Yolume22 Number 4 April 1990

20. 21. 22. 23.

24.

25.

Livedo racemosa

eralisata (Ehrmann) mit cerebrovaculiirer Beteiligung (Herman-Sneddon). Aktuel Dermato1 1985;11:17-21. Schriftenreihe des Bundesministers fUr Jugend, Familie und Gesundheit. Daten des Gesundheitswesens, Ausgabe 1985. Doring G. Empfringnisverhiitung. Stuttgart: Thieme, 1983, Stephens WP, Ferguson JT. Livedo reticularis and cere· brovascular disease. Postgrad Med J 1982;58:70-3. Rumpl E, Neuhofer J, PaIIua A, et al. Cerebrovascular lesions and livedo reticularis (Sneddon's syndrome): a progressive cerebrovascular disorder? J Neurol 1985;231:32430. Lewis T, Pickering GW. Observations upon maladies in which the blood supply to digits ceases intermittently or permanently, and upon bilateral gangrene of digits: observations relevant to the so called "Raynaud's disease." Clin Sci 1934;1:327-66. Allen EY, Brown GE. Raynaud's disease: a critical review of minimal requisites for diagnosis. Am J Med Sci 1932; 183-7.

26. Kaha1eh MB, Sherer GK, Le Roy Ee. Endothelial injury in scleroderma. J Exp Med 1979;149:1326-35. 27. Shanahan WR, Korn JR. Cytotoxic activity of sera from scleroderma and other connective tissue diseases: lack of cellular and disease specificity. Arthritis Rheum 1982;25: 1391-5. 28. Meyer 0, Haim T, Dryll A, et al. Vascular endothelial cell injury in progressive systemicsclerosis and other connective tissue diseases. CUn Exp Rheumato11983;1:29-34. 29. Cohen S, Johnson AR, Hurd E. Cytotoxicity of sera from patients with scleroderma. Arthritis Rheum 1983;26: 170-8. 30. Deicher HFG, Drenk F, Hoffmann G. Identmcation of an L TB 4-protein complex as evidence of endothelial cell cytotoxic activity (ECA) in progressive systemic sclerosis (PSS). Z RheumatoI1987;46:196-7. 31. Drenk F, Lubach D, Schwabe C, et aI. Endothelial cytotoxic activity (ECA) in sera of patients with livedo race· mosa generalisata (Ehrmann). Arch Dermatol Res 1987;279:415-7.

Squamous cell carcinoma antigen in patients with cutaneous disorders Bruce Campbell, MB,BS,a and Brian De'Ambrosis, MB,BSb

Brisbane, Queensland, Australia Serum levels of the tumor marker squamous cell carcinoma antigen (TA-4) were examined in patients with nonneoplastic dermatologic diseases. The majority of patients with significant disease had elevated levels of this antigen. The percentage of involved skin surface area correlated with serum squamous cell carcinoma antigen levels. Psoriasis and atopic dermatitis have different effects on squamous cell carcinoma antigen levels. Kidney failure also causes elevated levels. Squamous cell carcinoma antigen is not a reliable tumor marker in patients with squamous cell carcinoma at any site when these patients also have a cutaneous disorder that involves more than 2% of the skin surface area or when they have kidney failure. (J AM ACAD DERMATOL 1990;22:639-42.)

Squamous cell carcinoma (SeC) antigen, also known as tumor-associated antigen, or TA-4, is a protein with a molecular weight of approximately 48,000 daltons. In 1977 Kato and Torigoe1 developed a radioimmunoassay for a protein antigen ex-

From the Departments of Pathology" and Dermatology,b Princess Alexandra Hospital. Accepted for publication June 22, 1989. Reprint requests: Brian De'Ambrosis, MB,BS, Department of Dermatology, Princess Alexandra Hospital, Ipswich Rd. Wooloongabba 4102, Brisbane, Queensland, Australia.

