Pralsetinib as neoadjuvant therapy for RET-Altered differentiated thyroid cancer: Two case reports.

BACKGROUND: 5-10% of thyroid cancers are at locally advanced stage. Neoadjuvant targeted therapy will likely create surgical opportunities for these patients with unresectable or borderline resectable tumors. Pralsetinib, a RET inhibitor, has been approved for advanced or metastatic RET-altered thyroid cancer. However, there is no evidence on the efficacy of pralsetinib as neoadjuvant therapy in locally advanced RET-altered thyroid cancer. CASE REPORT: Two patients with locally advanced pappilary thyroid carcinoma (PTC) were treated with pralsetinib (400 mg daily) to reduce tumor size and increase the chance of R0 resection. Both PTCs, characterized by RET-fusion, underwent successful R0 resection without major surgical complications after 4-months neoadjuvant pralsetinib. CONCLUSION: There is a potential for pralsetinib as a neoadjuvant treatment in PTC with RET-fusion.

Pediatric acute heart failure caused by endocardial fibroelastosis mimicking dilated cardiomyopathy: A case report.

BACKGROUND: Endocardial fibroelastosis (EFE) is a diffuse endocardial collagen and elastin hyperplasia disease of unknown etiology, which may be accompanied by myocardial degenerative changes leading to acute or chronic heart failure. However, acute heart failure (AHF) without obvious associated triggers is rare. Prior to the report of endomyocardial biopsy, the diagnosis and treatment of EFE are highly susceptible to being confounded with other primary cardiomyopathies. Here, we report a case of pediatric AHF caused by EFE mimicking dilated cardiomyopathy (DCM), with the aim of providing a valuable reference for clinicians to early identify and diagnose EFE-induced AHF. CASE SUMMARY: A 13-mo-old female child was admitted to hospital with retching. Chest X-ray demonstrated enhanced texture in both lungs and an enlarged heart shadow. Color doppler echocardiography showed an enlarged left heart with ventricular wall hypokinesis and decreased left heart function. Abdominal color ultrasonography revealed a markedly enlarged liver. Pending the result of the endomyocardial biopsy report, the child was treated with a variety of resuscitative measures including nasal cannula for oxygen, intramuscular sedation with chlorpromazine and promethazine, cedilanid for cardiac contractility enhancement, and diuretic treatment with furosemide. Subsequently, the child's endomyocardial biopsy report result was confirmed as EFE. After the above early interventions, the child's condition gradually stabilized and improved. One week later, the child was discharged. During a 9-mo follow-up period, the child took intermittent low-dose oral digoxin with no signs of recurrence or exacerbation of the heart failure. CONCLUSION: Our report suggests that EFE-induced pediatric AHF may present in children over 1 year of age without any apparent precipitants, and that the associated clinical presentations are grossly similar to that of pediatric DCM. Nonetheless, it is still possible to be diagnosed effectively on the basis of the comprehensive analysis of auxiliary inspection findings before the result of the endomyocardial biopsy is reported.

FMNL1 Exhibits Pro-Metastatic Activity via CXCR2 in Clear Cell Renal Cell Carcinoma.

Formin-like (FMNL) proteins are responsible for cytoskeletal remodeling and have been implicated in the progression and spread of human cancers. Yet the clinical significance and biological function of FMNL1 in clear cell renal cell carcinoma (ccRCC) remain unclear. In this study, the expression of FMNL1 in ccRCC and its clinical value were determined by tissue microarray-based IHC and statistical analyses. The role of FMNL1 in ccRCC metastasis and the underlying mechanism were investigated via in vitro and in vivo models using gene regulation detection, ChIP, Luciferase reporter assays, and rescue experiments. We show that FMNL1 is upregulated in ccRCC and exhibits pro-metastatic activity via induction of CXCR2. High expression of FMNL1 is significantly correlated with advanced tumor stage, higher pathological tumor grade, tumor metastasis, and unfavorable prognosis in two independent cohorts containing over 800 patients with ccRCC. The upregulation of FMNL1 in ccRCC is mediated by the loss of GATA3. Ectopic expression of FMNL1 promotes, whereas FMNL1 depletion inhibits cell migration in vitro and tumor metastasis in vivo. The FMNL1-enhanced cell mobility is markedly attenuated by the knockdown of CXCR2. Further studies demonstrate that FMNL1 increases the expression of CXCR2 via HDAC1. In clinical samples, FMNL1 expression is positively associated with CXCR2, and is negatively connected to GATA3 expression. Collectively, our data suggest FMNL1 serve as a potential prognostic factor and function as an oncogene. The axis of GATA3/FMNL1/CXCR2 may present a promising therapeutic target for tumor metastasis in ccRCC.

