Download Prediction of Survival in Gynecological Cancer

[CANCER RESEARCH 40, 461 2-461 6. December 1980]
0008-5472/80/0040-OOOOS02.00
Prediction of Survival in Gynecological Cancer Based on Immunological
Tests1
Irene J. Check,2'3 Robert L. Hunter,2 Karen D. Rosenberg, and Arthur L. Herbst
Departments of Pathology ¡I.J. C., R. L. H.. K. D. R.I and Obstetrics and Gynecology ¡A.L. H.¡.University of Chicago. Chicago. Illinois
ABSTRACT
Patients with advanced cancer have a depressed immunological function. We performed a battery of tests on peripheral
blood samples from 42 patients with gynecological cancer to
determine the extent to which this depression was due to
abnormal lymphocyte function, as compared to changes in the
number of lymphoid cells in the peripheral blood or in the
efficiency of purification of cells in Ficoll:Hypaque gradients in
preparation for testing. The percentage of lymphocytes in the
gradient-derived
cell suspension (% LG) and the absolute
lymphocyte count were more informative than mitogen stimu
lation, mixed leukocyte culture, and T- and B-cell measure
ments. Both values decreased significantly with the advancing
stage of cancer, and we were able to predict survival of patients
with uniform stage of disease. The % LG correlated with
survival better than did any other test when multivariate analy
ses of all test combinations were performed. Low values of %
LG reflected both the depressed lymphocyte counts and the
altered buoyant density of the leukocytes of many patients with
advanced cancer. A large portion of the depression in other
immune function tests was statistically attributed to changes in
% LG and the lymphocyte counts. We concluded that these
two simple measurements provide valuable information about
patients with gynecological cancer.
direct measurement of the appropriate factors would provide
simpler and more reliable clinical tests. To evaluate this prob
lem, we carried out a battery of immune function tests on
patients with gynecological cancer. Total and differential blood
counts and the proportion of lymphocytes in all cell suspen
sions prepared by density gradient centrifugation were deter
mined at the same time. The results of these assays were
analyzed to assess which tests correlated with the stage and
prognosis of the patients. We found that the absolute lympho
cyte count and the proportion of lymphoid cells in the density
gradient-purified
cell suspensions predicted survival better
than did any of the subsequent tests of lymphocyte function.
MATERIALS
AND METHODS
Patient Population. Blood was obtained from 42 patients
with gynecological cancer at the Chicago Lying-in Hospital.
Twenty patients had cervical cancer (Stage I, 5 patients; Stage
II, 7 patients; Stage III, 5 patients; Stage IV, 3 patients), 13
patients had ovarian cancer (Stage I, 1 patient; Stage II, 1
patient; Stage III, 8 patients; Stage IV, 3 patients), 4 patients
had endometrial cancer (Stage I, 1 patient; Stage IV, 3 pa
tients), 4 patients had leiomyosarcoma (Stage III, 1 patient;
Stage IV, 3 patients), and 1 patient had vulvar cancer (Stage I).
The stage of disease was based on the criteria of the Interna
tional Federation of Obstetrics and Gynecology (19). The data
INTRODUCTION
are presented according to stage of Cancer at the time of
testing and with respect to survival after testing. Seventeen of
Although many investigators have found depressed immune
the patients had not had previous therapy (Stage I, 8 patients;
function in patients with advanced gynecological cancer (4,
Stage II, 5 patients; Stage III, 2 patients; and Stage IV, 2
10, 21, 28, 30), the relative value of the various assays and
patients). Two patients with Stage II cervical cancer had un
their prognostic significance for individual patients remain un
dergone radiotherapy. The other patients were being treated
certain. The extent to which the observed depression in ¡mwith the standard combination chemotherapy for their tumor
munological tests represents functional deficits has not been
type, and the blood samples were obtained just before the start
separated from that which results from variation in the numbers
of a new cycle of therapy. All tests were performed on coded
of the peripheral blood cells. In patients with cancer, the
samples without knowledge of the diagnoses. Comparisons
differential WBC counts, especially the absolute lymphocyte
were made among groups of patients with gynecological can
counts, range widely (10, 24, 30). Furthermore, most tests of
cer.
