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Jennifer L Hunt

Publications and source records attributed to Jennifer L Hunt.

At least 37 records · Page 2Linked to original sources
PubMed2005

Unusual adrenal cortical tumor of unknown biologic potential: a nodule in a nodule in a nodule.

Adrenocortical tumors are uncommon neoplasms in childhood. Most pediatric adrenal tumors are virilizing and carcinomas are more common than adenomas. Recent molecular data suggest an adenoma-to-carcinoma progression sequence in adrenal cortical neoplasms. We report a case of a 5-year-old boy who presented with virilizing symptoms secondary to an adrenal tumor that was resected laparoscopically. The bulk of the tumor was a large, yellow mass with typical features of an adrenal cortical adenoma. In the center was a well-circumscribed tan-brown nodule that was distinct from the adenoma and had oncocytic features. A third minute focus (3.0 mm) was noted that was not circumscribed or encapsulated, but showed marked pleomorphism and abundant mitoses, including atypical forms and increased Ki67 compared with the outer 2 nodules. Molecular analysis to assess the clonality and mutation rates of the 3 distinct areas showed only 2 genetic loci with allelic imbalances.

Adrenal Cortex Neoplasms↗
PubMed2005

Cultured podocytes establish a size-selective barrier regulated by specific signaling pathways and demonstrate synchronized barrier assembly in a calcium switch model of junction formation.

Podocytes form unique cell-cell junctions (slit diaphragms) that are central to glomerular selectivity, although regulation and mechanisms of slit diaphragm assembly are poorly understood. With the use of cultured podocytes, a paracellular permeability flux assay was established to characterize properties of the size-selective barrier. Paracellular flux of differentiated podocytes was measured using anionic fluorescent dextrans of 3, 10, 40, and 70 kD. Podocytes form a highly selective barrier with a 160-fold difference in flux from the 3-kD dextran (11 pmol/min) to the 70-kD dextran (0.06 pmol/min). Barrier development was dependent on podocyte differentiation and not affected by dextran charge. Puromycin, a known podocyte toxin, increased flux 250% in a dose-dependent manner without affecting cell viability. Screening with modulators of specific signaling pathways identified reversible increases in flux with Src tyrosine and Rho kinase inhibition. The calcium switch model of epithelial junction assembly was modified to determine whether podocytes regulate barrier assembly. When cultured in low calcium for 90 min, flux increased by 300% and consistently returned to baseline 24 to 48 h after switching to normal calcium. Similar to classical epithelial junctions, barrier recovery occurred in the presence of cyclohexamide, an inhibitor of protein synthesis. During the calcium switch, there were reversible changes in localization and detergent solubility of the slit diaphragm protein ZO-1 and alpha-actinin-4, whereas nephrin and podocin solubility were unchanged. Taken together, these findings demonstrate that cultured podocytes develop a selective size barrier that is regulated by specific signaling pathways, and similar to classical epithelial junctions, podocytes demonstrate synchronized assembly of the barrier.

Animals↗
PubMed2005

Molecular staging of cervical lymph nodes in squamous cell carcinoma of the head and neck.

Clinical staging of cervical lymph nodes from patients with squamous cell carcinoma of the head and neck (SCCHN) has only 50% accuracy compared with definitive pathologic assessment. Consequently, both clinically positive and clinically negative patients frequently undergo neck dissections that may not be necessary. To address this potential overtreatment, sentinel lymph node (SLN) biopsy is currently being evaluated to provide better staging of the neck. However, to fully realize the potential improvement in patient care afforded by the SLN procedure, a rapid and accurate SLN analysis is necessary. We used quantitative reverse transcription-PCR (QRT-PCR) to screen 40 potential markers for their ability to detect SCCHN metastases to cervical lymph nodes. Seven markers were identified with good characteristics for identifying metastatic disease, and these were validated using a set of 26 primary tumors, 19 histologically positive lymph nodes, and 21 benign nodes from patients without cancer. Four markers discriminated between positive and benign nodes with accuracy >97% but only one marker, pemphigus vulgaris antigen (PVA), discriminated with 100% accuracy in both the observed data and a statistical bootstrap analysis. A rapid QRT-PCR assay for PVA was then developed and incorporated into a prototype instrument capable of performing fully automated RNA isolation and QRT-PCR. The automated analysis with PVA provided perfect discrimination between histologically positive and benign lymph nodes and correctly identified two lymph nodes with micrometastatic tumor deposits. These assays were completed (from tissue to result) in approximately 30 minutes, thus demonstrating the feasibility of intraoperative staging of SCCHN SLNs by QRT-PCR.