16/1/14954

tracted from sec ofthe uterine cervix. The assay has been used primarily as a tumor marker in patients with sec of the cervix. 2- 4 Other reports examined the use of this marker in patients with sec of other sites, including the lung 5 and the head and neck. 5-7 One preliminary study 8 investigated its use in patients with sec of the skin and in a small number of patients with nonmalignant disorders of the skin. This study concluded that sce antigen levels were elevated in patients with large primary SCC of the skin and in patients with metastatic disease. sec antigen levels were stated to be within the normal limits in patients with smaller nonmetastatic sce, Bowen's disease, and other non-SeC dermatoses. 8

639

Journal of the

640

American Academy of Dermatology

Campbell and De'Ambrosis SERUM see Ag LEVEL (ng/m 1 ) 0.5

HEALTHY CONTROLS

••

.. \

ATOPIC DER"ATITIS

OTHER DISORDERS >2S SKIN AFFECTED

I~



• ••

5.0

N=56

\

I

••••

...

··1

n. •

I

..• r.· • •

"

50.0

10.0

I'e

•••

PSORIASIS

OTHER DISORDERS < 2~ SKIN AFFECTED

2.4

1.0

\

A

• •• I

••





••



N=26







N=23

N=15

y

..



••

N=19

Fig. 1. Serum see antigen levels in healthy control subjects and in four groups of patients with dermatologic disorders. Because sec antigen has been demonstrated in normal squamous epithelium~9, 10 we tested the hypothesis that sec antigen levels would be elevated in nonneoplastic disorders that affected a significant part of the surface area of the skin. PATIENTS AND METHODS

All new patients admitted to the dermatology department had blood drawn for see antigen level assay after their consent was obtained. The severity of their disease was assessed as mild, moderate, or severe, and the percentage of involved body surface area was estimated by the Lund and Browder charts. 11 sec antigen levels were determined by radioimmunoassay (Abbott Laboratories, N. Chicago, Ill.). The interassay coefficient of variation was 12.1% at sec antigen level of 3.6 ngjml and 7.4% at 9.7 ng/ml. sec antigen levels were also determined in a group of 56 healthy hospital staff members. Because one previous study reported that patients with kidney failure may have elevated see antigen leve!s,6 four patients with elevated plasma creatinine levels were excluded from the study. A separate evaluation of see antigen levels in a small group of patients with varying degrees ofkidney failure but without evidence ofskin disease Or malignancy was also made. RESULTS Fig. 1 shows data broken down into four categories for the control group and for the patients. Of the

healthy control subjects, 95% had sec antigen levels ofless than 2.4 ng/ml; this level was taken as the cutoff point between normal and abnormal levels. The majority of the patients (70%) had elevated sec antigen levels. Patients with disorders affecting more than 2% of their skin surface area were even more likely to have elevated sec antigen levels. The patients with limited areas of cutaneous involvement included individual cases of pemphigus vulgaris, endogenous dermatitis, lichen planus, cutaneous leukocytoclastic vasculitis, livedoid vasculitis, cellulitis of the leg, bacterial folliculitis, contact irritant dermatitis, and keratoacanthoma centifugum marginatum, and six patients with leg ulcers. We found a significant correlation between sec antigen levels and percentage of skin surface area involved. When all the patients' data are considered together, Pearson's correlation coefficient (r) is 0.51 (p < 2 X 10-6 ). When the two largest patient groups are considered separately, a difference is found. For patients with atopic dermatitis, the correlation between sec antigen levels (r) and the percentage of skin involvement is 0.77 (p < 2 X 10-5 ). For patients with psoriasis r = 0.44 (p < 0.03). Thus, although the degree of correlation between sec antigen levels and percentage skin involvement in both these diseases is significant, the correlation is much stronger in patients with atopic dermatitis. This can

Volume 22 Number 4 April 1990

sec antigen in skin disorders

• 40

SCC Ag (ng/ml)



20

..,..

