Detection of papillary thyroid carcinoma with serum protein profile analysis.

OBJECTIVE: To determine the sensitivity and specificity of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) for papillary thyroid carcinoma (PTC) detection. DESIGN: The SELDI-TOF-MS protein profiles of patients with PTC, patients with benign nodular disease (BND), and healthy controls were analyzed to determine the sensitivity and specificity of SELDI-TOF-MS assay for PTC detection. Data analysis was performed to process the spectral data and classify the disease status of the patients. SETTING: Academic tertiary care hospital. PATIENTS: Serum samples were collected prospectively from 7 patients with PTC, 8 patients with BND, and 7 healthy control volunteers. INTERVENTION: All patients diagnosed as having PTC or BND underwent thyroidectomy from October 21, 2004, to January 31, 2006. MAIN OUTCOME MEASURES: Twenty-two serum samples were analyzed. RESULTS: Most protein peaks resolved by the SELDI-TOF-MS assay were in the range of 1 to 20 kDa. Classification tree analysis based on peak expression distinguished patients with PTC from those with BND with 85.7% sensitivity and 100% specificity. Serum samples from patients with PTC differed most significantly from those of patients with BND by the underexpression of a protein peak at 11 101 Da. CONCLUSIONS: This pilot study demonstrates that proteomic analysis of serum protein profiles distinguishes patients with PTC from patients with BND with a high degree of sensitivity and specificity. Further investigation into the clinical utility of this technology in PTC biomarker detection and surveillance is warranted.

Correlation of intraoperative parathyroid hormone levels with parathyroid gland size.

OBJECTIVES: To study the relationship of intraoperative intact parathyroid hormone levels (iPTH) with parathyroid adenoma weight and volume in patients with primary hyperparathyroidism. METHODS: Retrospective evaluation of consecutive patients undergoing minimally invasive parathyroidectomy with iPTH measurement. Data collected include preoperative serum calcium, ionized calcium, and serum parathyroid hormone (PTH) levels, iPTH levels at baseline, 5 minutes, and 10 minutes, and parathyroid adenoma weight. Adenoma volume was calculated using an equation for the volume of a spheroid object. RESULTS: Thirty patients underwent minimally invasive parathyroidectomy with iPTH measurement for a single parathyroid adenoma between March 2004 and January 2006. There were 8 men and 22 women, with a mean age of 59.3 (range 26-92) years. A significant correlation between preoperative serum calcium and ionized calcium levels and parathyroid adenoma weight was identified (P = .0008 and P = .03, respectively). A significant correlation was also shown between baseline iPTH measurements and parathyroid adenoma volume (P = .03). There was no correlation between baseline iPTH levels and parathyroid adenoma weight. There was a significant correlation between parathyroid adenoma weight and percentage decrease of iPTH levels at 10 minutes compared to baseline (P = .04). CONCLUSION: Preoperative serum calcium and baseline iPTH levels may be useful in predicting parathyroid adenoma weight and volume, respectively. Adenoma weight may relate to the percentage decrease of iPTH levels at the 10-minute postparathyroidectomy interval.

Serum protein profile analysis following definitive treatment in patients with head and neck squamous cell carcinoma.

OBJECTIVE: To determine the sensitivity and specificity of surface-enhanced laser desorption and ionization time-of-flight mass spectrometry (SELDI-TOF-MS) assay for head and neck squamous cell carcinoma (HNSCC) disease surveillance. DESIGN: The SELDI-TOF-MS serum protein profiles of patients with HNSCC were analyzed to determine the sensitivity and specificity of the SELDI assay for HNSCC detection following definitive treatment. SETTING: Academic research. PATIENTS: Thirty-two patients with previously untreated HNSCC. INTERVENTION: Serum samples were collected prospectively at 3-month intervals following treatment during a 24-month follow-up period. MAIN OUTCOME MEASURES: Ninety-three serum samples were analyzed. RESULTS: The SELDI-TOF-MS identified protein peaks in the range of 0 to 100 kDa. Classification tree analysis based on peak expression distinguished pretreatment from 6-month posttreatment samples with 75.0% sensitivity and 87.5% specificity. Samples collected at 3 months following treatment did not significantly differ from pretreatment samples. Serum samples from patients who were disease free at 6 months or longer following treatment differed from matched pretreatment samples by the overexpression of a protein peak at 6495 Da, while serum samples from patients with recurrence differed from matched pretreatment samples by the underexpression of a protein peak at 4493 Da. CONCLUSIONS: Proteomic analysis of serum protein profiles distinguishes pretreatment and posttreatment samples from patients with HNSCC with a high degree of sensitivity and specificity. After 6 months, serum protein profiles seem to have distinct differences in peak expression based on disease status. Further investigation of the clinical usefulness of this technology in HNSCC detection and surveillance is warranted.

