Guoxin Ren

Expression of Glut-1 in primary and recurrent head and neck squamous cell carcinomas, and compared with 2-[18F]fluoro-2-deoxy-D-glucose accumulation in positron emission tomography

The aim of the study was to investigate the pattern of glucose transporter-1 (Glut-1) expression in primary and recurrent head and neck squamous cell carcinomas (HNSCCAs) and the relation between Glut-1 expression and 2-[18F]fluoro-2-deoxy-D-glucose - positron emission tomography (FDG-PET). Standardised uptake values (SUVs) were used to evaluate FDG uptake by the tumour. Sections were stained immunohistochemically for Glut-1, which showed that high SUVs were seen in all HNSCCAs, and patients with higher T stage tumours or less well-differentiated tumours showed significantly higher SUVs than those with lower stage tumours or better-differentiated tumours (P=0.001 and 0.04, respectively). Glut-1 immunostaining was present in all cases. The Glut-1 staining index in primary HNSCCAs was significantly lower than that in recurrent HNSCCAs (P=0.03), and the index of better-differentiated tumours lower than that of poorly-differentiated tumours (P=0.02). However, there was no significant correlation between SUV(mean) and the Glut-1 staining index. In conclusion, our data suggest that high FDG uptakes were seen with overexpression of Glut-1 in primary and recurrent HNSCCAs. SUV(mean) was related to tumour T stage and grade of differentiation, which indicated that SUV was helpful in evaluating tumours. The expression of Glut-1 in recurrent HNSCCAs was higher than that in primary HNSCCAs, and in poorly-differentiated HNSCCAs higher than in better-differentiated HNSCCAs, which indicated that Glut-1 may have a useful role as a predictor for poor prognosis in HNSCCAs. However, there was no significant correlation between FDG accumulation and Glut-1 expression.

Neck dissection and post-operative chemotherapy with dimethyl triazeno imidazole carboxamide and cisplatin protocol are useful for oral mucosal melanoma

BackgroundOral mucosal melanoma (OMM) is a clinically rare disease with poor prognosis. Various treatment methods have been investigated with the aim of improving the prognosis. This study aimed to analyze the data of a single institution in the management of OMM.MethodsA total of 78 consecutive OMM patients were included in this retrospective study. The intraoral lesion was treated either by cryotherapy, surgery or both; the neck was treated by neck dissection or observation; post-operative chemotherapy with dimethyl triazeno imidazole carboxamide and cisplatin was performed in some patients. The Kaplan-Meier method was used for statistical analysis.ResultsAmong the 78 patients, there were 50 males and 28 females with an average age of 53.8 years (ranging from 27 to 85 years). The most common sites of OMM were the hard palate and gingiva. The main cause of death in OMM was distant metastasis. No significant difference was found between the intraoral/cervical lesion recurrence/post-operative distant metastasis and the intraoral lesion site/biopsy method/treatment method. The metastasis rate of cervical lymph node was high in the OMM patients, even in the patients with clinically negative necks. Cervical lesion recurrence was correlated with N stage and intraoral lesion recurrence. The survival period was longer in the patients with T3 staging, clinical stage III disease, with post-operative chemotherapy and without post-operative distant metastasis when compared to those patients with T4a staging, clinical stage IV disease, without post-operative chemotherapy and with post-operative distant metastasis.ConclusionsRadical surgery including wide intraoral resection and neck dissection is recommended for OMM patients. Post-operative chemotherapy may also be beneficial for both primary and recurrent OMM patients.

Prognostic factors of oral mucosal melanoma: histopathological analysis in a retrospective cohort of 82 cases.

To investigate the histopathological predictors of overall survival and metastatic failure of oral mucosal melanoma (OMM), of which the histopathological classification and microstaging has not been established.

Neck dissection for oral mucosal melanoma: Caution of nodular lesion

BACKGROUND Oral mucosal melanoma (OMM) often metastasizes to cervical nodes. A great number of studies have been conducted to evaluate the efficacy of neck dissection in the treatment of OMM, but considerable controversy remains in this field. PATIENTS AND METHODS The clinical features, treatments, and outcomes of 254 OMM patients were retrospectively analyzed from Jan. 1998 to Jul. 2012. Multivariate analysis was performed to identify the variables related to overall survival (OS). RESULTS Tumor size greater than 4 cm (p=0.01) and nodular types (p<0.0001) were independent prognostic factors for OS. Patients with nodular melanomas were more likely to have distant metastases than those with macular melanomas (p<0.0001). 164 Patients (65%) had CLN metastases. The multivariate analysis revealed that prophylactic neck dissection was an independent favorable factor for OS (p=0.0016) in patients with cN0 nodular melanomas; whereas radical neck dissection (p=0.03) in patients with positive CLN. Patients undergoing functional neck dissection were more likely to have neck recurrence (p<0.001). CONCLUSION(S) Nodular type is a dangerous signal to OMM. It is advisable for patients with cN0 nodular melanomas to have prophylactic neck dissection, close observation is recommended for patients with cN0 macular melanomas, and patients with positive CLN should undergo radical neck resection.