Adult↗
PubMed2005

Molecular assessment of allelic loss in Warthin tumors.

Warthin's tumors are benign lesions of the head and neck that have a characteristic morphologic appearance. The etiology of Warthin's tumors is controversial and whether they are true neoplasms or developmental malformations continues to be debated. In this study, we examined 12 Warthin tumors with a molecular and immunohistochemical approach. Immunostains for p53 and p16ink were performed. The epithelial and lymphoid components of each lesion were microdissected and PCR was performed for 13 microsatellite markers at or near common tumor suppressor genes. The results were analyzed semiquantitatively using capillary electrophoresis. Frequency of allelic loss was calculated. The epithelial component of all tumors was negative for p53 and p16ink. By molecular genotyping there was only one case that had one locus with allelic imbalance, while the remainder had no evidence of clonal allelic loss. The immunohistochemical and molecular results in this study lend support to the hypothesis that Warthin tumors are non-neoplastic, as there was no evidence of aberrant staining for tumor suppressor gene protein products and no evidence of consistent clonal allelic losses.

Aged↗
PubMed2005

Controversial ectopic thyroid: a case report of thyroid tissue in the axilla and benign total thyroidectomy.

A 43-year-old woman presented with a mass in her left axilla, which was surgically excised. Histologically, the tissue was a reactive lymph node with adjacent thyroid follicular tissue. The differential diagnosis included benign ectopic thyroid versus metastatic well-differentiated follicular-derived thyroid carcinoma. Because of the possibility of carcinoma, the patient underwent a diagnostic total thyroidectomy. The thyroid was grossly normal with no histologic evidence of malignancy. Post-operatively, the patient underwent a whole body 131I scan. Aside from an expected residual uptake in the thyroid bed region, there was no extrathyroidal uptake to suggest additional ectopic thyroid tissue or metastatic disease. At the time of this scan, her thyrotropin (TSH) was 92.8 microU/mL, thyroglobulin was less than 0.3 ng/mL, and thyroglobulin antibody was less than 3 IU/mL. Abnormalities in the embryologic development and migration of the thyroid gland can result in ectopic thyroid tissue. The most frequent locations are along the midline from the base of the tongue to the mediastinum. Only rare case reports exist of ectopic thyroid in other locations, including the chest (heart, trachea), abdomen (liver, gallbladder, pancreas), and pelvis (vagina). This case represents the first description of thyroid tissue in the axilla with a histologically benign thyroid gland.

Adult↗
PubMed2005

Immunophenotypic comparison of salivary gland oncocytoma and metastatic renal cell carcinoma.

OBJECTIVES/HYPOTHESIS: The differential diagnosis of oncocytic neoplasms of salivary glands includes both primary and metastatic tumors, one of which is renal cell carcinoma. This study compared immunohistochemical staining characteristics of oncocytomas arising from salivary gland to metastatic renal cell carcinoma using a panel of markers. STUDY DESIGN: Immunohistochemistry for cytokeratin 7 (CK7), cytokeratin 20 (CK20), epithelial membrane antigen (EMA), vimentin, CD10, and renal cell carcinoma marker (RCC) was performed on 10 oncocytomas and compared with ten metastatic renal cell carcinomas. RESULTS: There were overlapping histologic findings in the oncocytomas and metastatic renal cell carcinomas, with oncocytomas displaying clear cell changes in 2 of 10 cases. CK7 was positive in 9 of 10 oncocytomas and CK20 in 8 of 10 (7/10 stained for both), and vimentin was only weakly positive in 4 of 10 oncocytomas. All oncocytomas were EMA positive, with membranous staining, and all were negative for CD10 and RCC. Metastatic renal cell carcinoma was strongly positive for vimentin, EMA, and CD10 in most cases. RCC and CK7 were variably positive in metastatic renal cell carcinomas (4/10), and only 1 of 10 showed weak staining with CK20. CONCLUSIONS: Salivary gland oncocytomas and metastatic renal cell carcinomas share some similar histologic and immunohistochemical characteristics. CD10 and CK20 were the most useful markers to distinguish metastatic renal cell carcinoma from oncocytomas in the salivary gland, whereas RCC, EMA, CK7, and vimentin are not as useful.

