SQUAMOUS CELL CARCINOMA ANTIGEN (TA-4) IN PENILE CARCINOMA K E N N E T H I. WISHNOW, M.D. DOUGLAS E. JOHNSON, M.D. HERBERT FRITSCHE, PH.D. From the Departments of Urology and Laboratory Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
ABSTRAC T--TA- 4 antigen, originally isolated from women with squamous cell carcinoma of the cervix, is elevated in the sera of patients with squamous cell carcinomas of several sites, including :esophagus, lungs, and head and neck. In this study, we compared the serum levels of TA-4 in ,normal volunteers, patients with resected penile squamous cell carcinoma, and patients with metail static penile squamous cell carcinoma. TA-4 values were elevated in 5 of 11 patients (45 %) who had :iilmetastatic disease. In 2, TA-4 was normal the first time metastasis was clinically detected but rose !ilaSthe disease progressed. Moreover, in 3 patients in w h o m serial determinations were made, serum values correlated well with disease progression and response to treatment. We conclude that values are elevated in some patients with metastatic squamous cell carcinoma of the penis and become a useful marker for monitoring response to therapy.
brigoe 1 isolated and purified antigen (TA-4)* from a paous cell carcinoma of the ng a radioimmunoassay to they found elevated serum of 25 patients with cervical '.er, but in only 1 of 55 sams (including patients with the cervix or benign gynecohealthy volunteers). Since vestigators have found eleof TA-4 in patients with [nomas of the lungs, esophaneck. ~-4 To date, there have .luating this antigen in squana of the penis. Therefore, We assayed the serum of patients with this dis! ease to see if TA-4 antigen was elevated, and if :so, whether it could serve as a useful tumor i;ii~arker. *T A-4 refers to tumor-associated antigen after four stages of ,i~}~i~urifieationfrom human cervical squamous cell carcinoma tissue.
ROLOGY
/
OCTOBER 1990
/
Material and Methods We assayed the serum of 23 patients who had been diagnosed with squamous cell carcinoma of the penis and were treated at The University of Texas M. D. Anderson Cancer Center at Houston between May 1, 1985, and December 31, 1987. Eleven of these patients had a history of squamous eell carcinoma of the penis. Each had previously received definitive treatment for the primary tumor, either an excisional biopsy or partial or total peneetomy. In addition, the majority of them had also undergone bilateral sentinel l y m p h n o d e biopsies, p e r f o r m e d as described by Cabanas. 5 These showed no evidence of tumor. At the time the serum TA-4 level was measured, all but 1 of these patients was disease-free according to physical examination, chest x-ray film, complete blood count, and blood chemistry studies that included liver function tests and determination of serum calcium level. In 1 patient who had Stage I
VOLUME XXXVI, NUMBER 4
315
squamous eell careinoma of the penis, the serum TA-4 level was measured immediately prior to partial peneetomy. This patient had no evidence of metastatic disease, and bilateral sentinel lymph node biopsies revealed no evidence of tumor. We also evaluated serum TA-4 levels in 11 patients with metastatic disease. In eaeh instance the p r i m a r y t u m o r had been reseeted previously. However, metastasis was doeumented by pathologic assessment of biopsy material at the time the serum TA-4 level was measured. Random serum samples from 17 healthy male volunteers with no history of cancer or other significant medieal diseases were used as eontrols. The Jackson system for staging penile earcinoma was used. ~ In eaeh ease, the diagnosis of squamous cell eareinoma was made by members of the pathology department after reviewing relevant pathologic material. The serum level of TA-4 was determined by evaluating random serum samples from eaeh subject; samples had been frozen at minus 70 °C until analysis. The serum TA-4 level was measured by the Abbott SCC-RAA test (Abbott Laboratories, North Chieago, IL). Eaeh speeimen was tested in duplicate. We eonsidered values below 3 ng/mL normal; any higher values were considered positive. Results The mean serum level of TA-4 in the 17 controls was 1.2 ng/mL (median 1.0 ng/mL, range 0.7 to 2.9 ng/mL). The mean serum level of TA4 in 10 of the patients with a history of previously treated squamous cell eareinoma of the penis but no evidence of remaining disease was 1.38 ng/mL (median 1.4 ng/mL, range 0.8 to 2.3 ng/mL). There was one apparently falsepositive result in an additional patient. A Stage II squamous cell carcinoma of the penis in this patient had been treated by total peneetomy in 1977. In 1987, the TA-4 value was 10.0 ng/mL, although we found no evidence of cancer on physical examination or chest x-ray film. The TA-4 value in 1 patient with Stage I squamous cell carcinoma of the penis prior to treatment of the primary lesion (which was 2.0 em in size) was 1.5 ng/mL. The TA-4 values in the 11 patients with metastatic disease are shown by stage in Table I. Considering a value of less than 3 ng/mL to be normal, we found that the TA-4 values were elevated in 5 of 11 patients (45 % ).
