Prognostic impact of thyroid lymphocytic infiltration in patients with medullary thyroid carcinoma.
ABSTRACT A retrospective search for lymphocytic infiltration of the thyroid was performed on archival paraffin specimens from 95 cases of thyroid medullary carcinoma observed at a single institution during a 30-year period. A mild lymphocytic infiltration of the nonneoplastic thyroid tissue, mainly concentrated at the edge of the tumor mass, was observed in 33 cases, while in a further 24 cases a moderate to marked lymphocytic infiltration, resembling that seen in chronic lymphocytic thyroiditis, was homogeneously distributed all over the gland, with no apparent relationship to the site of the primary tumor. Virtually no lymphocytic infiltration was detected inside of any of the tumors. The presence of chronic lymphocytic thyroiditis seemed to be a characteristic of the host rather than a tumor-induced event. Statistical univariate analysis of relapse-free survival and overall survival showed that lack of chronic lymphocytic thyroiditis marked those patients with an increased risk of disease recurrence and death. However, the observed risk for survival was statistically nonsignificant, whereas that for disease recurrence was significant and remained in a multivariate model of statistical analysis.
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ABSTRACT: BACKGROUND: Reliable predictive biomarkers are required to address the challenge of disease recurrence after thyroid cancer surgery. For this study, the authors assessed the association of cellular-based and serum-based immunologic mediators with thyroid cancer recurrence. METHODS: Leukocyte subset counts and immune regulatory cytokine levels were determined in peripheral blood samples using multiparameter flow cytometry and 51-panel, multiplex enzyme-linked immunosorbent assays, respectively. The functional activity of circulating B-lymphocytes, T-lymphocytes, and natural killer lymphocytes was assessed ex vivo. Differences in mean biomarker levels between defined patient groups and correlations between biomarkers and cancer recurrence were assessed using t tests or Wilcoxon tests and by univariate and multivariate analyses with Cox models. Optimal cutoff values of significantly correlated biomarkers that best predicted disease recurrence after surgery were established by receiver operating characteristics and were validated by using an optimal cutpoint determination algorithm. RESULTS: In total, 35 patients were enrolled (median age, 49.4 year), including 24 women and 15 patients with recurrent disease; and there were 21 individuals in the control group. Patients without recurrence had higher levels of soluble FAS (tumor necrosis receptor superfamily, member 6) ligand (sFASL), transforming growth factor-β, regulatory T cells, and programmed death 1/ programmed death ligand 1-expressing leukocytes. sFASL (hazard ratio, 0.60; 95% confidence interval, 0.38-0.95; P = .031) and interferon-α (hazard ratio, 1.55; 95% confidence interval, 1.03-2.34; P = .038) were associated significantly with disease recurrence. There was a significant difference in progression-free survival between patient groups stratified by an sFASL optimal cutpoint of 15 pg/mL (log-rank P = .0009). CONCLUSIONS: sFASL and IFN-α levels were correlated significantly with thyroid cancer recurrence and may be useful for risk-adapted surveillance strategies in patients with thyroid cancer. Cancer 2013. © 2013 American Cancer Society.Cancer 01/2013; · 5.20 Impact Factor
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ABSTRACT: Injection of AKR/N mice with fibroblasts co-expressing MHC class II and TPO in the absence of adjuvant induces IgG-class TPO antibodies that resemble spontaneously arising human thyroid autoantibodies. We have used this model to examine the effect of iodide on TPO antibody induction as well as to analyse the interaction between T and B cells. Despite its importance as a major environmental factor in thyroid autoimmunity, variable iodide intake had no detectable effects on TPO antibody levels, lymphocytic infiltration of the thyroid or thyroid hormone levels. In terms of T cell responsiveness, splenocytes from TPO fibroblast-injected mice, but not from control mice, proliferated in response to TPO. Intriguingly, B cell-depleted splenocytes (mainly T cells without reduction of macrophages) proliferated in response to TPO only when co-cultured with irradiated autologous splenocytes from TPO fibroblast-injected mice but not from control mice. These data suggest that TPO-specific B cells are involved in antigen presentation to sensitized T cells and are supported by the ability of spleen cells from TPO cell-injected (but not control) mice to secrete TPO antibodies spontaneously in culture. In conclusion, we provide the first evidence for the presence of thyroid autoantigen-specific B cells and their ability to present their autoantigen to sensitized T cells in mice induced to develop TPO antibodies resembling autoantibodies in humans.Clinical & Experimental Immunology 01/2000; 119(1):38-46. · 3.28 Impact Factor
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ABSTRACT: The effect of chronic lymphocytic thyroiditis (CLT) on the behavior of papillary thyroid cancer (PTC) remains unclear. In recent studies the presence of CLT in patients with PTC was reported to be associated with a lower recurrence rate and an improved survival rate. Furthermore, patients with PTC and tumor infiltrating lymphocytes (TILs) have been reported to have lower recurrence rates and a lower frequency of distant metastases. Because of these and other observations, a tumor immune response in PTC has been suggested. The aim of our study was to determine: (1) the relative frequency of CLT in PTC; (2) the prognostic significance of CLT in patients with PTC; and (3) if TIL occurs independently or in association with CLT. A 10-year retrospective study of patients who underwent initial thyroidectomy for PTC from 1986 to 1996 was completed. The extent of thyroid lymphocytic infiltration was determined within the tumor, surrounding the tumor, and in the distant parenchyma by two independent observers blinded to the clinical data. Dense focal/diffuse lymphoid aggregates throughout the thyroid gland were diagnostic of CLT and when present within or surrounding the tumor were designated TILs. A total of 136 patients with PTC (typical and follicular variant of PTC histologic subtypes) were identified with a mean follow-up of 4.4 years and a 8% mortality rate at 10 years. Thirty percent of the patients with PTC had coexisting CLT, and 65% of these patients with CLT had positive anti-thyroglobulin antibodies. Patients with coexisting CLT and PTC were younger (p < 0.05), more likely to be female (p < 0.05), and more likely to have multicentric tumors (p < 0.001) compared to patients without CLT. Only 5% of patients had TILs without CLT, but 82.5% of patients with CLT had TILs identified (p < 0.0001). By univariate analysis CLT, age, gender, stage of PTC, tumor multicentricity, and tumor size were significant prognostic factors. Only age and TNM stage of PTC remained independent prognostic factors by multivariate analysis. We found a similar frequency (30%) of coexisting CLT and PTC as reported by others; but, more importantly, the presence of TILs primarily occurred in association with CLT. The presence of CLT in patients with PTC correlated with an improved prognosis. It was not an independent prognostic factor, however, and was not associated with a lower recurrence rate or a lower frequency of distant metastasis.World Journal of Surgery 05/2001; 25(5):632-7. · 2.35 Impact Factor