Clinical Significance of P53 Protein Expression in Papillary Thyroid Carcinoma

BACKGROUND: Although mutations in the p53 suppressor gene in thyroid carcinoma have usually been detected in anaplastic carcinoma, P53 protein expression has been detected immunohistochemically in papillary thyroid carcinoma (PTC). In the present study, we examined the immunohistochemical expression of P53 protein in PTC to investigate the relations between its expression and the clinicopathologic features. METHODS: The study was performed on 68 patients in whom thyroidectomy with lymph node dissection had been performed to treat PTC at Teikyo University Hospital. Expression of P53 protein was evaluated immunohistochemically in sections of paraffin-embedded tissue in 68 primary tumors and 196 lymph node metastases. RESULTS: Overexpression of P53 protein in the primary tumor was observed in 29 cases (43%). Statistical analysis revealed significant correlation between P53 protein expression in the primary tumor and large tumor size (unpaired t-test: p < 0.01), the presence of lymph node metastasis (unpaired t-test: p < 0.05), and the mean number of lymph node metastases (unpaired t-test: p < 0.05). Although 29 (43%) of the primary tumors overexpressed P53 protein, 143 (73%) of the metastatic lymph nodes overexpressed P53 protein irrespective of whether there was P53 overexpression by the primary tumor. CONCLUSIONS: The results of this study suggest that immunohistochemistry for P53 in the primary tumor could be useful in the clinical evaluation of patients with PTC. Moreover, P53 protein overexpression in lymph node metastasis may be useful as a treatment guide or target for lymph node recurrences.     

Detection of sentinel lymph nodes in patients with papillary thyroid cancer

OBJECTIVES: To determine the feasibility of sentinel lymph node biopsy as a means of evaluating the cervical lymph nodes of patients with papillary thyroid cancer. METHODS: Isosulfan blue dye was injected around the tumour of 68 patients with papillary thyroid cancer; sentinel lymph node biopsy was performed in addition to subtotal thyroidectomy and central and modified lateral neck lymph node dissections. Surgical specimens were examined by routine processing to determine whether metastasis was present. RESULTS: Sentinel lymph nodes were identified in 63 (92.6%) of the 68 patients. There was concordance between the sentinel lymph node status and the final regional lymph node status in 58 (92.1%) of the 63 patients. There were five false-negative cases. Sentinel lymph node biopsy had a sensitivity of 87.5% (35/40), specificity of 100% (23/23), positive predictive value of 100% (35/35), negative predictive value of 82.1% (23/28), and accuracy of 92.1% (58/63). CONCLUSIONS: Sentinel lymph node biopsy may allow discrimination between patients with true lymph-node-negative papillary thyroid carcinoma and those with non-palpable metastatic lymph nodes. It may also be helpful in diagnosing metastases and avoiding unnecessary lymph node dissection in thyroid cancer.     

Calcitonin gene-related peptide as a tumor marker for medullary thyroid carcinoma.

We have established a radioimmunoassay method for calcitonin gene-related peptide (CGRP) to monitor changes in plasma CGRP levels in patients with medullary thyroid carcinoma (MTC). Preoperative plasma CGRP levels (normal level less than 12.7 pg/ml) were as high as 128 pg/ml to 2,010 pg/ml in all five patients with MTC. Ten of 17 postoperative patients with MTC were positive for CGRP. A provocation test was performed in 12 patients with MTC. Plasma CGRP changes roughly paralleled serum calcitonin levels. In particular, in three patients with poorly-differentiated MTC which progressed aggressively, plasma CGRP levels were increased to 1.4 to 2.0 times levels before the test, i.e., lower than the 2.8- to 23.3-fold increase in nine patients with the well-differentiated MTC. These results suggest that CGRP may be a humoral marker of medullary carcinoma and be related to degree of malignancy.     

Impaired response of granulocyte-committed progenitor cells to stem cell factor and granulocyte colony-stimulating factor in human cyclic neutropenia

 Although cyclic neutropenia (CN) has been the subject of extensive studies due to its striking clinical picture, the abnormality of hematopoietic progenitor cells in patients with CN has been poorly defined. We studied the sensitivity of progenitor cells of a CN patient to colony-stimulating factors (CSF) including G-CSF, interleukin-3 (IL-3), and stem cell factor (SCF). Peripheral blood progenitor cells of the patient required a significantly higher dose of G-CSF to give rise to colonies than those of normal controls. While the presence of SCF enhanced the number of G-CSF-induced colonies regardless of the concentration of G-CSF in normal controls, this synergistic effect of SCF was limited to the high concentration of G-CSF in the patient, indicating that the abnormality in hematopoiesis in CN involved more immature progenitor cells responsive to SCF. Received: July 30, 1998 / Accepted: November 12, 1998     