316
TABLE I. TA-4 values in patients with metastatic squamous cell carcinoma* Stage
SCC (ng/mL)
III III III IV III IV III III III III III
1.9 1.7
1.0 20.9 2.7 36.0 32.4 2.4 14.7 1.5 29.0
*Mean: 13.1 _+ 14.0; median: 2.7; range: 1-36.
Comment TA-4 antigen, whieh was originally isolated from women with squamous eell earcinoma of the cervix, is elevated in the sera of patients with squamous cell carcinomas of several sites : ineluding esophagus, lungs, and head and neeL In this study we found that TA-4 is also elevated in some patients with squamous cell carcinoma of the penis. At a reeent conference concerning TA-4 antigen in squamous cell eareinoma of the h e a d , neck, and lung, Daver reported that the mean serum levels of TA-4 in 61 male and 41 female healthy volunteers was 1.33 + 0.45 n g / m L (range, 0.5-3.2 ng/mL). 7 Similarly, S a v a r y reported a mean level of 1.21 + 0.82 ng/mL (range, 0.5-2.2 ng/mL) in controls. Our results are consistent with these reported data: t h e mean level in our eontrols was 1.20 + 0.58 ng/mL (range 0.7 to 2.9 ng/mL).7 Ten of the patients had a history of p e n i l e eareinoma but had no evidenee of disease at the: time TA-4 was measured. Except for the one : apparently false-positive value of 10.0, the TA, 4 levels of these patients were normal (mean 1.4, median 1.4, range 0.8-2.3 ng/mL). The serum TA-4 values of 5 of the 11 patients (45 % ) with metastasis, however, were elevated at some time during the course of the disease. In 2 of these patients, TA-4 was normal the first time metastatic disease was clinically detected, but became significantly elevated as the disease progressed (Fig. 1, patients 1 and 2). Moreover, in the 3 patients in whom serial determinations were made, serum TA-4 values correlated correctly with the progression of the disease or the response to treatment (Fig. 1). It is too early to assess definitively the value of TA-4 antigen in the treatment of patients
UROLOGY
/
OCTOBER 1990
/
VOLUME XXXVI, NUMBER 4
FIGURE 1.
Serial determinations o] TA-4 in 3 patients correlated with progression of disease or response to treatment.
40
Inguinal Recurrence
i I t t
30
,nguine,
Recurrence
Patient 3
with squamous cell carcinoma of the penis• It appears, however, that TA-4 is elevated in some patients with metastasis and that serial determinations m a y be useful for monitoring the course of the disease. As new treatments for metastatic disease are developed, TA-4 m a y be a useful marker for monitoring patient's response to therapy. Houston, Texas 77030 (DR. WISHNOW)
Death
¢ 20
,,¢
References
I
4: t-"
Patient 1 " I |
|
Patient 2
I
10
6
Partial
--
Lung Metastasis (Chemotherapy)
Progression
•,0• -. ,,.'" (Lungs) .•,=" ••.,,Q,,"
Q°"
Responding (Lungs)
Inguinal Node
0
/
•
Resection of Recurrence
I
L
I
1
agulnal Node
I
I
I
l
I
5/85 9185 11185 5•86 6/86 3•87 10187 11187 1188
/
OCTOBER 1990
/
1, Kato H, and Torigoe T: Radioimmunoassay for tumor antigen of human cervical squamous cell carcinoma, Cancer 40:1621 (1977). 2. Masuoka T, et ah Measurement of SCC antigen in squamous cell carcinoma of the lung, Jpn J Cancer Clin 31:914 (1985). 3. Matsurbara Y, et ah SCC antigen in patients with lung cancer, J Jpn Soe Cancer Ther 21:1036 (1986). 4. Fukunaga M, et al: Clinical study on the measurement of squamous cell carcinoma-related antigen, ]pn J Cancer Clin 31: 1885 (1985). 5. Cabanas RM: An approach for the treatment of penile careinoma, Cancer 39; 456 (1977). 6. Jackson SM: The treatment of carcinoma of the penis, Br J Surg 53= 38 (1966). 7. Ebert W, and Johnson JT (Eds): Tumor Markers in the Management of Squamous Cell Carcinoma of the Head, Neck, and Lungs, Abbott Park, Illinois, Exeerpta Mediea, 1987.