Amycolatopsis anabasis sp. nov., a novel endophytic actinobacterium isolated from roots of Anabasis elatior.

A novel endophytic actinobacterium, designated strain EGI 650086T, was isolated from the roots of Anabasis elatior (C.A.Mey.) Schischk. collected in Xinjiang, north-west China. The taxonomic position of the strain was investigated using a polyphasic taxonomic approach. Growth occurred at 15-40 °C, pH 6.0-8.0 and in the presence of 0-6 % NaCl (w/v). Phylogenetic analysis based on 16S rRNA gene sequence and concatenation of 22 protein marker genes revealed that strain EGI 650086T formed a monophyletic clade within the genus Amycolatopsis and shared the highest sequence similarities with Amycolatopsis nigrescens JCM 14717T (97.1 %) and Amycolatopsis sacchari DSM 44468T (97.0 %). Sequence similarities with type strains of other species of the genus Amycolatopsis were less than 97.0 %. The average nucleotide identity and DNA-DNA hybridization values between strain EGI 650086T and the reference strains were 78.1-79.8 % and 22.1-23.0 %, respectively. The genome of strain EGI 650086T was 10.9 Mb, with a DNA G+C content of 70.1 mol%. The diagnostic diamino acid in the peptidoglycan was meso-diaminopimelic acid. The major whole-cell sugars contained arabinose, galactose, glucose and ribose. The predominant menaquinones were MK-9 (H4) and MK-9 (H2). Major fatty acids were iso-C16 : 0 and summed feature 4 (iso-C17 : 1 I and/or anteiso-C17 : 1 B). The polar lipid profile of strain EGI 650086T included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, hydroxy-phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannosides, two unknown phospholipids, an unknown glycolipid and an unknown lipid. Polyphasic taxonomic characteristics indicated that strain EGI 650086T represents a novel species of the genus Amycolatopsis, for which the name Amycolatopsis anabasis sp. nov. is proposed. The type strain is EGI 650086T (=KCTC 49044T=CGMCC 4.7188T).

PRMT6 promotes endometrial cancer via AKT/mTOR signaling and indicates poor prognosis.

Arginine methylation plays essential roles in post-transcriptional modification and signal transduction. Dysregulation of protein arginine methyltransferases (PRMTs) has been reported in human cancers, yet the expression and biological function of PRMT6 in endometrial cancer (EMC) remains unclear. Here, we show that PRMT6 is upregulated in EMC and exhibits oncogenic activities via activation of AKT/mTOR pathway. The expression of PRMT6 in EMC is much higher than that in the adjacent nontumorous tissues. Elevated PRMT6 expression is significantly associated with higher histological tumor grade and unfavorable prognosis in two independent cohorts consisting of a total of 564 patients with EMC. In vitro data demonstrate that PRMT6 expression was identified as a downstream target of miR-372-3p. Ectopic expression of miR-372-3p downregulates PRMT6. Overexpression of PRMT6 promotes EMC cell proliferation and migration, whereas knockdown of PRMT6 leads to opposite phenotypes. Mechanistically, PRMT6 induces the phosphorylation of AKT and mTOR in EMC cells. Inhibition of AKT/mTOR signaling by MK2206 or rapamycin attenuates the PRMT6-mediated EMC progression. In clinical samples, high expression of PRMT6 was correlated to low expression of miR-372-3p and high expression of phosphorylated AKT. Collectively, our findings suggest PRMT6 may function as an oncogene to promote tumor progression, and be of prognostic value to predict disease-free survival of patients with EMC. The newly identified miR-372-3p/PRMT6/AKT/mTOR axis represents a new promising target for EMC management.