immune function require density gradient-purified cell suspen
Immunological Tests. Venous blood was drawn into sterile
sions. Since many physiological factors affect the buoyant
siliconized 20-ml vacutainer tubes containing 40 mg disodium
density of leukocytes, the composition of these cell suspen
EDTA. Total WBC and leukocyte differential counts were done
sions is quite variable, especially in patients with cancer (9,
with the Hemalog D automated differential cell analyzer (Tech11).
nicon, Tareytown, N. Y.), which utilizes cytochemistry and
If either of these factors contributes substantially to the
continuous flow analysis to count a sample of 10,000 cells
outcome of immune function assays, one might expect that
(18).
Leukocytes were separated on Ficoll and sodium diatrizoate
1Supported by Grant CA 14599 from the National Cancer Institute and by the
(Hypaque) gradients (3) as recommended by WHO (1 ). Smears
Mothers' Aid Research Fund of the Chicago Lying-in Hospital. Part of this work
of the gradient cell suspension were prepared by centrifugation
was presented at the meeting of the Federation of American Societies for
Experimental Biology in Anaheim. Calif.. April 1980.
and stained for peroxidase by the method of Kaplow (16). The
2 Present address: Department of Pathology and Laboratory Medicine. Emory
proportion of lymphocytes (peroxidase-negative cells) was cal
University Medical School. Atlanta. Ga. 30322
' To whom requests for reprints should be addressed.
culated from a total count of 200 cells. Differential counts of
Received May 27. 1980; accepted September 8. 1980.
100 parallel Wright:Giemsa-stained
slides showed that the
4612
CANCER
RESEARCH
VOL. 40
Downloaded from cancerres.aacrjournals.org on June 18, 2017. © 1980 American Association for Cancer Research.
Immunological
nonlymphoid
(peroxidase-positive)
cells were predominantly
monocytes, with increasing numbers of neutrophils, and im
mature myeloid cells in cell suspensions with the lowest pro
portions of lymphocytes. The 2 stains gave comparable lym
phocyte proportions. In healthy donors, the median percentage
of lymphocytes was 55%, with 95% of the values between 40
and 80%.
Lymphocyte stimulation assays were set up in triplicate in
flat-bottomed 96-well microtiter plates (Linbro Scientific, Inc.,
Hamden, Conn.) as described previously (20). Cells (2.5 x
105) were incubated in 200-fil cultures using Roswell Park
Memorial Institute Tissue Culture Medium 1640 (Grand Island
Biological Co., Grand Island, N. Y.) containing 7.5% heatinactivated AB-positive normal human serum. The following
final concentrations of mitogens were used: Con A,410 fig/ml,
(Grade IV; Sigma Chemical Co., St. Louis, Mo.); PWM, 1:80
(Grand Island Biological Co.); and PHA, 1:800 (DIFCO Labo
ratories, Inc., Detroit, Mich.). MLC contained 2.5 x 10s pooled
irradiated (3000 rads) cells from 3 normal unrelated donors in
place of mitogen with additional control cultures containing
medium in place of patient cells. Medium control cultures
contained patient cells but no mitogen or allogeneic cells.
The cultures were incubated at 37° in a humidified CO2
incubator (Forma Scientific, Marietta, Ohio). The incubation
period was 3 days for Con A-, PWM-, and PHA-stimulated
cultures and 5 days for MLC and a second set of PWMstimulated cultures. They were then pulsed with 1 ftCi [methyl3H]thymidine (specific activity, 20 Ci/mmol; Amersham/Searle
Corp., Arlington Heights, III.) and incubated an additional 4 hr.
