CXCR4 expression in papillary thyroid carcinoma: induction by nitric oxide and correlation with lymph node metastasis

<p>Abstract</p> <p>Background</p> <p>Metastasis to regional lymph nodes is a common step in the progression of cancer. Recent evidence suggests that tumor production of CXCR4 promotes lymph node metastasis. Nitric oxide (NO) may also increase metastatic ability in human cancers.</p> <p>Methods</p> <p>Nitrite/nitrate levels and functional CXCR4 expression were assessed in K1 and B-CPAP papillary thyroid carcinoma (PTC) cells after induction and/or inhibition of NO synthesis. CXCR4 expression was also analyzed in primary human PTC. The relationship between nitrotyrosine levels, which are a biomarker for peroxynitrate formation from NO in vivo, CXCR4 expression, and lymph node status was also analyzed.</p> <p>Results</p> <p>Production of nitrite/nitrate and functional CXCR4 expression in both cell lines was increased by treatment with the NO donor DETA NONOate. The NOS inhibitor L-NAME eliminated this increase. Positive CXCR4 immunostaining was observed in 60.7% (34/56) of PTCs. CXCR4 expression was significantly correlated with nitrotyrosine levels and lymph node metastasis in human PTC.</p> <p>Conclusion</p> <p>Our data indicate that NO stimulates CXCR4 expression in vitro. Formation of the NO biomarker nitrotyrosine was also correlated with CXCR4 expression and lymph node metastasis in human PTC. NO may induce lymph node metastasis via CXCR4 induction in papillary thyroid carcinoma.</p

Biological Behavior of Papillary Carcinoma of the Thyroid Including Squamous Cell Carcinoma Components and Prognosis of Patients Who Underwent Locally Curative Surgery

Thyroid carcinoma showing squamous differentiation throughout the entire lesion is diagnosed as squamous cell carcinoma of the thyroid (SCCT) in the WHO classification. This entity is a rare disease and shows a dire prognosis; however, squamous differentiation is more frequently detected in only a portion of papillary thyroid carcinoma. In this paper, we present our experience of 10 patients (8 primary lesions and 2 with recurrence in the lymph nodes) with papillary thyroid carcinoma having an SCC component (PTC-SCC). Only 3 of 8 primary lesions (38%) and none of the 2 recurrent nodes were preoperatively diagnosed as or suspected of having SCC components. All 10 patients underwent locally curative surgery. To date, 3 patients have died of carcinoma, and 2 had distant metastasis at diagnosis or had an undifferentiated carcinoma component. The other 7 are currently alive 5 to 43 months after diagnosis. Systemic adjuvant therapy after the detection of recurrence was effective for 2 patients. It is possible that some PTC-SCC patients without distant metastasis who undergo locally curative surgery can survive for a prolonged period and adjuvant therapies can be effective for local and distant recurrences

Prognosis of Patients with Papillary Thyroid Carcinoma Located in One Lobe Showing Lateral Node Metastasis in the Contralateral but Not Ipsilateral Compartment

Papillary thyroid carcinoma (PTC) frequently metastasizes to the lymph node in lateral compartment, which can often be detected on preoperative ultrasonography (N1b). However, PTC located in one lobe showing contralateral but not ipsilateral N1b is not common. We analyzed the clinicopathological features and prognosis of 13 patients with PTC limited in one lobe showing contralateral but not ipsilateral N1b. Sizes of the primary lesions ranged from 0.8 cm to 3.0 cm and only 2 tumors showed extrathyroid extension. Metastatic lateral node measured from 0.6 to 3.1 cm. Ten patients showed pathological central node metastasis and 5 had minute PTC lesions in the contralateral lobe. However, 3 patients did not show either of these. None of the patients have developed carcinoma recurrence or died of carcinoma to date. Taken together, PTC located in one lobe with contralateral but not ipsilateral N1b is rare and generally shows an indolent behavior. Although most patients had central node metastasis and/or minute PTC lesions in the contralateral lobe, it is also possible for carcinoma cells to metastasize directly from primary lesions to the contralateral lateral node. Total thyroidectomy with central node dissection and therapeutic MND of the contralateral compartment may be an acceptable surgical design and bilateral MND might not be mandatory

Clinical Study Clinical Significance and Prognostic Impact of Subcutaneous or Intrastrap Muscular Recurrence of Papillary Thyroid Carcinoma

Subcutaneous or intrastrap muscular (SIM) recurrence is rare in papillary thyroid carcinoma (PTC) patients, and its clinical significance remains unclear. We analyzed 29 patients with PTC who showed SIM recurrence in order to elucidate this issue. The incidence of patient age 55 years or older at initial surgery, extrathyroid extension, and clinically detected lymph node metastasis was 83%, 35%, and 46%, respectively. After surgical dissection, 17% of patients showed repeated SIM recurrence. Distant recurrence was detected in 45% of patients and was more likely to occur in patients with high-risk clinicopathological features. In all but one patient in this series, distant recurrence was detected at the same time or after the detection of SIM recurrence. Three patients died of PTC, but none of these patients died of the development of recurrent SIM lesions. These findings suggest that although SIM recurrence is a rare event and is not fatal, it is a predictor of distant recurrence especially in patients with high-risk clinicopathological features. Careful followup is recommended for such patients