Adenoma, Oxyphilic↗
PubMed2005

Potential diagnostic use of p16INK4A, a new marker that correlates with dysplasia in oral squamoproliferative lesions.

Protein products of tumor suppressor genes are often involved in regulating the cell cycle, and aberrant expression can correlate with underlying genetic mutations. Mutations in the p16 gene have been detected at relatively high rates in squamous cell carcinomas of the oral cavity. However, immunohistochemical staining for the protein product has not been examined as a diagnostic tool for identifying dysplastic lesions in the oral cavity. Sixty cases of biopsies of reactive, inflammatory, and dysplastic lesions of all grades were stained with an antibody to p16INK4A and analyzed for which layer of the epithelium had positive cells. Staining was seen only in the basal or lower third in keratoses and mild dysplasias and was seen in the mid and upper thirds in moderate to severe dysplasia. The staining across larger fragments of biopsied epithelium highlighted skip lesions, with strong staining restricted to dysplastic regions. Inflammatory lesions, including chronic ulcers, showed absent or minimal basal layer staining with p16INK4A. In this preliminary study, p16INK4A shows promise as to a potential marker to aid in recognizing the presence of dysplasia in squamous mucosa of the head and neck, particularly in subtle lesions, and in an inflammatory or ulcerated background.

Biomarkers, Tumor↗
PubMed2005

Recurrent sarcoidosis in lung transplant allografts: granulomas are of recipient origin.

INTRODUCTION: Sarcoidosis accounts for only 2.8% of lung transplants in the United States. It is, however, the most commonly reported disease to recur after lung transplantation. In most cases, recurrence is diagnosed as an incidental finding in transbronchial lung allograft biopsy (TBLAB) and is unrelated to clinical or radiologic abnormalities. The origin of the histiocytes composing the noncaseating granulomas in the allograft lung in patients with recurrent sarcoidosis (RS) was analyzed using DNA identity testing in 4 cases. MATERIAL AND METHODS: Native lung resections and corresponding transbronchial biopsies from patients who underwent lung transplantation for sarcoidosis between 1990 and 2004 and who developed RS were gathered from the paraffin block archives of University of Pittsburgh Medical Center. Clinical parameters including age, sex, grade of rejection, number of episodes of RS, and follow-up were recorded. Native lungs and corresponding TBLAB showing granulomas consistent with RS were microdissected in cases where adequate material was available. DNA was extracted, and an ABI AmpflSTR commercial kit was used to simultaneously amplify 15 short tandem repeat (STR) loci as well as 1 marker for the XY chromosomes. The informative STR loci in native lung (pure recipient), nongranulomatous donor lung, and granulomas in donor lung were analyzed in 4 patients. The relative proportion of donor and recipient cells in the chimera was quantified using the fluorescence intensity of each peak on an electropherogram. FISH analysis using probes targeted to X and Y chromosomes was performed in a case of sex-mismatched lung transplantation. RESULTS: Eight patients with RS were identified. Two had bilateral lung transplantation, and the remaining 6 had single-lung transplantation. The age at transplantation ranged between 39 and 53. Five were females and 3 were men. Recurrent disease was diagnosed in 1 to 11 biopsies per patient and occurred first in the first 6 months following transplantation in 2 cases (25%), between 6 months and 1 year in 2 other cases (25%), and between 1 and 2 years in 4 cases (50%). In 4 patients, sufficient material allowed for DNA analysis. Amplification failed in 1 of the 4 cases, while the other 3 were successful. Patient 1 showed no ACR and granulomatous inflammation of RS in TBLAB. Donor (D) to recipient (R) profile changed from "normal" donor lung (37% D, 63% R) to 15% D and 85% R DNA in the granuloma. In patient 2, the TBLAB showed minimal ACR and granulomatous inflammation. D to R profile changed from 75% D and 25% R in the "normal" D lung to 54% D and 46% R in the granuloma. Patient 3 showed no ACR and RS in TBLAB. D to R profile changed from 85% D and 15% R in the "normal" D lung to 71% D and 29% R in the granuloma. FISH analysis showed a predominance of male cells of recipient origin. CONCLUSIONS: DNA analysis of 3 cases of RS suggests that the presence of recurrent granulomas in the graft is associated with an increase in the percentage of recipient DNA in the epithelioid cell clusters, as confirmed by the FISH analysis of 1 case.