The cells were harvested, and radioactivity was counted as
described previously (20). The radioactivity that was incorpo
rated by medium control cultures was subtracted from that
incorporated by stimulated cultures. Their dpm (1520 ±1638,
S.D., of all 42 patients on Day 3; 1900 ± 2565 on Day 5)
showed no significant differences among patients with different
extents of disease.
We obtained 5 to 10 x 108 lymphoid cells from normal
individuals by leukopheresis and then froze them. An aliquot of
these "control cells" was thawed and tested in parallel with all
patient samples (20).
Statistics. Changes in test values with stage of disease or
tumor cell type were evaluated using analysis of variance. The
relationships between different tests were determined by the
Pearson correlation coefficients. The frequency of abnormal
results among groups of patients was assessed using contin
gency table analysis with the x2 test- Survival curves and
median survival times were determined by life table analysis
(15). The ability of the tests to predict survival was determined
by comparing the life table survival curves of groups of patients
with different test values using Lee-Desu statistics (17). The
nonparametric multivariate regression model of Cox (8) was
used to predict survival of individual patients having specified
test values. This statistical procedure uses test and survival
data from all available patients to predict the survival of a
patient with particular test values. The significance levels of the
Cox regression were calculated from the x2 values obtained by
maximizing log likelihood ratios. The coefficients (/8's) derived
4 The abbreviations used are: Con A, concanavalin A; PWM. pokeweed
mitogen; PHA, phytohemagglutinin; MLC, mixed leukocyte culture; % LG, per
centage of lymphocytes in gradient interface.
DECEMBER
1980
Tests in Gynecological
Cancer
from the Cox equation were used to calculate the magnitude of
the upward or downward shift in the survival curves expected
from a specified change in test values.
RESULTS
A battery of immunological tests was done on each of 42
patients admitted to this hospital with gynecological cancer
(Table 1). We found that the absolute lymphocyte count and
the percentage of lymphocytes in the Ficoll:Hypaque gradientpurified cell suspensions decreased most significantly in pa
tients with advanced cancer. The results of the lymphocyte
stimulation tests using mitogens or MLC also decreased with
stage of disease. The total WBC, neutrophil, and monocyte
counts and the percentages of sheep erythrocytes, active
sheep erythrocytes, or sheep erythrocytes sensitized with an
tibody and complement-rosetting lymphocytes did not change
significantly with stage of disease (data not shown). None of
these tests changed significantly with the cell type of the tumor
(data not shown). The significance levels in Table 1 are con
servative estimates since they do not take into account the
ranking of the stages.
The extent to which the depressed lymphocyte function
resulted from the depressed absolute lymphocyte counts or
% LG was evaluated by using a series of correlation analyses.
The lymphocyte stimulation data, obtained after 3 days of
culture with mitogens, correlated significantly with the total
lymphocyte count (r = 0.56, 0.54, and 0.60 for Con A, PWM,
and PHA with p values <0.001 for each) and with the values of
% LG (r = 0.53, 0.53, and 0.49 for Con A, PWM, and PHA
with p values <0.001 for each). The % LG was correlated
highly with the total lymphocyte count (r = 0.67). In view of the
large experimental errors inherent in lymphocyte stimulation
tests, these correlation values suggest that most of the depres
sion observed in 3-day stimulation tests was due to depression
in absolute lymphocyte count and % LG rather than to changes
in the capacity of individual lymphocytes to respond. The
lymphocyte stimulation data obtained after 5 days of culture
also correlated significantly with the % LG but to a lesser extent
(r values from 0.27 to 0.34).
The tests which changed with stage of disease were then
analyzed to determine if any of them had prognostic value for
individual patients. The broad range of test values in each
stage of disease is illustrated for % LG in Chart 1. We consid
ered whether test values might affect the prognosis of patients
with a particular stage of disease and evaluated this possibility
using the life table regression model of Cox (8).
Five of the tests predicted the survival of patients with ad
vanced gynecological cancer significantly better than did the
stage of disease alone, Table 2. The % LG and the Day 3 PWM
response were the most significant individual tests.
