Ferenc Juhasz

Immunogenetic and immunologic studies of differentiated thyroid cancer

The authors have studied in detail human leukocyte antigen (HLA) association in 87 Hungarian patients with thyroid epithelial carcinoma. The authors also examined in a small group of patients, five parameters of cell‐mediated immunity and related them to HLA as well as to lymphocytic infiltration of the tumor/ normal tissue interface. HLA‐DR1 was significantly associated with thyroid carcinoma; the strongest association was in patients with follicular histologic features and DRI homozygotes were not at greater risk for thyroid cancer. The HLA‐DR3 was nonsignificantly increased in patients with papillary or mixed histologic features. The HLA‐DR1, 3 heterozygotes were highly associated with follicular carcinoma, carried no risk for papillary carcinoma, and an intermediate risk for tumors with mixed histologic features. Because of the small proportion of DR1, 3 heterozygotes in the follicular and mixed histologic group, its predictive value at the population level was low. Better predictive potential was shown for the phenotype DR1 and/or DR3. Neither metastatic disease nor age at diagnosis (<45 years) could be related to HLA phenotypes. Patients in all histologic variants showed some measure of cell‐mediated immunity compared to controls. Patients with papillary carcinoma showed an overall better response than those with tumors with follicular or mixed histology. The HLA‐DR could not be related to cell‐mediated immune response. Patients with papillary carcinoma with a good cell‐mediated immune response occurred with much lower infiltration of the tumor boundary with lymphocyte whereas the follicular carcinoma less cell‐mediated immunity was associated with dense lymphocytic infiltration, suggesting the biological relevance of lymphocytic infiltration may be different for the two histologic variants.

The relation of susceptibility to and biologic behavior of thyroid epithelial cell cancer to HLA‐DR1

Fifty‐two patients with thyroid epithelial cell cancer were studied for evidence of association with human leukocyte antigens (HLA). Twenty‐eight patients (53.8%) and 19.4% of 160 controls were HLA‐DR1‐positive, conferring a relative risk of 4.85 (x2 = 21.3, P < 0.0001). HLA‐DR1 was increased in all histologic types of thyroid cancer. Interestingly 10 of 12 patients with metastatic disease were DR1‐positive compared to 18 of 41 patients without metastases (relative risk = 6.1, x2 = 4.7, P < 0.05). This study suggests that major histocompatibility complex‐linked gene(s) determine susceptibility to and the biologic behavior of thyroid cancer. Cancer 58:52–54, 1986.

B lymphocyte subsets in Hashimoto's thyroiditis

Two B lymphocyte subsets are identified on the basis of possession or lack of a surface molecule, CD5. The CD5+ B lymphocytes synthesize autoantibodies and in the process rearrange proximal variables of immunoglobulin genes. We have here studied the proportion and absolute counts of CD5+ B lymphocytes in the peripheral blood of 31 patients with Hashimotos thyroiditis and related the findings to their HLA phenotypes and clinical features. Although the percentage and absolute number of surface immunoglobulin-positive (B) lymphocytes was comparable in patients to those in twenty controls, % CD5+ was significantly higher in the patient group (38.1 +/- 11.6 [+/- S.D.] vs. 27.9 +/- 10.1, p = 0.009). The absolute CD5+ cells (microliters) were also higher in patients with Hashimotos thyroiditis (77.90 +/- 37.50 vs. 55.1 +/- 29.8, p = 0.020). The proportion of CD5+ cells was even higher in HLA-DR3 positive patients (43.1% +/- 7.2, n = 13) compared to six DR3+ controls (26.17% +/- 9.7, p = 0.0005). The difference between DR3- patients and controls was not significant (28.6% +/- 10.5 vs. 34.4% +/- 13.0). As the CD5 molecule may be induced on activated B lymphocytes, this study suggests that Hashimotos thyroiditis is associated with an increase of activated B lymphocytes engaged in autoantibody synthesis. This defect is particularly obvious in DR3+ patients.

Special features of childhood and juvenile thyroid carcinomas

A retrospective analysis was conducted on 36 patients who underwent surgery for childhood or juvenile thyroid cancers and who were regularly followed up during the course of 30 years. The biological properties and late prognosis of these patients were assessed, and the clinical and morphological characteristics of the tumors were examined. The distribution of the DNA content in the tumor cells was compared with that in adult tumor cells, and the results of cytogenetic tests performed on mothers operated on for thyroid tumors and their children are also discussed.

535 Childhood- and juvenile thyroid carcinomas

The authors report on the late prognosis and biological properties of thyroid carcinomas in 36 patients, developed before the age of 20. All patients underwent surgical treatment and were followed up from 1962 to 1994. Papillary carcinoma was diagnosed in 30, follicular carcinoma in 4, and medullary carcinoma in 2 patients. In 11 cases cervical lymphnode excision or cytologic examination was performed before the operation, that verified the diagnosis. 24 of the 36 patients had T-2 tumors at the time of the operation. Lymph node metastasis was found in 21, lung metastasis was found in only one patient. Total thyroidectomy was performed in 18, subtotal thyroidectomy in 9 and lobectomy with isthmus resection in 9 patients. Thyroiditis accompanying the carcinonoma was diagnosed in 3 patients. Regional lymph node recurrence occurred in 8 cases. One patient was lost only, due to local recurrence. All of the patients were given thyroid hormone replacement. 20 patients became pregnant after the treatment, and 25 infants were born.