VOLUME XXXVI, NUMBER 4
317
ABSTRAC T--TA- 4 antigen, originally isolated from women with squamous cell carcinoma of the cervix, is elevated in the sera of patients with squamous cell carcinomas of several sites, including :esophagus, lungs, and head and neck. In this study, we compared the serum levels of TA-4 in ,normal volunteers, patients with resected penile squamous cell carcinoma, and patients with metail static penile squamous cell carcinoma. TA-4 values were elevated in 5 of 11 patients (45 %) who had :iilmetastatic disease. In 2, TA-4 was normal the first time metastasis was clinically detected but rose !ilaSthe disease progressed. Moreover, in 3 patients in w h o m serial determinations were made, serum values correlated well with disease progression and response to treatment. We conclude that values are elevated in some patients with metastatic squamous cell carcinoma of the penis and become a useful marker for monitoring response to therapy.
brigoe 1 isolated and purified antigen (TA-4)* from a paous cell carcinoma of the ng a radioimmunoassay to they found elevated serum of 25 patients with cervical '.er, but in only 1 of 55 sams (including patients with the cervix or benign gynecohealthy volunteers). Since vestigators have found eleof TA-4 in patients with [nomas of the lungs, esophaneck. ~-4 To date, there have .luating this antigen in squana of the penis. Therefore, We assayed the serum of patients with this dis! ease to see if TA-4 antigen was elevated, and if :so, whether it could serve as a useful tumor i;ii~arker. *T A-4 refers to tumor-associated antigen after four stages of ,i~}~i~urifieationfrom human cervical squamous cell carcinoma tissue.
ROLOGY
/
OCTOBER 1990
/
Material and Methods We assayed the serum of 23 patients who had been diagnosed with squamous cell carcinoma of the penis and were treated at The University of Texas M. D. Anderson Cancer Center at Houston between May 1, 1985, and December 31, 1987. Eleven of these patients had a history of squamous eell carcinoma of the penis. Each had previously received definitive treatment for the primary tumor, either an excisional biopsy or partial or total peneetomy. In addition, the majority of them had also undergone bilateral sentinel l y m p h n o d e biopsies, p e r f o r m e d as described by Cabanas. 5 These showed no evidence of tumor. At the time the serum TA-4 level was measured, all but 1 of these patients was disease-free according to physical examination, chest x-ray film, complete blood count, and blood chemistry studies that included liver function tests and determination of serum calcium level. In 1 patient who had Stage I
VOLUME XXXVI, NUMBER 4
315
squamous eell careinoma of the penis, the serum TA-4 level was measured immediately prior to partial peneetomy. This patient had no evidence of metastatic disease, and bilateral sentinel lymph node biopsies revealed no evidence of tumor. We also evaluated serum TA-4 levels in 11 patients with metastatic disease. In eaeh instance the p r i m a r y t u m o r had been reseeted previously. However, metastasis was doeumented by pathologic assessment of biopsy material at the time the serum TA-4 level was measured. Random serum samples from 17 healthy male volunteers with no history of cancer or other significant medieal diseases were used as eontrols. The Jackson system for staging penile earcinoma was used. ~ In eaeh ease, the diagnosis of squamous cell eareinoma was made by members of the pathology department after reviewing relevant pathologic material. The serum level of TA-4 was determined by evaluating random serum samples from eaeh subject; samples had been frozen at minus 70 °C until analysis. The serum TA-4 level was measured by the Abbott SCC-RAA test (Abbott Laboratories, North Chieago, IL). Eaeh speeimen was tested in duplicate. We eonsidered values below 3 ng/mL normal; any higher values were considered positive. Results The mean serum level of TA-4 in the 17 controls was 1.2 ng/mL (median 1.0 ng/mL, range 0.7 to 2.9 ng/mL). The mean serum level of TA4 in 10 of the patients with a history of previously treated squamous cell eareinoma of the penis but no evidence of remaining disease was 1.38 ng/mL (median 1.4 ng/mL, range 0.8 to 2.3 ng/mL). There was one apparently falsepositive result in an additional patient. A Stage II squamous cell carcinoma of the penis in this patient had been treated by total peneetomy in 1977. In 1987, the TA-4 value was 10.0 ng/mL, although we found no evidence of cancer on physical examination or chest x-ray film. The TA-4 value in 1 patient with Stage I squamous cell carcinoma of the penis prior to treatment of the primary lesion (which was 2.0 em in size) was 1.5 ng/mL. The TA-4 values in the 11 patients with metastatic disease are shown by stage in Table I. Considering a value of less than 3 ng/mL to be normal, we found that the TA-4 values were elevated in 5 of 11 patients (45 % ).