In multivariate analysis, however, only % LG retained signif
icance in all combinations. The lymphocyte count and the PWM
responses did not predict survival significantly when % LG was
factored out. This constitutes statistical evidence that % LG
measured the more basic independent parameter which pre
dicted survival of this group of patients.
The prediction of survival achieved with the combination of
% LG and the MLC response was more significant than that
achieved by either test alone, p = 0.0009. No other combina
tion of tests improved the prediction of % LG alone. This
4613
Downloaded from cancerres.aacrjournals.org on June 18, 2017. © 1980 American Association for Cancer Research.
/. J. Check et al.
Mean values (±S.D.) of blood counts and immunological
(cells/cu
of pa
mm)7620
tients881412WBC
StageIIIIIIIVPcNo.
Table 1
test results in gynecological
3)a%LG64
cancer patients grouped according to stage of cancer
stimulation tests (dpm x 10
(cells/cu
mm)2138
2484b5621
±
10341572
±
22716504
±
847923
±
43065242
±
384690
±
A164
2155±
4497±
77192±
751 ±
1338+1635
±
6866±
82127±
7886
30 ±
4078±
88127±
5888±
4440.0003Lymphocyte
±
190.004PWM-3153
±
620.01PHA224
±
30000.51Lympocytes
±
a [3HJThymidine incorporation,
370.03Con
±
65165±
7692±
921
±
5147±
06
6653±
4730±
540.01MLC86
±
610.06PWM-5147
±
310.06
±
Con A. PWM-3, and PHA assays were harvested after 3 days of culture, and PWM-5 and MLC were harvested after 5 days of
culture.
b Mean ±S.D.
c Difference among stages, analysis of variance.
IOO-
80-
o 60~
.£
S
40o.
20-
I
I
X
S
Clinical
I
ffl
I
n?
Stage at Time of Testing
Chart 1. Relation between % LG and stage of gynecological cancer. The
proportion of lymphocytes present in cell suspensions prepared by FicollrHypaque gradient separation of blood from 42 patients with gynecological cancer
is compared to the stage of cancer at time of testing. Each point represents one
patient, and the bars represent the mean values for each stage (significance of
decrease in % LG with stage is p = 0.004). Fifty-eight % of patients with Stage
III and IV disease, in contrast to 6% of patients with Stage I and II disease, had
less than 35% LG (x2 = 11.1 ; p < 0.001 ). In patients with Stage III and IV cancer,
% LG correlated with survival time (p = 0.005; Cox analysis) as in Table 2 and
Chart 2.
Table 2
Survival prediction using immunological parameters in Stage III and IV
gynecological cancer: magnitude of change in test values required for 50%
decrease in death rate multiplier
Test results of 26 patients with Stage III or IV gynecological cancer were
evaluated to determine whether the magnitude of the test values was related to
the survival times after testing. The significance of the relation between each test
and survival time (p) and the increase in test value required for a 50% decrease
in the death rate multiplier were calculated using Cox multivariate regression
analysis.
Test
Required increase in test
value
%
LGLymphocyte
countPWM-5PWM-3MLC13%407
4614
mm86,600
cells/cu
dpm35,000
dpm35.000
dpm0.0050.030.020.0050.02
suggests that the MLC test measured a parameter of lympho
cyte function with predicted survival and was not dependent
upon the % LG.
Since all but 4 of the patients with advanced cancer had
undergone some form of chemotherapy or radiotherapy, we
considered whether therapy might account for the test results.
The test results did not correlate with either the type of therapy
or the length of time from the start of therapy. For example, 2
of the patients with extremely low values of % LG (7 and 24%)
had not been treated, so that the depressed % LG values could
not have been caused by therapy. On the other hand, 2 of the
patients with over 60% LG had been diagnosed over 2 years
ago so that therapy did not necessarily depress the % LG.