Mutation scanning of BRAF, NRAS, KIT, and GNAQ/GNA11 in oral mucosal melanoma: a study of 57 cases

BACKGROUND Recent advances in novel targeted therapies have created the need for molecular characterization of cancer to allow accurate personalized treatments. In this study, our aim was to investigate the incidence of activating mutations of oncogenes BRAF, NRAS, KIT, and GNAQ/GNA11 in oral mucosal melanoma. METHODS We analyzed a cohort of 57 oral mucosal melanoma samples, including 27 frozen samples and 30 formalin-fixed paraffin-embedded samples. The tumors were screened for hotspot mutations of BRAF (exon 15), NRAS (exons 2 and 3), KIT (exons 9, 11, 13, and 17), and GNAQ/GNA11 (exon 5) by high-resolution melting and direct sequencing. RESULTS In oral mucosal melanoma, 7.0% of tumors harbored KIT mutations and 3.5% harbored BRAF mutations, while classic BRAF V600E mutation was not detected. We found no mutations of NRAS or GNAQ/GNA11 in oral mucosal melanoma. CONCLUSION We demonstrated that driver mutations are rare in mutational hotspots of BRAF, NRAS, KIT, and GNAQ/GNA11 in oral mucosal melanoma. The majority of patients will not benefit from KIT and BRAF inhibitors.

Head and neck rhabdomyosarcoma in adults.

AimThe purpose of this study was to explore the treatment and prognosis of head and neck rhabdomyosarcoma (RMS) in adults. MethodsFifty-nine patients with head and neck RMS in adults (AHNRMS) treated in one institution were selected. Multivariate analysis was used to evaluate the various variables related to overall survival (OS). ResultsThe estimated 5-year OS was 36%. The rate of cervical lymph node (CLN) involvement was 28%. Patients with embryonic RMS who underwent chemotherapy enjoyed a favorable outcome according to the multivariate analysis (P = 0.047). Local recurrence (n = 30) and distant metastasis (n = 17) were the main causes of treatment failure. The rate of local recurrence or distant metastasis in the patients who underwent chemotherapy also decreased. Positive surgical margin (32%) was frequently seen in the AHNRMS. Primary site (P = 0.01), tumor size (P < 0.0001), CLN (P = 0.003), and margin status (P = 0.0002) were significant prognostic factors related to OS. ConclusionsHead and neck RMS in adults is a rare malignancy with a poor outcome, which is more likely to have CLN involvement compared with other soft tissue sarcomas of the head and neck. Standard treatment for AHNRMS should comprise surgery and chemotherapy.

N‐Glycolyl GM3 ganglioside immunoexpression in oral mucosal melanomas of Chinese

OBJECTIVE The aim of this study was to determine the expression of N-Glycolyl GM3 (NeuGcGM3) ganglioside in oral mucosal melanomas. MATERIALS AND METHODS To assess the presence of cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) mRNA, an RT-PCR assay was performed in melanoma cell line (ME), an oral mucosal ME, and two fresh oral mucosal melanoma tissues. Expression of NeuGcGM3 ganglioside was evaluated by immunohistochemistry in 44 primary oral mucosal melanomas and 10 oral melanotic nevi. Also, the expression of NeuGcGM3 was examined in ME by immunocytochemistry. RESULTS We first checked the expression of CMAH in ME and two fresh oral mucosal melanoma tissues. Presence of NeuGcGM3 ganglioside was evident in 37 of 44 cases (84.1%), showing a diffuse cytoplasmic and membranous staining. Patients with primary occurrence showed high levels of NeuGcGM3 ganglioside compared to patients with secondary occurrence. On the other hand, negative immunoreaction was evidenced in oral melanotic nevi. ME also presented the expression of NeuGcGM3 by immunocytochemistry. CONCLUSIONS In this work, we for the first time evaluated the expression of 14F7 MAb immunorecognition in oral mucosal melanomas. Our results were in agreement with the assumption that NeuGcGM3 ganglioside may be considered as target for passive and active immunotherapy in oral mucosal melanomas expressing this molecule and indicate less risk of recurrence and a better prognosis. Moreover, ME provides a platform for more studies on the specific function of NeuGcGM3 in oral mucosal melanomas.