••

.. -. ..

t

8 SCCAg

• • • • •

*

10

PSORIASIS

4





50

100

2

SKIN %

40

SCC Ag (ng/ml) 20

.

0.4

100

Fig. 2. Scatterplots show serum see antigen levels versus percentage skin area involvement for patients with psoriasis and patients with atopic dermatitis. be seen in Fig. 2, in which scatterplots of percentage antigen level are skin involvement against shown for the patients with these two dermatologic disorders. The major difference is that a group of patients with psoriasis have markedly elevated antigen levels even when a relatively small amount of the total skin area is clinically involved. Severity of skin disease without regard to the amount of skin involved showed no correlation with antigen levels. The severity of disease and the percentage of skin area involved were also multiplied to yield an index that was thought possibly to give a better measure of the pathogenicity of the disease process. This derived index had a lower correlation antigen levels than did percentage with serum skin involvement alone for the total patient group

sec

sec

see

0.8

•• • 1.2

1.6

creatinine (mmoVI)

and far patients with psoriasis or atopic dermatitis. The derived index gave the same correlation coeffi cient as percentage skin involvement alone for the group of patients with miscellaneous disorders. sec antigen levels were also measured in 19 patients with varying degrees ofkidney failure butwith no other apparent cause for an elevated see antigen level. The results are shown in Fig. 3. sec antigen levels significantly correlated with plasma creatinine levels (r = 0.71; p < 0.002), and the relationship between the two found by linear regression was as follows: sec antigen (ng/m!) = 3.8 X creatinine (mmol/L) + 0.4. w

SKIN %

sec



Fig. 3. Scatterplot shows serum sec antigen levels verSus serum creatinine levels in patients with kidney failure without evidence of skin disease or malignancy. Asterisk indicates patient with both kidney failure and psoriasis.

•50

••

I.-• .,.-

ATOPIC DERMATITIS

-

SCG Ag,,35.3 ng/ml



(ng/mJ)6



641

DISCUSSION

The high percentage of patients found to have elantigen levels may be due in part to the evated population studied, because the patients had disease severe enough to require inpatient care. Patients with comparatively mild cases of atopic dermatitis or psoriasis, however, could be expected to have elantigen levels in serum; this finding is evated likely ta be true of many other cutaneous disorders that involve more than a small area of the skin surface. A consequence of this finding is that this "tumor marker" cannot be used to monitor the treatment of in any site in patients with any ofthese skin disorders.

sec

see

see

642

Campbell and De'Ambrosis

Disorders that affected less than 2% of the skin area generally had minimal effect on the serum sec antigen levels, except for a rare variant of keratoacanthoma in a patient who had a level of 6.1 ng/ ml. This finding is in accord with the significant degree of correlation found between see antigen levels and percentage of skin surface area involved by the disease process. This general phenomenon is found when all the diseases are grouped together. Immunofluorescence studies have demonstrated see antigen to be present mainly in the intermediate layers of the squamous epithelium of the uterine cervix,9, 10 although the intracellular localization of see antigen is not well defined. Immunofluorescence studies have suggested that the antigen is in the cytoplasm rather than on the cell surface,lo and thus increased plasma levels are most likely to be due to cell death and lysis or to increase in the permeability of the cell membrane that allow escape of the antigen into the circulation. Alternatively, cutaneous diseases may lead to an increased production of see antigen by epithelial cells, similar to the increased production of acute phase reactant proteins by hepatocytes under the influence of certain cytokines. 12 The lesser degree of correlation between see antigen levels and skin involvement in psoriasis compared with atopic dermatitis may be due to differences in the pathogenesis of these diseases. Psoriasis is a disease that is known to increase the cell turnover rate in apparently clinicallyuninvolved skin as well as in the clinical lesions. 13 Variations in overall. epidermal cell kinetics may explain the poorer correlation with serum see antigen levels in this disease. The lack of correlation between disease severity and see antigen levels was not expected and may be due to the subjective clinical assessment of disease severity as a variable that is independent of the area of skin involved. The highest serum levels of sec antigen were seen in generalized atopic dermatitis with an acute exacerbation due to bacterial infection, unstable acute inflammatory psoriasis, and in erythrodermic atopic dermatitis. A common finding in the above conditions is marked erythema. The associated increased cutaneous blood supply could allow greater absorption of see antigen from the epidermis into the systemic circulation. A similar mechanism may be important in explaining the high serum sec antigen levels in psoriasis.