To assess the potential clinical value of the statistically
significant tests, we evaluated the magnitude of the change
predicted by each test. The relative magnitude of the effects of
these tests on survival is best shown by comparing the death
rates of patients with different test values. Table 2 shows the
increase in each test value that predicts or is correlated with a
50% decrease in the death rate multiplier of patients with Stage
III and IV gynecological cancer. Although each of the tests
affected the death rate, % LG was the most sensitive test,
requiring only a 13% change for a 50% decrease in the death
rate. We also examined the magnitude of the effect of % LG by
calculating the survival curves predicted for patients with par
ticular test values. Thus, Chart 2 shows the effects of different
values of % LG on survival of patients with advanced gyneco
logical cancer. The predicted median survival time of patients
with 20% LG was only 2.6 months, while that of patients with
50% LG was greater than 9 months. The overall median survival
time for all these patients was 4.9 months.
The effect of % LG on the projected survival of individual
patients was verified by stratifying the patients into 2 groups,
those who had high (greater than 35%) and low (less than
35%) values of % LG, and comparing the Kaplan-Meier esti
mates of the survival curves within each stratum. The survival
curves were significantly different, with a median survival time
of 3.2 months for the 15 patients with less than 35% LG and
over 9 months for the 11 patients with higher values (Chart 3).
DISCUSSION
In this study, we explored the relationships among various
tests of peripheral blood cells and assessed their relative ability
to predict survival in patients with gynecological cancer.
CANCER
RESEARCH
VOL.
Downloaded from cancerres.aacrjournals.org on June 18, 2017. © 1980 American Association for Cancer Research.
40
Immunological
1.0
.9
.8
I
7
E 6
3
.5
C
o
tj
-^
o
.2-
I
23456789
Months after testing
Chart 2. Survival curves predicted for patients with Stage III or IV gynecolog
ical cancer having different values of % LG. The curves were obtained by using
the Cox analysis of test values and survival times that were observed in 26
patients with Stage III or IV disease. The significance of the relation between %
LG and survival time, p = 0.005.
> 35 % LG
P =.01
8
Months after testing
Chart 3. Kaplan-Meier life table survival curves for patients with Stage III or
IV gynecological cancer having greater than 35% LG (11 patients) or less than
35% LG (15 patients).
. survival curve for all 26 patients.
Other investigators have observed that both lymphocyte
number and results of immunological function tests correlate
with the prognosis of patients with gynecological cancer (10,
21 ). Previous workers have also reported that gradient-derived
cell suspensions from patients with cancer are frequently "con
taminated" by large numbers of nonlymphoid cells (2, 9, 11,
27).
We verified that many patients with advanced gynecological
cancer have depressed lymphocyte function. In addition, we
determined to what extent the abnormalities in lymphocyte
function tests reflect changes in the functional capacity of the
lymphocytes and to what extent they reflect differences in
absolute lymphocyte count or variations in the efficiency of
purification of the lymphoid cells used in the assays.
Each of these 3 factors contributed to the results. Primarily,
however, the results of the lymphocyte function tests in our
patients reflected the variation in lymphoid cell purification, as
DECEMBER
Tests in Gynecological
Cancer
indicated by the % LG. Both life table and Cox analysis clearly
demonstrated the predictive value of % LG in patients with
advanced gynecological cancer. To illustrate how each test
predicts survival of patients with comparable extents of dis
ease, these analyses were reported on patients with advanced
disease. Including patients with Stage I or II disease produced
results with even greater statistical significance.
The ability of % LG values to predict the survival of patients
with advanced cancer suggests that the factors which influence
the composition of the cell suspensions are fundamentally
related to the disease process. Variation in absolute lympho
cyte count among patients accounted for 45% of the variation
in % LG (r = 0.67), and changes in lymphocyte recovery
accounted for an additional 13% (r = 0.36). Increased reten
tion of the nonlymphoid cells, especially immature myeloid
cells, accounted for the remainder of the decreased % LG in
patients with advanced cancer.