TERT promoter mutation is absent in oral mucosal melanoma

http://dx.doi.org/10.1016/j.oraloncology.2015.05.009 1368-8375/ 2015 Elsevier Ltd. All rights reserved. Dear Editor Maintenance of telomeres is an essential step for malignant tumor formation. Telomerase is a ribonucleoprotein polymerase that maintains telomere ends by addition of the telomere repeat TTAGGG, and over 90% of human cancers show an up-regulation of the enzyme. Telomerase reverse transcriptase (TERT), which encodes the catalytic subunit of telomerase, is a determinant of telomerase activity. Recently two recurrent point mutations in TERT promoter region (C228T and C250T) have been shown to occur in a wide range of cancers. These mutations create de novo binding sites for ETS transcription factors that stimulate TERT transcription and enhance telomerase activity [1]. According to previous study TERT promoter mutations were found in 53% of cutaneous melanoma. Oral mucosal melanoma (OMM) is extremely rare and harbor different genetic alterations compared to cutaneous melanoma. It is currently unclear whether TERT promoter mutations also occur in OMM. To address this issue, we sequenced the TERT promoter region in primary tumors derived from 39 OMM. The patients’ clinical characteristics are listed in Table 1. We extracted genomic DNA from frozen OMM samples, and TERT promoter region were PCRamplified with previous reported primers (forward: 50-ACGAA CGTGGCCAGCGGCAG-30; reverse: 50-CTGGCGTCCCTGCACCCTGG30) [2]. Sanger sequencing were then performed and analyzed. Finally, we found that none of 39 OMM were positive for the TERT promoter C228T or C250T mutation. TERT encodes a rate-limiting catalytic subunit of telomerase, whose over-expression is associated with cancer cells’ immortality. The newly described TERT promoter mutations in human cancer provide new insight into the possible cause of increased TERT expression. Previous published works have found that TERT promoter mutations occurs frequently in bladder cancer, melanoma, hepatocellular carcinoma, etc., while is uncommon in esophageal cancer, lung cancer, prostate cancer, etc. [3]. In melanoma, TERT promoter mutations were found in 53% of cutaneous melanoma but was absent in uveal melanoma [4,5]. Our result showed OMM also lacked these mutations. It is unclear what causes such differential mutation incidences among different types of cancers. Some authors assumed that the TERT promoter mutations mainly occurred in tumors that are derived from tissues with low rates of self-renewal. In summary, we found for the first time that TERT promoter mutations were absent in OMM. This suggests that somatic mutation of TERT promoter play a limited role in OMM development and progression. Yours sincerely

Predictive value of pAKT/PTEN expression in oral squamous cell carcinoma treated with cetuximab-based chemotherapy.

OBJECTIVE Molecular alterations in downstream effectors of epidermal growth factor receptor may confer resistance to epidermal growth factor receptor inhibitors. Our aim is to investigate whether PTEN/pAKT expression predicts response to cetuximab-based chemotherapy in oral squamous cell carcinoma. STUDY DESIGN We analyzed a cohort of 50 patients with oral squamous cell carcinoma treated with cetuximab-based induction chemotherapy. PTEN expression and pAKT expression were assessed by immunohistochemistry and their correlation with treatment outcome was analyzed. RESULTS Of the study patients, 18.4% had low PTEN expression, and 38.8% had high pAKT expression. Lower pAKT expression were associated with pathologic remission (P = .034) and better disease-free survival (P = .031). CONCLUSION Our study demonstrates that pAKT expression is a predictive biomarker of cetuximab-based induction chemotherapy in OSCC.

Establishment and characterization of a rabbit oral squamous cell carcinoma cell line as a model for in vivo studies

The incidence of oral squamous cell carcinoma (SCC) is increasing but the long-term survival rate remains low. An animal model would therefore be helpful for evaluation of new treatment modalities for oral SCC. Hamster is small animal, therefore, the cancer of hamster cheek pouch is not optimal for tumor imaging. The VX2 cell line has been used in many carcinoma-related studies, including oral SCC research, but it is derived from cutaneous tissue and not mucosa. We chemically induced tongue squamous cell carcinoma in rabbits and subsequently established a rabbit squamous cell line. The cells grew in multiple layers without contact inhibition for 60 passages over 2 years and were positive for cytokeratin (CK). Electron microscopy revealed that cells were polygonal with rich microvilli on the surface, and there were desmosomes between cells and bundles of tonofibril beside the cell membrane. The chromosome number ranged from 71 to 272, with a modal value of 145 (12.4%). The cells were transplantable into nude mice subcutaneously or rabbit submucosally and produced carcinomas in all the animals. The cell line should be a useful tool for the study of the biological characteristics of oral SCC, especially tongue SCC.