the pre- and post BCG assessments reveals no significant differences except in relation to PPD conversion. We conclude that using threshold concentrations of PHA, impaired responses are regularly associated with disease beyond the regional lymph nodes. Routine assessment of lymphocyte function by these parameters did not provide information that was not available from clinical evaluation.

Correlation of elevated C1q binding activity and carcinoembryonic antigen levels with clinical features and prognosis in bronchogenic carcinoma

The presence of immune complexes and carcinoembryonic antigen (CEA) was investigated in 50 patients with bronchogenic carcinoma at the time of and/or following diagnostic or definitive surgery. Immune complexes were measured by the Clq binding test and CEA by the Z gel method and elevations defined as values in excess of 2 S.D. above the normal mean, ≧9.2% for C1q binding activity (C1q‐BA) and ≧5.0 ng/ml for CEA. The overall incidence of elevated values was 30.7% for C1q‐BA and 34.2% for CEA. There was a greater incidence of elevated values of C1q‐BA among patients with clinically evident disease. The differences with respect to CEA elevation were not significant due to the fact that 6 of 9 samples with elevated CEA values obtained from patients with no evident disease were in fact associated with the presence of clinically undetectable disease in these patients. Elevation of C1q‐BA and CEA beyond the immediate postoperative period was predictive of a significantly shorter median survival time. The most significant differences in survival time were seen between patients with normal values for C1q‐BA and CEA and those with elevations of one or both parameters, 6.0 vs. 19.5 months (p < 0.001). Elevation of either parameter during the immediate pre‐and postoperative period was not predictive of a poor survival. In terms of clinical application, it appears that CEA estimation had the best predictive value but that the addition of C1q‐BA measurement may provide additional prognostic information, particularly in patients who do not have elevated CEA values.

CELLULAR MORPHOLOGY OF HUMAN MALIGNANT MELANOMA IN PRIMARY CULTURE

SummaryEarly monolayer outgrowths of cells from human cutaneous malignant melanomas mostly derived from metastatic lesions were examined microscopically. Cells resembling the two dendritic types of melanoma previously described in the established lines could readily be recognized. Of 22 specimens, 14 consisted of cells with a triangular dendritic morphology, four had both triangular and elongated dendritic morphology, and one had a cuboidal morphology. The remaining three specimens showed only fibroblastic outgrowths. It is concluded that cells with a triangular dendritic morphology are either the most common type of the secondary cutaneous melanomas, or alternately the most adaptable to the present culture conditions. An association of a more favorable prognosis with the homogeneous triangular dendritic cell type is noted.

Characterization of human malignant melanoma cell lines. III. Membrane immunofluorescence reactivity with sera from patients with melanoma

SummarySeven well-characterized human malignant melanoma cell lines have been evaluated in terms of their reactivity in membrane immunofluorescence tests with sera from 48 patients with melanoma, 23 patients with other forms of cancer and 28 normal controls. There was a significantly greater degree of reactivity of melanoma sera (33.7%) than of sera of normal controls (22.2%) or of sera from patients with other forms of cancer (24.2%). The incidence of strong reactors among the melanoma patients was found to be inversely proportional to the extent of disease in the melanoma patients: Stage I, 54.5%, Stage III, 36.8% and Stage IV, 29.4%. Reactivity against non-melanoma cell lines was similar in the three subject groups and was unaffected by stage of disease in the melanoma patients. No single cell line showed preferential reactivity with melanoma sera. There was an increased overall incidence of reactivity of all three subject groups against non-pigmented cell lines.A-B-0 antigens and heterophile antigens were excluded as a cause of seropositivity. The antigen(s) was trypsin-sensitive and neuraminidase-resistant.These data suggest that long term cultures of human melanoma may contain melanoma-associated antigens which may be useful in the further study and search for melanoma-specific antigens.

Absence of melanoma specificity in the reactivity of melanoma patients' sera with cultured allogeneic melanoma cell lines

While patients with melanoma are known to produce antibodies against melanoma cells, the tumor specificity of these reactions has not been well documented. Using the sensitive mixed hemadsorption assay we have identified antibody against one or more of nine different cultured melanoma cell lines in only nine of 48 patients with melanoma. Reactivity against melanoma cell lines was seen only in females, 9/27 versus 0/21 males. The strongest melanoma reactivity was seen in sera which also contained lymphocytotoxic antibody. The reactivity was not melanoma specific because it could be removed by absorption either with pooled platelets, nonmelanoma tumor cells or in two cases, by both. We conclude that the occurrence of specific antimelanoma antibodies against common or shared surface melanoma associated antigens is an uncommon event in melanoma patients not receiving specific active immunotherapy. The clinical significance of the observed reactivity and whether it is directed against cancer associated determinants, fetal antigens, or normal tissue or histocompatibility antigens requires further study.