An E2F1/DDX11/EZH2 Positive Feedback Loop Promotes Cell Proliferation in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) accounts for one of the leading causes of cancer-related death, and is attributed to the dysregulation of genes involved in genome stability. DDX11, a DNA helicase, has been implicated in rare genetic disease and human cancers. Yet, its clinical value, biological function, and the underlying mechanism in HCC progression are not fully understood. Here, we show that DDX11 is upregulated in HCC and exhibits oncogenic activity via EZH2/p21 signaling. High expression of DDX11 is significantly correlated with poor outcomes of HCC patients in two independent cohorts. DDX11 overexpression increases HCC cell viabilities and colony formation, whereas DDX11 knockdown arrests cells at G1 phase without alteration of p53 expression. Ectopic expression of DDX11 reduces, while depletion of DDX11 induces the expression of p21. Treatment of p21 siRNA markedly attenuates the cell growth suppression caused by DDX11 silence. Further studies reveal that DDX11 interacts with EZH2 in HCC cells to protect it from ubiquitination-mediated protein degradation, consequently resulting in the downregulation of p21. In addition, E2F1 is identified as one of the upstream regulators of DDX11, and forms a positive feedback loop with EZH2 to upregulate DDX11 and facilitate cell proliferation. Collectively, our data suggest DDX11 as a promising prognostic factor and an oncogene in HCC via a E2F1/DDX11/EZH2 positive feedback loop.

Xenotropic and polytropic retrovirus receptor 1 (XPR1) promotes progression of tongue squamous cell carcinoma (TSCC) via activation of NF-κB signaling.

BACKGROUND: Xenotropic and polytropic retrovirus receptor 1 (XPR1), a previously identified cellular receptor for several murine leukemia viruses, plays a role in many pathophysiological processes. However, the role of XPR1 in human cancers has not yet been characterized. METHODS: Real-time PCR and western blotting assay were used to measure the expression of XPR1 in tongue squamous cell carcinoma (TSCC) tissues. Expression of XPR1 and p65 in clinical specimens was analyzed using immunohistochemical assay. The function of XPR1 on progression of TSCC was explored using in vitro and in vivo experiments. The molecular mechanism by which XPR1 helps to cancer progression was investigated by luciferase reporter activity, ELISA, PKA activity assay, immunofluorescence, western blotting and qPCR assay. RESULTS: Herein, we find that XPR1 is markedly upregulated in TSCC tissues compared to normal tongue tissues. High expression of XPR1 significantly correlates with the malignant features and poor patient survival in TSCC. Ectopic expression of XPR1 increases, while silencing of XPR1 reduces the proliferation, invasion and anti-apoptosis capacities of TSCC cells. Importantly, silencing of XPR1 effectively inhibits the tumorigenecity of TSCC cells. Moreover, we identified that XPR1 increased the concentration of intracellular cAMP and activated PKA. Thus, XPR1 promoted phosphorylation and activation of NF-κB signaling, which is required for XPR1-mediated oncogenic roles and significantly correlates with XPR1 expression in clinical specimens. CONCLUSIONS: These findings uncover a critical role of XPR1 in TSCC progression via activation of NF-κB, and suggest that XPR1 might be a potential prognostic marker or therapeutic target.

Trends in clinical features and survival of oral cavity cancer: fifty years of experience with 3,362 consecutive cases from a single institution.