Expansion and activation of minor histocompatibility antigen HY-specific T cells associated with graft-versus-leukemia response

The immune system of females is capable of recognizing and reacting against the male-specific minor histocompatibility antigen (mHA), HY. Thus, cytotoxic T-lymphocytes (CTLs) recognizing this antigen may be useful in eradicating leukemic cells of a male patient if they can be generated in vivo or in vitro from a human leukocyte antigen (HLA)-identical female donor. The HLA-A*0201-restricted HY antigen, FIDSYICQV, is a male-specific mHA. Using HLA-A2/HY peptide tetrameric complexes, we reveal a close association between the emergence of HY peptide-specific CD8(+) T cells in peripheral blood and molecular remission of relapsed BCR/ABL(+) chronic myelogenous leukemia in lymphoid blast crisis in a patient who underwent female-to-male transplantation. Assessment of intracellular cytokine levels identified T cells that produce interferon-gamma in response to the HY peptide during the presence of HY tetramer-positive T cells. These results indicate that transplant with allogeneic HY-specific CTLs has therapeutic potential for relapsed leukemia, and that expansion of such T cells may be involved in the development of a graft-versus-leukemia response against lymphoblastic leukemia cells.     

Serum concentration of L‐kynurenine predicts the clinical outcome of patients with diffuse large B‐cell lymphoma treated with R‐CHOP

Purpose: Introduction of rituximab has largely improved the prognosis of patients with diffuse large B‐cell lymphoma(DLBCL). Such change in therapeutic outcome necessitates the identification of additional prognostic factors to conventional indexes that have been validated for CHOP without rituximab. Indoleamine 2,3‐dioxygenase (IDO) exerts intense immunomodulatory effects because of enzymatic activities that catalyze the breakdown of the essential amino acid L‐tryptophan. The activity of IDO can be estimated by measuring the serum concentration of L ‐kynurenine. Here, we investigated the role of L ‐kynurenine as a prognostic marker in R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) therapy. Experimental design: Data from 73 consecutive patients treated with eight cycles of R‐CHOP or R‐THP (tetrahydropyranyl adriamycin)‐COP between December 2002 and March 2007 were analyzed. L ‐kynurenine concentrations in serum samples obtained at admission were measured by high‐performance liquid chromatography. Results: The median serum L ‐kynurenine level was 1.575 μm (range 0.537–9.588). The complete response (CR) rates of patients with L ‐kynurenine <1.5 and ≥1.5 μm were 83% and 61%, respectively (P < 0.05). The three‐yr overall survival (OS) rates for patients with L ‐kynurenine <1.5 and ≥1.5 μm were 89% and 58%, respectively (P < 0.005). In addition, higher age, poor performance status, elevated serum lactate dehydrogenase, and unfavorable as well as revised International Prognosis Index were significantly worse factors for CR rate and OS. Multivariate analyses revealed only L ‐kynurenine as an independent prognostic factor for OS. Conclusions: Serum L ‐kynurenine might be a novel prognostic factor to determine the treatment outcome of DLBCL with the R‐CHOP regimen.     

Orbital T-cell lymphoma in a multiple myeloma patient

PURPOSE: To report an 82-year-old woman with multiple myeloma who developed an orbital T-cell lymphoma concomitantly. METHODS: The patient presented with left upper eyelid swelling. Magnetic resonance imaging demonstrated an orbital mass compressing the eyeball. The mass was excised for diagnostic purposes and orbital decompression. RESULTS: Histopathologic and immunohistochemical evaluation identified the mass as a T-cell lymphoma. The disease progressed rapidly despite chemotherapy. CONCLUSIONS: Orbital T-cell lymphoma is rare and we are unaware of previous reports of orbital T-cell lymphoma in patients with multiple myeloma.     

Bone mineral measurement in evaluation of osteoporosis treatment

BMD measurement is the most common practical method to evaluate the efficacy of the treatment. As the signal/noise ratio of lumber BMD is better than the other part of BMD measurement, the best site for the evaluation of therapy is lumber spine. If evaluation at lumber spine is difficult, hip BMD, followed by peripheral BMD may be selected. Special care must be taken if peripheral BMD is measured, because of low signal/noise ratio. The interval between BMD measurements is usually 6 months, and it should be longer than this period, if peripheral BMD is utilized.