Journal of the American Academy of Dermatology The findings of elevated sec antigen levels in patients with kidney failure confirms that of Molina et al. 6 and contradicts assertions made by others. s The simultaneous presence of skin disease (psoriasis) and kidney failure had a synergistic effect on elevating sec antigen levels as shown by the patient denoted by an asterisk in Fig. 3. This study has demonstrated that serum see antigen levels are elevated in many patients with cutaneous disorders, particularly those diseases with an inflammatory component that affect more than 2% ofthe body surface area. sec antigen cannot be used as a tumor marker in patients with these types of dermatologic disease. We acknowledge the helpful discussions we had with Dr. Graeme L. Beardmore during the preparation of this manscript. The sec antigen kits used in this study were donated by Abbott Laboratories, North Chicago, Illinois. REFERENCES 1. Kato H, Torigoe T. Radioimmunoassay for tumor antigen of human cervical squamous cell carcinoma. Cancer 1977;40:1621-8. 2. Kato H, Miyauchi F, Morioka H, et a1. Tumor antigen of human cervical carcinoma: correlation of circulating levels with disease progress. Cancer 1979;43:585-90. 3. Kato H, Morioka H, Aramaki S, et a1. Prognostic significance of the tumor antigen TA-4 in squamous cell carcinoma of the uterine cervix. Am J Obstet Gynecol 1983;145:350-4. 4. Maruo T, Shibata K, Kimura A, et a1. Tumor-associated antigen, TA-4, in the monitoring of the effects of therapy for squamous cell carcinoma of the uterine cervix. Cancer 1985;56:302-8. 5. Mino N, lio A, Hamamoto K. Availability of tumorantigen 4as a marker of squamous cell carcinoma of the lung and other organs. Cancer 1988;62:730-4. 6. Molino R, Torres X, Filella PJ, et a1. Serum SCC antigen in patients with head and neck tumors. J Tumor Marker Oncol 1987;2:277-82. 7. Yoshimura Y, Harada T, aka M, et a!. Squamous cell carcinoma antigen in the serum of oromaxillary cancer. Int J Oral Maxillofac Surg 1988;17:49-53. 8. Yagi H, Danno K, Maraguchi Y, et a!. Significance of squamous cell carcinoma (SCC)-related antigens in cutaneous SCc. Arch Dermatol1987;123:902-6. 9. Ueda G, Inoue Y, Yamasaki M, et a1. Immunohistochemical demonstration of tumor antigen TA-4 in gynecologic tumors. lnt J Gynecol PathoI1984;3:291-8. 10. Suehiro Y, Kato H, Michihiro N, et a1. Flow cytometric analysis of tumor antigen TA-4 in cervical cytologic specimens. Cancer 1986;57:1380-4. 11. Lund ce, Browder NC. The estimation of areas of burns. Surg Gynecol Obstet 1944;79:352-8. 12. Nelson DS, Geczy CL. Lymphokines, monokines and other cytokines. Aust N Z J Med 1985;15:285-90. 13. Gelfant S, Ozawa A, Chalker DK, et a1. Circadian rhythms and differences in epidermal and dermal cell proliferation in uninvolved and involved psoriatic skin in vivo. J Invest Dermatol 1982;78:58-62.

Squamous cell carcinoma antigen in patients with cutaneous disorders.

Serum levels of the tumor marker squamous cell carcinoma antigen (TA-4) were examined in patients with nonneoplastic dermatologic diseases. The majori...
372KB Sizes 0 Downloads 0 Views