BACKGROUND: Global data demonstrate minimal improvement in the survival rate for oral cavity cancer (OCC) patients. We wished to know whether or not clinical features and survival rate have changed over time for OCC patients receiving initial treatment and follow-up at a large cancer center in China. METHODS: Clinical features and survival data were collected on patients diagnosed during the successive decades of 1960-1969 (n=253), 1970-1979 (n=497), 1980-1989 (n= 659), 1990-1999 (n=793), and 2000-2009 (n=1,160) at the Sun Yat-sen University Cancer Center. RESULTS: Over time, the overall 5-year survival rate for OCC patients was 52.0%. According to tumor localization, this rate was 71.4% for lip cancer, 56.3% for oral tongue cancer, and 42.7% for other parts of the oral cavity. From the 1960s to the 2000s, the 5-year survival rate steadily improved from 47.8% to 55.6% (P<0.001). Survival steadily decreased with age and was higher for women than for men in the 3 most recent decades. The survival rate for male patients was constant over time, while the rate for female patients improved dramatically. Obvious trends in clinical features over time included the following: increasing age of patients, increasing proportions of localized disease at diagnosis, decreasing proportions of diagnoses of lip cancer, decreasing proportions of diagnoses of squamous cell carcinoma, and decreasing proportions of non-surgical treatment approaches. CONCLUSION: The survival rate has steadily improved for OCC patients at this cancer center.

Synchronous colorectal cancer and multiple myeloma with chest wall involvement: Is this a coincidence?

Multiple primary malignant neoplasms (MPMNs) are rare malignant neoplasms that simultaneously or successively occur in the same patient as 2 or more primary malignancies. Currently, an increasing number of cases are being reported. In general, MPMNs more commonly occur as 2 solid tumors or 2 hematological malignancies. Cases of MPMN that involve a solid tumor and a hematological malignancy are rare. Here, we report a case of synchronous colorectal cancer (CRC) and multiple myeloma (MM) with chest wall involvement. After reviewing the literature, we believe that there may be a distinct syndrome involving CRC and MM. The patient in our case study suffered refractory anemia following surgery and 2 cycles of chemotherapy. Initially, the anemia was considered to be a common manifestation of CRC in this patient. Interestingly, although he received a blood transfusion, his hemoglobin levels remained low. He later developed hematuria, proteinuria, multiple osteoporosis in the costal bones, and thrombocytopenia. These new symptoms drew our attention, and we considered a diagnosis of synchronous primary CRC and MM, with the anemia as a symptom of MM. Based on the results of a bone marrow aspirate, MM was confirmed. Therefore, when CRC is associated with refractory anemia, we should not only assume that anemia is a classical symptom of CRC, a result of chronic blood loss, nutritional deficiencies, or myelosuppression due to chemotherapy, but we should also consider that it may reflect the possibility of a coexisting hematologic malignancy. As the treatment of these 2 malignancies is different, early diagnosis and treatment based on definitive diagnosis as early as possible will be beneficial to overall prognosis.

Rare coexistence of mediastinal hepatoid adenocarcinoma, idiopathic azoospermia and horseshoe kidney: a case report and review of the literature.

Hepatoid adenocarcinoma (HAC) is the term proposed for a special type of extrahepatic tumors, which is similar to the hepatocellular carcinoma (HCC) both in the histopathology and immunohistochemistry. HAC has been observed in the stomach, colon, pancreas, gall bladder, lung and female genital tract, but rarely in the mediastinum. Now we describe a case of a 28-year-old Chinese male with primary mediastinal HAC with lung and liver metastasis. In this patient, HAC was associated with horseshoe kidney and idiopathic nonobstructive azoospermia. It seemed derivation abnormalities during organogenesis in the embryo stage played a significant role in the pathogenesis of HAC, horseshoe kidney and idiopathic nonobstructive azoospermia. Even the pathogenesis was still unknown; it may merit consideration of HAC together with horseshoe kidney and idiopathic nonobstructive azoospermia as a syndrome rather than as a spectrum of coincidental diseases. Furthermore, we found the HAC is a neoplasm with unfavorable outcomes despite aggressive and multi-protocol strategies. The serum alpha fetoprotein (AFP) should be regarded as a useful marker for diagnostic purposes and therapeutic response evaluation of HAC.