The % LG did not correlate with the type of therapy, although
the number of patients in each category was too small for
statistical evaluation. We also found no relationship between
% LG and the cell type of the tumor, and we have reported
similar relationships between % LG and survival in newly di
agnosed untreated patients with lung cancer (6) and in patients
with head and neck cancer (7).
The factors that influence the sedimentation of nonlymphoid
cells in gradients need further study. Immune complexes, which
are present in the sera of some cancer patients (25, 29), may
bind to the Fc receptors on granulocytes (26) and change their
buoyant density. Other serum factors, such as cytotaxins pro
duced by endotoxin activation, alter the sedimentation prop
erties of human granulocytes and may occur in some patients
with gynecological cancer (5).
The systematic change in % LG may partially explain the
conflicting results of lymphocyte subclass determinations in
cancer patients in work reported previously (13, 23, 30). Ficoll:
Hypaque gradients are used to prepare lymphocyte-enriched
cell suspensions for nearly all immunological studies. The
interpretation of the test depends on whether lymphocytes are
distinguished from nonlymphoid cells. We performed several
rosette tests to measure lymphocyte subclasses in these pa
tients and found the same subclass composition in patients
with different stages of disease when we controlled for changes
in % LG.
We also observed that decreases in the fraction of lympho
cytes in the gradient correlated with decreased activity in
lymphocyte function tests. The tests are especially vulnerable
to the suppressive effects of macrophages and granulocytes.
These cells can inhibit lymphocyte function by producing prostaglandin E2 (12, 14) or hydrogen peroxide (22). Since a
decreased proportion of lymphocytes at the gradient interface
implies an increased percentage of suppressive cells in these
cell suspensions, changes in % LG would be expected to
correlate with decreased lymphocyte function in vitro. In fact,
the observation that patients with advanced cancer show in
creased suppressive activity in lymphocyte function assays
may primarily reflect alterations in gradient-derived cell sus
pensions. Similarly, recent findings of impaired lymphocytemediated cytotoxicity
concomitant with enhanced macrophage-mediated cytotoxicity in cancer patients might also sim
ply result from the decreased % LG (4). Comparing the results
of various functional assays before and after removing the
1980
Downloaded from cancerres.aacrjournals.org on June 18, 2017. © 1980 American Association for Cancer Research.
4615
/. J. Check et al.
nonlymphoid cells from the cell suspensions would address
this question. However, available procedures for accomplishing
this reduce the lymphocyte yield and introduce other artifacts
(1). The high correlation value between % LG and stage of
cancer supports our view that alteration in % LG is a primary
phenomenon that may reflect in vivo immune function. Altered
in vitro suppressor or cytotoxic activities may be secondary
phenomena, although they may also be biologically significant.
The relative ability of the various assays to predict survival
also supports this view. All of the lymphocyte stimulation tests
decreased in patients with advanced cancer. However, the
prognostic component of these tests primarily paralleled the
decrease in % LG. Thus, once the effect of % LG was factored
out by multivariate analysis, the MLC response, only, signifi
cantly predicted survival in advanced disease.
We have shown that the % LG is strongly related to the basic
disease process as judged by its ability to predict patient
survival. In our view, these results offer a new approach to
understanding the interaction between the immune system and
cancer. Both the WBC counts and the % LG are more funda
mental parameters than is lymphocyte stimulation, and both
are easier to measure. Achieving a better understanding of
how the cancer process affects the number of WBC and their
sedimentation behavior should shed new light on the altered
immune status of cancer patients and may tell us something
about the mechanism of cancer itself. We are currently pursu
ing these issues.
ACKNOWLEDGMENTS
We thank T. Coley. A. Matutis. and R Merker for expert technical assistance;
P. Weiser for clinical information; and T. Karrison for help with statistical analyses.
REFERENCES
1. Aiuti, F.. Cerottini, J-C.. Coombs. R. R. A., Cooper. M., Dickler. H. B..
Froland, S.. Fudenberg, H. H.. Greaves. M. F.. Grey. H. M., Kunkel. H. G..