Adult↗
PubMed2005

Human leukocyte antigen (HLA) class I defects in head and neck cancer: molecular mechanisms and clinical significance.

The potential role of immunological events in the pathogenesis and clinical course of head and neck squamous cell carcinoma (SCCHN) has stimulated interest in the characterization of HLA class I antigen expression in SCCHN lesions, because these molecules play an important role in the interaction of malignant cells with the host's immune system. Therefore in this paper, following a description of the methodology used to analyze HLA class I antigen expression in normal tissues and in malignant lesions, we have reviewed data about the frequency of HLA class I antigen defects in about 500 primary and in about 25 metastatic SCCHN lesions. The mean frequency of total HLA class I antigen loss in primary and metastatic lesions is approx 15% and 40%, respectively. The mean frequency of selective HLA class I antigen loss in primary lesions is approx 37%. This type of abnormality has not been investigated in metastatic lesions so far. The molecular mechanisms underlying HLA class I antigen defects in SCCHN cells have been investigated to a limited extent. The available information suggests that structural defects in beta2m genes are rare. In contrast, functional abnormalities of the antigen processing machinery (APM) components are frequent in SCCHN cells. The latter abnormalities are likely to account for the unusual finding that most of SCCHN cell lines are resistant in vitro to HLA class I antigen restricted, tumor antigen (TA)-specific CTL recognition under basal conditions in spite of the expression of TA and HLA class I antigens. CTL recognition of SCCHN cells is restored by incubation with IFN-gamma. These in vitro findings provide a mechanism for the association between APM component defects in SCCHN lesions and clinical course of the disease and imply that T cell-based immunotherapy of SCCHN may benefit from the intralesional administration of IFN-gamma.

Animals↗
PubMed2005

Unusual thyroid tumors: a review of pathologic and molecular diagnosis.

The most common thyroid neoplasms are either follicular derived (papillary, follicular and Hürthle cell lesions) or C-cell derived (medullary carcinoma). The diagnosis of these tumors can usually be made at the histologic level, with immunohistochemical stains necessary in some circumstances. Specific molecular mutations have been described that can be diagnostically useful or explain, in part, their pathogenesis, including the well-known Ret/PTC and PPARgamma-PAX8 translocations, point mutations in the Ret, Ras and BRAF genes, and loss of heterozygosity of multiple different tumor suppressor genes. Some unusual tumors of the thyroid gland are more difficult to diagnose. In examining these lesions, the pathologist may use the hematoxylin and eosin-stained morphology, coupled with an analysis of the immunohistochemical staining profiles and possibly analysis of the underlying molecular mutational patterns. These less common thyroid tumors include tall cell and cribriform-morular variants of papillary carcinoma, hyalinizing trabecular tumor, mucoepidermoid and sclerosing mucoepidermoid carcinoma with eosinophilia, poorly differentiated (insular) carcinoma, and undifferentiated (anaplastic) carcinoma. The diagnostic features of these rare tumors, including the histology, immunohistochemical expression profiles and the known molecular mutational profiles of each, are reviewed.

Adenocarcinoma↗
PubMed2005

Nasal chondromesenchymal hamartoma in older children and adults: series and immunohistochemical analysis.

CONTEXT: Nasal chondromesenchymal hamartoma is a benign mass lesion of the nasal cavity predominantly described in young infants. These unusual lesions are composed of a proliferation of mesenchymal and cartilaginous elements. Their pathogenesis is unknown, but they may be derived from embryologic rests. To our knowledge, only 1 case in an older child has been reported, and no cases have been reported in adults. OBJECTIVE: To report 4 cases of nasal chondromesenchymal hamartoma occurring in older children and adults, including immunohistochemical analysis of these unusual lesions. DESIGN: Cases identified from our archives were examined to confirm the diagnosis of nasal chondromesenchymal hamartoma. Immunohistochemical analysis was performed using a panel of antibodies (epithelial membrane antigen, smooth muscle actin, all muscle actin, cytokeratin, S100, and KP1) to evaluate for epithelial, smooth muscle, neural, chondroid, and histiocytic differentiation. RESULTS: Four cases of nasal chondromesenchymal hamartoma in patients of 11, 69, 17, and 25 years of age demonstrated histologic evidence of mesenchymal and cartilaginous elements underlying a chronically inflamed respiratory mucosa. Bony and adipose elements and rare glandular elements were interspersed. Cartilaginous elements stained strongly with S100, whereas mesenchymal regions showed variable and weaker staining. Smooth muscle differentiation was seen primarily in the mesenchymal areas. Epithelial membrane antigen was focally positive in all cases. CONCLUSIONS: Nasal chondromesenchymal hamartomas can rarely occur in the older child and adult. Mesenchymal areas show both myofibroblastic and cartilaginous differentiation. We speculate that inflammation or a recapitulation of developmental signals may be components in the pathogenesis of these lesions.