A Meta-analysis of Carbon Nanoparticles for Identifying Lymph Nodes and Protecting Parathyroid Glands during Surgery.

OBJECTIVE: To investigate the ability of carbon nanoparticles (CNs) to identify lymph nodes and protect parathyroid glands during thyroid cancer surgery. DATA SOURCES: English and Chinese literature in PubMed, ClinicalTrials.gov, EMBASE, the Cochrane Database of Systematic Reviews, the China Biology Medicine Database, the China Master's and Doctoral Theses Full-Text Database, the China National Knowledge Infrastructure, the WANFANG database, and the Cqvip database (from January 2009 to July 2014). REVIEW METHODS: Studies were included if they were randomized controlled trials or nonrandomized controlled trials for thyroidectomy and central neck dissections that compared the use of CNs with methylene blue or a blank control in patients undergoing initial thyroid cancer surgery. The primary outcomes were the number of retrieved central lymph nodes and the accidental parathyroid removal rate. RESULTS: This meta-analysis identified 11 randomized controlled trials and 4 nonrandomized controlled trials comprising 1055 patients. Compared with the outcomes of the blank controls, the use of CNs resulted in an average of 2.71 more lymph nodes removed per patient (weighted mean difference = 2.71, 95% confidence interval [CI] = 1.68-3.74, P < .001), a 23% lower rate of accidental parathyroid removal (odds ratio = 0.23, 95% CI = 0.10-0.54, P = .0008), and similarly reduced rates of transient hypoparathyroidism and hypocalcemia. Compared with methylene blue, the use of CNs resulted in an average of 1.50 more lymph nodes removed per patient (weighted mean difference = 1.50, 95% CI = 0.11-2.89, P = .03) and a 5% reduction in the rate of accidental parathyroid removal (odds ratio = 0.05, 95% CI = 0.01-0.29, P = .0007). CONCLUSION: CNs partially improve the extent and accuracy of neck dissection and preserve the normal anatomic structure and physiologic function of the parathyroid glands during thyroid cancer surgery.

Treatment and prognosis in sinonasal mucosal melanoma: A retrospective analysis of 65 patients from a single cancer center.

BACKGROUND: The purpose of this study was to evaluate the outcome in sinonasal mucosal melanoma (SMM). METHODS: A retrospective analysis of clinicopathological data from January 1976 to December 2005 was performed. Survival curve, univariate, and multivariate analyses were undertaken. RESULTS: Sixty-eight patients with SMM were enrolled; 3 patients refused treatment. The 3-year and 5-year overall survival (OS) rates in the remaining 65 cases of SMM were 36.5% and 29.7%, respectively. Patients who underwent surgery had better 3-year and 5-year OS rates than those treated without surgery (40.7% and 34.1% vs 21.4% and 14.3%, respectively), and the same was true for patients treated with and without biotherapy (58.2% and 50.9% vs 30.0% and 23.4%, respectively). Distant metastasis at presentation was associated with a worse prognosis. Those patients managed with multimodality treatment had better OS rates. CONCLUSION: The prognosis in SMM is poor, particularly for those with distant metastasis or without surgery. Multimodality treatment may improve survival.

[Laryngeal reconstruction by complex hyoid bone flap after frontal partial laryngectomy].