Natvlg, J., Preud'homme. J. L. Rabellino. E.. Ritts. R. E.. Rowe. D. S.,
2.
3.
4.
5.
6.
Seligmann, M.. Slegai. F. P.. Stjernsward. J.. Terry, W. D., and Wybran. J.
International union of immunological societies report: identification, enumer
ation, and isolation of B and T lymphocytes from human peripheral blood.
Clin. Immunol. Immunopathol., 3. 584-597. 1975.
Berlinger. N. T.. Hilal, E. Y.. Oettgen, H. T., and Good, R. A. S. Deficient
cell-mediated immunity in head and neck cancer patients secondary to
autologous suppressive immune cells. Laryngoscope. 88: 470-481, 1978.
Boyum, A. Isolation of leucocytes from human blood and bone marrow.
Scand. J. Clin. Lab. Invest., 21 (Suppl. 97) 7-89. 1968.
Catalona. W. J.. Ratliff. T. L., and McCool, R. F. Discordance among cellmediated cytolytic mechanisms in cancer patients: importance of the assay
system. J. Immunol.. i 22: 1009-1014.
1979.
Catsimpoolas, N., Kurtz, S. R.. Skrabut, E. M.. and Valeri, C. E. Cytotaxins
alter the sedimentation behavior of human granulocytes. Science (Wash.
D. C.), 205. 936-937. 1979.
Check. I. J.. Hunter, R. L., Karrison, T., DeMeester. T., Golomb, H. M., and
Vardiman. J. Prognostic significance of immunologie tests in lung cancer.
4616
Clin. Exp. Immunol., in press, 1981.
7. Check. I. J.. Hunter, R. L., Lounsbury. B., Rosenberg. K., and Matz. G.
Prediction of survival in head and neck cancer based on leukocyte sedimen
tation in Ficoll-Hypaque gradients. Laryngoscope. XC: 1281-1290, 1980.
8. Cox, D. R. Regression models and life tables (with discussion). J. R. Stat.
Soc. (B), 34: 187-220, 1972.
9. Currie. G. A., Hedley. D. W., Nyholm. R. E., and Taylor, S. A. Contamination
of mononuclear cell suspensions obtained from cancer patients by the
Boyum method. Br. J. Cancer, 38. 555-556, 1978.
10. DiSaia, P. J., and Rich, W. M. Value of immune monitoring in gynecologic
cancer patients receiving immunotherapy. Am. J. Obstet. Gynecol., f35:
907-916, 1979.
11. Elhilali, M. M., Britton, S., Brosman, S.. and Fahey, J L. Critical evaluation
of lymphocyte functions in urological cancer patients. Cancer Res., 36.
132-137, 1976.
12-. Ellner, J. E.. and Spagnuolo, P. J. Suppression of antigen and mitogen
induced human T lymphocyte DMA synthesis by bacterial lipopolysacharide:
mediation by monocyte activation and production of prostaglandins. J.
Immunol.. J23. 2689-2695.
1979.
13. Fudenberg, H. H.. Wybran, J., and Robbins, D. T-rosette forming cells,
cellular immunity, and cancer. N. Engl. J. Med., 292. 475-476, 1975.
14. Goodwin. J. S.. Messner, R. P.. Bankhurst, A. D.. Peake. G. T.. Saiki. J. H..
and Williams, R. C., Jr. Prostaglandin-producing
suppressor cells in Hodgkin's disease. N. Engl. J. Med.. 297. 963-968. 1977.
15. Kaplan, E., and Meier, P. Nonparametric estimation of incomplete observa
tions. J. Am. Stat. Assoc., 53: 457-481, 1972.
16. Kaplow. L. S. Simplified myeloperoxidase stain using benzidine dihydrochloride. Blood. 26. 215-219, 1965.
17. Lee, E., and Desu, M. A computer program for comparing K samples with
right-censored data. Comput. Programs Biomed., 2. 315-321, 1972.