Adolescent↗
PubMed2005

Allelic loss in parathyroid neoplasia can help characterize malignancy.

Parathyroid carcinoma can be difficult to diagnose, and the final pathologic diagnosis relies on clinicopathologic correlation. Clinical features of malignancy include high preoperative calcium levels and an intraoperative impression that the gland is adherent to local structures. Histologic features of malignancy include increased mitoses, vascular invasion, and broad bands of fibrosis. This study used molecular genotyping to assess parathyroid neoplasia for loss of heterozygosity across a panel of known tumor suppressor genes that have been previously identified as being important in the pathogenesis of parathyroid diseases. Parathyroid adenomas, hyperplasia, and carcinomas were included in the study, and a fractional allelic loss was calculated for each lesion. Losses of 1q25, 7q13.3, 10q23, 13q14.3, and 11p15.5 were particularly prevalent. In addition, almost all adenomas and carcinomas had loss of the markers for 1p. The benign parathyroid diseases (adenomas and hyperplasia) had low mean fractional allelic loss (11% and 15%, respectively). The parathyroid carcinomas, in contrast, showed high mean fractional allelic loss (63%). This difference in the mutational profile suggests that this type of assay may be useful as an adjunctive diagnostic test in cases of parathyroid neoplasia.

Adenoma↗
PubMed2004

Correlation of protease-activated receptor-1 with differentiation markers in squamous cell carcinoma of the head and neck and its implication in lymph node metastasis.

PURPOSE: Protease-activated receptor-1 (PAR-1) is a G-protein-coupled receptor that contributes to multiple signal transduction pathways. Although the functions of PAR-1 in many normal cells, such as platelets and astrocytes, have been well studied, its roles in cancer progression and metastasis have not been fully elucidated, and studies to date appear contradictory. EXPERIMENTAL DESIGN: To clarify the function of PAR-1 in metastasis of squamous cell carcinoma of the head and neck (SCCHN), we examined PAR-1 expression in clinical specimens by immunohistochemistry and in SCCHN cell lines by immunoblotting. Furthermore, par-1 cDNA-transfected SCCHN cell lines were also used to verify PAR-1-mediated pathway. RESULTS: The metastatic tumors showed a lower percentage of PAR-1-positive cells (46%) and lower levels of PAR-1 expression (median weight index = 10) than node negative primary tumors (80% and median weight index = 60, respectively). In addition, expression level of PAR-1 positively correlated with levels of keratinocyte differentiation markers keratin-1, -10, and -11. Additional studies using sense and antisense par-1 cDNA-transfected SCCHN cell lines illustrated that the presence of PAR-1 was required for the expression of involucrin, a keratinocyte differentiation marker. PAR-1 expression also contributes to activation of the mitogen-activated protein kinase (MAPK) pathway. Blocking MAPK activation by a mitogen-activated protein/extracellular signal-regulated kinase inhibitor, not by a phosphatidylinositol 3'-kinase inhibitor, reduced level of involucrin, suggesting that regulation of involucrin by PAR-1 is partially through the MAPK signaling pathway. CONCLUSIONS: Our study suggests that PAR-1 signaling induces differentiation markers in SCCHN cells, and its expression is conversely correlated with cervical lymph node metastasis.

Adult↗
PubMed2004

Expression pattern of chemokine receptor 6 (CCR6) and CCR7 in squamous cell carcinoma of the head and neck identifies a novel metastatic phenotype.