OBJECTIVE: The aim of this study was to describe a new technique of combined hyoid bone and thyrohyoid membrane flap in laryngeal reconstruction after tumor resection, and to evaluate outcome. METHODS: Six patients requiring an frontal partial laryngectomy for cancer were enrolled between September 2008 and August 2012. RESULTS: Nasogastric feeding was initiated within 24 hours. The mean times to swallow batter, ability to drink water and removal of the nasogastric tube were 2.6, 5.5 and 6.3 days. All patients had good respiratory function. There were no deaths, and no reports of postoperative dyspnea or dysphagia. The vocal quality was satisfactory, slightly deeper and raspy, and the volume was weak when calling. The final follow-up assessment was in August 2012, and the overall mean follow-up period was 29.5months, range 14 to 47 months. Case two subsequently underwent total laryngectomy for recurrence in the paraglottic space, but there was no evidence of further tumor recurrence at the final assessment. CONCLUSIONS: The combined muscle-pedicle hyoid bone and thyrohyoid membrane flap is a reliable graft for one-stage repair of laryngotracheal defects, providing effective repair of the mucosa and cartilage support. Vocal quality, swallowing function and ventilation after the procedure were favorable.

[Fine-needle aspiration with measurement of parathyroid hormone levels in thyroidectomy].

OBJECTIVE: Hypoparathyroidism is one of the most serious complications of thyroidectomy. It is important to identify the parathyroid glands during thyroidectomy. In order to find an economic, simple and less traumatic way to identify the parathyroid glands and testify its feasibility, fine-needle aspiration of suspected parathyroid tissue was used to measure the parathyroid hormone (PTH) levels during the surgical procedure. METHODS: From Nov. 2011 to Apr. 2012, 50 patients were recruited for thyroid surgery in the Sun Yat-sen University Cancer Centre. During surgery, fine-needle aspiration of suspected tissues, including parathyroid gland, thyroid gland, muscle, fat tissue, and lymph node, was performed, the PTH levels were measured. In addition, the tissues above-mentioned were taken to pathological examination. Statistical processing was adopted to determine the sensitivity and specificity of intraoperative fine-needle aspiration with measurement of PTH level in finding the pathology of the parathyroid gland. RESULTS: There were 237 tissues from 50 patients in total, and 45 of them were certified as the parathyroid glands by pathology. Intra-operative PTH (ioPTH) of the tissues in forty-four cases were higher than 600 ng/L, ioPTH of the tissues in one case was lower than 600 ng/L, and it was 160 ng/L. The highest ioPTH in other cases was 537.7 ng/L. The sensitivity was 97.8%. The specificity was 100%. The difference between the sensitivity and the specificity of two groups was not statistically significant, and P > 0.05. The level of PTH of parathyroid gland were much higher than other tissues, and P < 0.001. CONCLUSIONS: The level of ioPTH of parathyroid gland were far higher than thyroid, muscle, fat, lymph node. It is an economic, fast and less traumatic way to identify the parathyroid gland by using the fine-needle aspiration of the parathyroid tissue with measurement of PTH levels. The sensitivity and the specificity are high. It can be used in the thyroidectomy to identify the parathyroid glands.

Influence of pathologic complete response to neoadjuvant chemotherapy on long-term survival of patients with advanced head and neck squamous cell carcinoma.

OBJECTIVE: The aim of this study was to analyze whether pathologic complete response (PCR) to neoadjuvant chemotherapy (NAC) affected long-term survival in advanced head and neck squamous cell carcinoma (HNSCC) patients. MATERIALS: All patients with advanced HNSCC were previously untreated and underwent NAC followed by surgery. The 5-year overall survival, disease-free survival, local control rate, and reasons for treatment failure were analyzed. RESULTS: A total of 101 cases were included, and the response rate to NAC was 67.3%, including 17 patients (16.8%) who achieved PCR. The 5-year overall survival (OS) of the PCR group (82.4%; histologically complete response group [HCG]) was higher than that of the pathologic incomplete responder group (45.4%; histologically incomplete response group [HICG]) (P = 0.045). No statistically significant difference was noted between the two groups in terms of local recurrence and nodal recurrence, but the local control rate in HCG (88.2%) was higher than that in HICG (62.7%) (P = 0.034). CONCLUSIONS: Achieving PCR could improve locoregional control and long-term survival in patients with advanced HNSCC.