Association of nuclear, cytoplasmic expression of galectin-3 with beta-catenin/Wnt-pathway activation in thyroid carcinoma.

OBJECTIVES: To characterize the localization of galectin-3 in benign and malignant thyroid neoplasms and to correlate this with alterations in beta-catenin and cyclin D1 expression. DESIGN: Immunohistochemical study of 116 paraffin-embedded archival specimens from 113 patients who had undergone thyroidectomy and tissue placed into a commercially available tissue microarray. SETTING: Tertiary care hospital. INTERVENTIONS: Thyroid tissue microarrays were stained by standard immunohistochemical protocols with monoclonal antibodies against galectin-3, beta-catenin, and cyclin D1. MAIN OUTCOME MEASURES: Nuclear and cytoplasmic expression of galectin-3 was correlated with clinical parameters, beta-catenin, and cyclin D1 expression. RESULTS: Both cytoplasmic (56%) and nuclear (42%) galectin-3 expression was observed in most malignant neoplasms but was absent in benign thyroid specimens (P<.001). Among carcinomas, cytoplasmic galectin-3 expression was observed in papillary thyroid carcinomas (82%) and follicular (33%) and medullary (9%) carcinomas but was absent in anaplastic carcinomas (P<.001). Galectin-3 nuclear expression was observed in papillary thyroid carcinomas (62%) and follicular carcinomas (33%) but was undetectable in medullary, anaplastic carcinomas (P<.001). Cytoplasmic but not nuclear galectin-3 was inversely correlated with American Joint Committee on Cancer TNM stage (P = .02). There was a strong correlation between cytoplasmic and nuclear beta-catenin expression and both nuclear (P = .04) and cytoplasmic (P = .003) galectin-3 expression. Similarly, there was a strong association between galectin-3 nuclear (P<.001) and cytoplasmic (P<.001) expression and cyclin D1 expression. CONCLUSION: Cytoplasmic and nuclear galectin-3 expression seem to be associated with activation of the Wnt-signaling pathway in well-differentiated thyroid neoplasms, suggesting that galectin-3 plays a role in thyroid carcinogenesis.

Subjective headache before and after endoscopic sinus surgery.

BACKGROUND: The aim of this study was to show the effect of endoscopic sinus surgery on subjective headache scores in patients diagnosed with chronic rhinosinusitis (CRS) with or without nasal polyps. METHODS: We performed a retrospective analysis of prospectively collected data from 201 patients over a 2-year period. Headache and Sino-Nasal Outcomes Test (SNOT-20) mean scores were compared preoperatively and 2 years postoperatively on patients diagnosed with CRS with or without nasal polyps. RESULTS: Two hundred one patients underwent surgical management of CRS with or without nasal polyps over a 3-year period. One hundred four patients were men and 97 were women, with a mean age of 49 (range, 18-80 years) years. Polyps were present in 78 patients with CRS. The mean subjective headache score based on a 0-10 visual analog scale improved from 4.7 preoperatively to 0.8 2 years postoperatively (p < 0.0001). The mean headache score of 123 patients without polyps was larger compared with 78 patients with polyps (5.1 versus 4.1, respectively; p < 0.05). As previously reported, the mean overall preoperative and postoperative SNOT-20 scores were 28.7 and 6.7, respectively (p < 0.0001). CONCLUSION: Headache is a common symptom with CRS, present in 73.6% of our patients undergoing functional endoscopic sinus surgery for CRS with or without nasal polyps. An overall decrease in mean headache scores was noted at 2-year follow-up.