18. Mansberg, H. P.. Saunders, A. M., and Groner, W. The hemalog D white cell
differential system. J. Histochem. Cytochem., 22: 711-724, 1974.
19. Manual for Staging of Cancer, pp. 89-100. Chicago: American Joint Com
mittee. 1978.
20. Merker, R., Check, I., and Hunter, R. L. Use of cryopreserved cells in quality
control of human lymphocyte assays: analysis of variation and limits of
reproducibility in long-term replicate studies. Clin. Exp. Immunol., 38. 116126. 1979.
21. Nalick, R. H., DiSaia, P. J.. Rea, T. H., and Morrow, C. P. Immunocompetence and prognosis in patients with gynecologic cancer. Gynecol. Oncol..
2. 81-92. 1974.
22. Nathan, C. F., Silverstein, S. C., Brukner, L. H., and Cohn, Z. A. Extracellular
cytolysis by activated macrophages and granulocytes. II. Hydrogen peroxide
as a mediator of cytotoxicity. J. Exp. Med., 149. 100-113, 1979.
23. Nemoto, T., Han, T., Minowada, J., Angkur, V.. Chamberlain. A., and Dao.
T. L. Cell-mediated immune status of breast cancer patients: evaluation by
skin tests, lymphocyte stimulation, and counts of rosette-forming cells. J.
Nati. Cancer Inst., 53: 641-645, 1974.
24. Riesco. A. Five-year cancer cure: relation to total amount of peripheral
lymphocytes and neutrophils. Cancer (Phila.). 25. 135-140, 1970.
25. Rossen. R. D.. Reisberg. M. A.. Hersh. E. M., and Gutterman. J. U. The Clq
binding test for soluble immune complexes: clinical correlations obtained in
patients with cancer. J. Nati. Cancer Inst., 58. 1205-1215,
1977.
26. Shevach, E. M., Jaffe. E. S.. and Green, I. Receptors for complement and
immunoglobulin on human and animal lymphoid cells. Transplant. Rev.. Õ6.
3-28, 1973.
27. Sibbitt, W. J., Jr., Bankhurst. A. D., and Williams, R. C., Jr. Studies of cell
subpopulations mediating mitogen hyporesponsiveness
in patients with
Hodgkin's disease. J. Clin. Invest.. 6): 51-63, 1978.
28. Takasugi, M., Ramseyer, A., and Takasugi, J. Decline of natural nonselective
cell-mediated cytotoxicity in patients with tumor progression. Cancer Res.,
37. 413-418. 1977.
29. Theofilopoulos, A. N.. Andrews. B. S., Urist. M. M., Morton, D. L., and Dixon.
F. J. The nature of immune complexes in human cancer sera. J. Immunol.,
Õ79. 657-663. 1977.
30. Wanebo, H. J. Immunologie testing as a guide to cancer management. Surg.
Clin. N. Am., 59: 323-347, 1979.
CANCER
RESEARCH
Downloaded from cancerres.aacrjournals.org on June 18, 2017. © 1980 American Association for Cancer Research.
VOL. 40
Prediction of Survival in Gynecological Cancer Based on
Immunological Tests
Irene J. Check, Robert L. Hunter, Karen D. Rosenberg, et al.
Cancer Res 1980;40:4612-4616.
Updated version
E-mail alerts
Reprints and
Subscriptions
Permissions
Access the most recent version of this article at:
http://cancerres.aacrjournals.org/content/40/12/4612
Sign up to receive free email-alerts related to this article or journal.
To order reprints of this article or to subscribe to the journal, contact the AACR Publications
Department at [email protected].
To request permission to re-use all or part of this article, contact the AACR Publications
Department at [email protected].
Downloaded from cancerres.aacrjournals.org on June 18, 2017. © 1980 American Association for Cancer Research.