[Use of a linear stapler device in total laryngectomy].

OBJECTIVE: To evaluate the value of using a linear stapler device for the closure of the pharynx during total laryngectomy. METHODS: Sixteen total laryngectomies were performed between August 2010 and December 2011, during the operation, the TA 60 linear stapler was used for pharyngeal closure. Among these patients, two patients had the history of pre-operative radiotherapy, four patients recurred after radiotherapy, ten patients were treated for the first time. 100 ml methylene blue was injected into the newly closed laryngopharyngeal cavity through the nasopharyngeal breather pipe for checking up whether it was watertight or not. RESULTS: Among the sixteen patients, methylene blue leakage from the mucosal joint of the gular cavity closed by the stapler were not found in fifteen patients, it was only found in one patient. The transudatory places were sutured with absorbable Vicryl sutures. This patient healed well without pharyngocutaneous fistula. Negative surgical margins were achieved in all patients. No patient needed to be transferred to open surgery. Using a linear stapler device in total laryngectomy, 45 minutes could be saved as compaired to manual suture. One patient developed a light pharyngocutaneous fistula. The incidence of pharyngocutaneous fistula was 6.25% (1/16). CONCLUSIONS: This stapled closed technique for pharyngoplasty is efficient, eliminates the risk of wound contamination, saves operation time and decreases the incidence of pharyngocutaneous fistula. This technique can be recommended as alternative for repairing the pharynx in patients undergoing total laryngectomy.

Expression TGM2 and BNIP3 have prognostic significance in laryngeal cancer patients receiving surgery and postoperative radiotherapy: a retrospective study.

BACKGROUND: This study was designed to determine the pattern and correlation between expression of the HIF-1α transcriptional targets TGM2 and BNIP3 in laryngeal cancer, and investigate the association of BNIP3 and TGM2 with clinical outcome in laryngeal squamous cell carcinoma (SCC) patients receiving postoperative radiotherapy. METHODS: Immunostaining with antibodies specific to BNIP3 and TGM2 was performed in formalin-fixed, paraffin-embedded specimens from 148 laryngeal SCC patients. BNIP3 and TGM2 expression was scored as high or low, based on the number of tumor cells stained and the staining intensity. All patients received postoperative radiotherapy. Patient follow up and clinicopathological data were compared using the Chi-squared test, univariate and multivariate analyses, and survival curves were generated using the Kaplan-Meier method and log-rank test. RESULTS: The 3, 5 and 10-year overall survival rates (OS) for all patients were 77.7%, 71.6%, 56.4%, respectively. Primary tumor site, T stage, overall stage, lymph-node metastasis, BNIP3 expression and TGM2 expression were significant prognostic factors for OS in univariate analysis. Negative cervical lymph nodes, high BNIP3 expression and low TGM2 expression were independent prognostic factors of improved OS in multivariate analysis. BNIP3 expression correlates with TGM2 expression in laryngeal SCC (P = 0.012). CONCLUSIONS: This study indicates that lymph-node metastasis, BNIP3 expression and TGM2 expression are independent prognostic factors in laryngeal SCC patients receiving postoperative radiotherapy. Further studies are required to investigate how BNIP3 and/or TGM2 influence the prognosis of laryngeal SCC patients treated with postoperative radiotherapy, and to determine how TGM2 and BNIP3 expression are regulated.

ZCCHC12, a potential molecular marker of papillary thyroid carcinoma: a preliminary study.

