Nomogram Including Elastography for Prediction of Contralateral Central Lymph Node Metastasis in Solitary Papillary Thyroid Carcinoma Preoperatively.

BACKGROUND: It is controversial whether contralateral prophylactic central neck dissection (PCND) should be performed for patients with solitary and clinical lymph node negative (cN0) papillary thyroid carcinoma (PTC) although routine ipsilateral PCND is required. OBJECTIVE: The aim of this study was to develop an improved nomogram including clinical features, ultrasound, and acoustic radiation force impulse (ARFI) elastography for the prediction of contralateral central lymph node metastasis (CLNM) in patients with solitary and cN0 PTC in the preoperative period. MATERIALS AND METHODS: A total of 340 patients were retrospectively included as the training cohort and 170 patients as the external validation cohort. Patients were grouped according to the pathological results of contralateral CLNM. The association between the clinical characteristics, ultrasound, and ARFI elastography and the risk for contralateral CLNM were analyzed. A nomogram was established based on the result of multivariable logistic analysis to predict the risk of contralateral CLNM, which was assessed by internal and external validation. RESULTS: CLNM was found in 213 patients (41.8%), among whom 142 (27.8%) had ipsilateral CLNM and 95 (18.6%) had contralateral CLNM (including 68 (13.3%) with bilateral CLNM). Multivariable analysis revealed that patients with younger age, male gender, larger tumor size, closer distance from the capsule, microcalcification, and larger SWVmean were independent predictors associated with the contralateral CLNM (P < 0.05), which was served as the basis of the nomogram. It showed good discrimination (C-index: 0.856) and calibration (χ2 = 9.028, P = 0.340, Hosmer-Lemeshow test) in the training cohort, and good discrimination was maintained in the external validation cohort (C-index: 0.792). CONCLUSION: The nomogram utilizing the features of ultrasound combined with ARFI elastography in preoperatively predicting the risk of contralateral CLNM in patients with solitary and cN0 PTC was established, which showed superior performance both in internal and external validation.

Monochromosome transfer and microarray analysis identify a critical tumor-suppressive region mapping to chromosome 13q14 and THSD1 in esophageal carcinoma.

Loss of chromosome 13q regions in esophageal squamous cell carcinoma (ESCC) is a frequent event. Monochromosome transfer approaches provide direct functional evidence for tumor suppression by chromosome 13 in SLMT-1, an ESCC cell line, and identify critical regions at 13q12.3, 13q14.11, and 13q14.3. Differential gene expression profiles of three tumor-suppressing microcell hybrids (MCH) and their tumorigenic parental SLMT-1 cell line were revealed by competitive hybridization using 19k cDNA oligonucleotide microarrays. Nine candidate 13q14 tumor-suppressor genes (TSG), including RB1, showed down-regulation in SLMT-1, compared with NE1, an immortalized normal esophageal epithelial cell line; their average gene expression was restored in MCHs compared with SLMT-1. Reverse transcription-PCR validated gene expression levels in MCHs and a panel of ESCC cell lines. Results suggest that the tumor-suppressing effect is not attributed to RB1, but instead likely involves thrombospondin type I domain-containing 1 (THSD1), a novel candidate TSG mapping to 13q14. Quantitative reverse transcription-PCR detected down-regulation of THSD1 expression in 100% of ESCC and other cancer cell lines. Mechanisms for THSD1 silencing in ESCC involved loss of heterozygosity and promoter hypermethylation, as analyzed by methylation-specific PCR and clonal bisulfite sequencing. Transfection of wild-type THSD1 into SLMT-1 resulted in significant reduction of colony-forming ability, hence providing functional evidence for its growth-suppressive activity. These findings suggest that THSD1 is a good candidate TSG.

Frequent decreased expression of candidate tumor suppressor gene, DEC1, and its anchorage-independent growth properties and impact on global gene expression in esophageal carcinoma.

Previous studies showed that expression of the novel candidate tumor suppressor gene, DEC1 (Deleted in Esophageal Cancer 1), is reduced in esophageal carcinoma and suppresses cancer cell growth in vitro and tumor growth in vivo in nude mice. This study shows that DEC1 gene expression was downregulated in 100% of 16 esophageal squamous cell carcinoma (ESCC) cell lines and 52 and 45%, respectively, of esophageal tumor specimens from Hong Kong and a high-risk ESCC region of Henan, China. Using epitope tagging, the DEC1 protein was localized to both the cytoplasm and nucleus of the cell. In 3D Matrigel culture, no significant difference in colony numbers formed was observed for DEC1 stable transfectants, as compared to vector-alone transfectant controls. However, significantly smaller colony sizes were observed for the DEC1 transfectants. In in vitro cell migration, invasion and soft agar assays of DEC1 transfectants, only the soft agar assay showed statistically significant differences in colony numbers with the vector-alone controls, indicating that DEC1 may be involved in anchorage-independent cell growth. In addition, the global gene expression affected by DEC1 in tumor-suppressive stable transfectants was investigated using cDNA oligonucleotide microarray hybridization. Three candidate genes, TFPI-2, GDF15 and DUSP6, were identified through this approach; they are downregulated in tumor segregants of DEC1 stable transfectants, ESCC cell lines and esophageal tumors and have a potential role in tumor growth and progression. These studies show that DEC1 is involved in esophageal cancer development and help elucidate its functional role in tumor development.