316
TABLE I. TA-4 values in patients with metastatic squamous cell carcinoma* Stage
SCC (ng/mL)
III III III IV III IV III III III III III
1.9 1.7
1.0 20.9 2.7 36.0 32.4 2.4 14.7 1.5 29.0
*Mean: 13.1 _+ 14.0; median: 2.7; range: 1-36.
Comment TA-4 antigen, whieh was originally isolated from women with squamous eell earcinoma of the cervix, is elevated in the sera of patients with squamous cell carcinomas of several sites : ineluding esophagus, lungs, and head and neeL In this study we found that TA-4 is also elevated in some patients with squamous cell carcinoma of the penis. At a reeent conference concerning TA-4 antigen in squamous cell eareinoma of the h e a d , neck, and lung, Daver reported that the mean serum levels of TA-4 in 61 male and 41 female healthy volunteers was 1.33 + 0.45 n g / m L (range, 0.5-3.2 ng/mL). 7 Similarly, S a v a r y reported a mean level of 1.21 + 0.82 ng/mL (range, 0.5-2.2 ng/mL) in controls. Our results are consistent with these reported data: t h e mean level in our eontrols was 1.20 + 0.58 ng/mL (range 0.7 to 2.9 ng/mL).7 Ten of the patients had a history of p e n i l e eareinoma but had no evidenee of disease at the: time TA-4 was measured. Except for the one : apparently false-positive value of 10.0, the TA, 4 levels of these patients were normal (mean 1.4, median 1.4, range 0.8-2.3 ng/mL). The serum TA-4 values of 5 of the 11 patients (45 % ) with metastasis, however, were elevated at some time during the course of the disease. In 2 of these patients, TA-4 was normal the first time metastatic disease was clinically detected, but became significantly elevated as the disease progressed (Fig. 1, patients 1 and 2). Moreover, in the 3 patients in whom serial determinations were made, serum TA-4 values correlated correctly with the progression of the disease or the response to treatment (Fig. 1). It is too early to assess definitively the value of TA-4 antigen in the treatment of patients
UROLOGY
/
OCTOBER 1990
/
VOLUME XXXVI, NUMBER 4
FIGURE 1.
Serial determinations o] TA-4 in 3 patients correlated with progression of disease or response to treatment.
40
Inguinal Recurrence
i I t t
30
,nguine,
Recurrence
Patient 3
with squamous cell carcinoma of the penis• It appears, however, that TA-4 is elevated in some patients with metastasis and that serial determinations m a y be useful for monitoring the course of the disease. As new treatments for metastatic disease are developed, TA-4 m a y be a useful marker for monitoring patient's response to therapy. Houston, Texas 77030 (DR. WISHNOW)
Death
¢ 20
,,¢
References
I
4: t-"
Patient 1 " I |
|
Patient 2
I
10
6
Partial
--
Lung Metastasis (Chemotherapy)
Progression
•,0• -. ,,.'" (Lungs) .•,=" ••.,,Q,,"
Q°"
Responding (Lungs)
Inguinal Node
0
/
•
Resection of Recurrence
I
L
I
1
agulnal Node
I
I
I
l
I
5/85 9185 11185 5•86 6/86 3•87 10187 11187 1188
/
OCTOBER 1990
/
1, Kato H, and Torigoe T: Radioimmunoassay for tumor antigen of human cervical squamous cell carcinoma, Cancer 40:1621 (1977). 2. Masuoka T, et ah Measurement of SCC antigen in squamous cell carcinoma of the lung, Jpn J Cancer Clin 31:914 (1985). 3. Matsurbara Y, et ah SCC antigen in patients with lung cancer, J Jpn Soe Cancer Ther 21:1036 (1986). 4. Fukunaga M, et al: Clinical study on the measurement of squamous cell carcinoma-related antigen, ]pn J Cancer Clin 31: 1885 (1985). 5. Cabanas RM: An approach for the treatment of penile careinoma, Cancer 39; 456 (1977). 6. Jackson SM: The treatment of carcinoma of the penis, Br J Surg 53= 38 (1966). 7. Ebert W, and Johnson JT (Eds): Tumor Markers in the Management of Squamous Cell Carcinoma of the Head, Neck, and Lungs, Abbott Park, Illinois, Exeerpta Mediea, 1987.
VOLUME XXXVI, NUMBER 4
317