A gene expression profile analysis using an Affymetrix HG-U133 Plus 2.0 microarray with probes for 38,500 human full-length cDNAs was performed on a primary papillary thyroid carcinoma (PTC) and a nodular goiter (NG). ZCCHC12 was the gene with the most significant differential expression between PTC and NG, and this was verified using fluorescent quantitative PCR (FQ-PCR). A total of 9,485 genes were detected with a difference in transcription levels between PTC and NG. Of these, 2,098 were up-regulated with a signal log ratio (SLR) ≥ 1 and 1,714 were down-regulated with an SLR ≤ -1. Among these up-regulated and down-regulated genes, 12 genes were significantly up-regulated (SLR ≥ 5.0) and 6 genes were significantly down-regulated (SLR ≤ -5.0). The SLR of the ZCCHC12 gene was 8.8. The results of FQ-PCR showed that the medians of the log (ZCCHC12 RNA/GAPDH RNA) in PTC and NG were 0.73 and -1.68, respectively, and the difference between them was significant (P < 0.05). There were no significant correlations between the RNA levels of the ZCCHC12 gene and the clinicopathological and biochemical parameters of PTC in our pilot study. This study showed that a number of differentially expressed genes were discovered between PTC and NG. Significantly, the number of transcript copies of the ZCCHC12 gene in PTC was higher than in NG. The verified results of FQ-PCR were consistent with the microarray screening results. The ZCCHC12 gene may be a novel diagnostic molecular marker of PTC.

Treatment results and prognostic factors of patients undergoing postoperative radiotherapy for laryngeal squamous cell carcinoma.

Postoperative radiotherapy (PRT) is widely advocated for patients with squamous cell carcinomas of the head and neck that are considered to be at high risk of recurrence after surgical resection. The aims of this study were to evaluate the treatment outcomes of PRT for patients with laryngeal carcinoma and to identify the value of several prognostic factors. We reviewed the records of 256 patients treated for laryngeal squamous cell carcinoma between January 1993 and December 2005. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Log-rank test was employed to identify significant prognostic factors for DFS and OS. The Cox proportional hazards model was applied to identify covariates significantly associated with the aforementioned endpoints. Our results showed the 3-, 5-, and 10-year DFS for all patients were 69.9%, 59.5%, and 34.9%, respectively. The 3-, 5-, and 10-year OS rates were 80.8%, 68.6%, and 38.8%, respectively. Significant prognostic factors for both DFS and OS on univariate analysis were grade, primary site, T stage, N stage, overall stage, lymph node metastasis, overall treatment times of radiation, the interval between surgery and radiotherapy, and radiotherapy equipment. Favorable prognostic factors for both DFS and OS on multivariate analysis were lower overall stage, no cervical lymph node metastasis, and using 60Co as radiotherapy equipment. In conclusion, our data suggest that lower overall stage, no cervical lymph node metastasis, and using 60Co as radiotherapy equipment are favorable prognostic factors for DFS and OS and that reducing the overall treatment times of radiation to 6 weeks or less and the interval between surgery and radiotherapy to less than 3 weeks are simple measures to remarkably improve treatment outcome.

Elective neck dissection in clinical stage I squamous cell carcinoma of the tongue: Does it improve regional control or survival time?

The objective of this study was to evaluate whether elective neck dissection could improve regional control or survival time in clinical stage I squamous cell carcinoma of the oral tongue (OTSCC). This was a retrospective study of patients with surgical treatment between January 1991 and December 2003. A total of 131 patients were included in the study, and all of them received operation of the primary site, while 88 cases underwent selective neck dissection simultaneously including level I-III neck dissection in 49 patients and level I-V neck dissection in 39 patients. In all these cases, the rate of occult neck metastases was 23.7%. The 4-year local control rates in patients with only primary site treatment, patients with level I-III neck dissection and patients with level I-V neck dissection were 81.0%, 83.6% and 89.1%, respectively. By univariate analyse, neck dissection did not increase regional control rate, disease free survival (DFS) or overall survival (OS). Multivariate analyses showed that neck dissection was not an independent factor for DFS or OS. This study showed that the occult neck metastases rate was 23.7% in clinical stage I OTSCC. Elective neck dissection did not significantly improve regional control, DFS and OS in clinical stage I patients. There is a need for accurate and valid methods to select the patients who would benefit from elective neck treatment.