Squamous cell carcinoma of the head and neck (SCCHN) metastasizes predictably to cervical lymph nodes, with low rates of distant metastases. Tumor cells can express various receptors that facilitate such metastatic spread to lymph nodes and other nonlymphoid organs. Chemokine receptors (CCR), normally expressed on lymphocytes, control immune and inflammatory cell migration, providing a link between innate and adaptive immunity. Chemokine receptor expression was evaluated in SCCHN, using paired primary and metastatic tumors cell lines, and paired primary and metastatic biopsies from the same patients. Quantitative reverse transcription-PCR showed a consistent pattern of CCR6 down-regulation and up-regulation of CCR7 in metastatic cells and tissues. Chemotaxis assays, ligand-induced receptor down-regulation, and specific antibody blocking experiments supported the quantitative reverse transcription-PCR results, indicating that these surface receptors were functional on metastatic tumor cells. Cells derived from a highly metastatic mouse model of SCCHN were used to confirm CCR7 up-regulation in tumor cells with higher metastatic potential. CCR6 down-regulation is consistent with its decreased expression in cells emigrating from peripheral mucosal sites, whereas CCR7, important for homing of immune cells to secondary lymphoid organs, was significantly up-regulated. Thus, CCR6, CCR7, and their ligands, normally important in controlling immune cell trafficking in response to inflammatory stimuli, may have an important role in determining the metastasis of SCCHN cells in vivo.

Carcinoma, Squamous Cell↗
PubMed2004

Prostatic adenocarcinoma metastatic to the head and neck and the workup of an unknown epithelioid neoplasm.

BACKGROUND: Epithelioid tumors in the head and neck are common and include both primary and metastatic lesions. For metastatic lesions, clinical factors, tumor location, and ancillary immunohistochemical studies must be taken into consideration to help the clinician and the pathologist determine the site of origin. One unusual, but important, primary tumor that can metastasize to the head and neck is carcinoma of the prostate (CAP). METHODS: The files of the University of Pennsylvania Department of Pathology were searched for cases of metastatic CAP. All slides were examined, and clinical information was obtained from the referring physician's patient charts. RESULTS: We describe 14 cases of metastatic CAP to the head and neck. Six patients had no history of CAP at the time of biopsy of the head and neck metastasis, and only eight patients had other widespread metastatic disease. Histologically, most of the tumors had epithelioid cells with prominent nucleoli and cribriform, solid, or infiltrating single cell growth patterns. PSA and PSAP immunohistochemical stains were positive in all cases. Seven of 12 patients with known follow-up are alive after radiation or hormonal therapy. CONCLUSIONS: These results demonstrate a fair prognosis with possible prolonged survival with metastatic CAP to the head and neck after appropriate diagnosis and subsequent hormone and radiation therapy. Given this survival advantage with treatment, it is critical to consider the diagnosis of metastatic CAP when evaluating a metastatic malignant epithelioid tumor in the head and neck of an elderly man.

Adenocarcinoma↗
PubMed2004

p63 expression in sclerosing mucoepidermoid carcinomas with eosinophilia arising in the thyroid.

Primary sclerosing mucoepidermoid carcinomas with eosinophilia (SMECE) of the thyroid gland are rare tumors that can present diagnostic difficulties to the pathologist due to the unusual histologic features. Furthermore, the etiology of these tumors has been debated in the literature, with some authors believing that the tumors arise from remnants of the ultimobranchial body (UBB, solid cell nests) and others proposing that they arise from follicular epithelial cells. Because SMECE often occur in glands with chronic lymphocytic thyroiditis and UBB hyperplasia, and do not stain like follicular or parafollicular cells, it is likely that the tumors do arise from UBB/solid cell nests. In this study, we provide additional evidence for this relationship, by demonstrating that SMECE stain strongly positive for p63, which is a new marker for UBB/solid cell nests.

Adult↗
PubMed2004

Molecular genotyping of medullary thyroid carcinoma can predict tumor recurrence.

Medullary thyroid carcinoma can have an aggressive behavior, and little is known about the molecular basis for clinical outcome. Defining risk of recurrent or metastatic disease is difficult, and it has been limited to clinical and pathologic features, such as advanced age, cervical lymph node metastases, and stage at presentation. Using microdissection and genotyping, we studied 11 cases of medullary carcinoma for allelic losses in a panel of known tumor suppressor genes. The tumor suppressor genes with the most frequent allelic losses were NF2, l-myc, and p53 (75%, 44%, and 44%, respectively). The average frequency of allelic loss across all tumors was 44% and was higher in tumors that recurred. A combination of previously described high-risk variables (increased patient age and cervical lymph node metastases) with the frequency of allelic loss yielded a high-risk group, in which 6 of 6 patients recurred, and a low-risk group, in which 0 of 5 patients recurred (P = 0.004). Frequency of allelic loss in tumor suppressor genes may provide a useful adjunctive prognostic test in medullary thyroid carcinoma.

Adolescent↗