Yunteng Wu

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.

Malignant peripheral nerve sheath tumours in the head and neck region: retrospective analysis of clinicopathological features and treatment outcomes

Malignant peripheral nerve sheath tumours (MPNST) are rare soft tissue sarcomas. The aim of this study was to assess clinicopathological characteristics and prognostic factors in order to improve the treatment of such tumours in the head and neck region. We performed a retrospective analysis of head and neck MPNST patients in our hospital between 1996 and 2012. Clinical features and pathological findings of these cases (n=43) were summarized. In addition, prognostic variables were evaluated by univariate and multivariate analyses. The median age of the patients at presentation was 41 years. Surgery was the main treatment approach. Pertinent information regarding the presence of neurofibromatosis type 1 was found in 13 patients (30.2%). Two-thirds of these patients were admitted for a primary tumour (n=27, 62.8%), while one-third (n=16, 37.2%) were treated for recurrent neoplasms. The overall survival rate was 46.5%. Multivariable analysis identified tumour size, surgical margins, and postoperative radiotherapy to be independent prognostic factors. MPNST of the head and neck is extremely difficult to manage. Surgery with postoperative radiation may be the optimum choice of treatment for primary head and neck MPNST.

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.

Loss of nuclear BAP1 expression is associated with poor prognosis in oral mucosal melanoma

Oral mucosal melanoma (OMM) is an aggressive neoplasm with an extremely poor prognosis. BAP1 is a tumor suppressor that has been associated with the outcome of melanomas and other malignancies. In this study, we investigated the genetic alterations in BAP1 and the prognostic potential of BAP1 protein expression in oral mucosal melanoma. DNA sequence analysis of BAP1 from 12 OMM patient samples revealed missense mutations in the tissues from four patients. Based on immunohistochemical staining, loss of nuclear BAP1 expression was associated with poor overall survival (P < 0.001, Log-rank = 21.308) and distant metastasis (P = 0.034, OR = 0.320). Multivariate analysis showed BAP1 to be an independent prognostic factor (P = 0.027, HR = 0.479). It thus appears that loss of nuclear BAP1 expression is an independent prognostic factor of poor overall survival and associated with distant metastasis in OMM.

Ki67 Proliferation Index as a Histopathological Predictive and Prognostic Parameter of Oral Mucosal Melanoma in Patients without Distant Metastases

Background: To investigate the relationship between clinical and histopathological characteristics and overall survival of patients with oral mucosal melanoma (OMM) without distal metastasis in order to provide predictive prognostic information of OMM. Methods: Ki67 expression was assessed by immunohistochemistry in 123 patients with OMM without distant metastases. The associations between Ki67 expression and clinical features and overall survival (OS) of patients were statistically analyzed. The Ki67 levels of the primary and recurrent lesions from 14 OMM patients were compared. Results: Univariate analysis showed that tumor type and cervical lymph node (CLN) status, as well as Ki67 expression, were all correlated with survival. Cox proportional hazards regression analysis identified Ki67 expression and CLN status as independent prognostic factors in OMM patients. Further, we found that Ki67 expression was associated with clinical tumor type of OMM. Moreover, with a cut-off point of 20%, patients with lower Ki67 scores showed a survival advantage over those with higher Ki67 scores. Conclusions: Ki67 expression may be a useful pathological predictor of survival of OMM patients without distant metastases.

The clinical significance of c-Kit mutations in metastatic oral mucosal melanoma in China

c-Kit mutations are frequently detected in mucosal melanomas, but their clinical significance in metastatic oral mucosal melanomas (OMM) remains unclear. The main purpose of this study was to investigate the clinical and pathological features of metastatic OMMs with c-Kit mutations and the efficiency of the tyrosine kinase inhibitor imatinib in treating metastatic OMMs. We found thatresidual primary lesion and neck lymph nodes could act as independent prognostic factors in metastatic OMM patients. c-Kit mutations were detected in 22 out of 139 (15.8%) metastatic OMM patients. Under chemotherapy, the overall survival (OS) of c-Kit mutant patients was significantly shorter than that of wild-type patients. The Ki67 expression was significantly higher in c-Kit mutant patients than in wild-type patients. In distant metastatic OMM patients with c-Kit mutations, the treatment with c-Kit inhibitor resulted in a better OS. In conclusion, residual primary lesion, cervical lymph nodes and c-Kit mutations act as adverse prognostic factors of metastatic OMMs. The Kit inhibitor imatinib could benefit metastatic OMM patients with c-Kit mutations.

Successful delivery derived from cryopreserved rare human spermatozoa with novel cryopiece

Herein, we report the clinical outcomes following intracytoplasmic sperm injection (ICSI) with cryopiece cryopreserved rare human spermatozoa from severe male factor infertility patients. We established a novel cryopiece system on the basis of previous studies. In this study, 126 spermatozoa from four patients with non‐obstructiveazoospermia (NOA) or severe oligozoospermia were stored in cryopiece and then thawed on the day of the oocyte retrieval, 88 (83%) spermatozoa were recovered with a 47.5% (38 of 80) motile rate. Routine ICSI were performed in enrolled 30 MII oocytes from their spouse with their own spermatozoa, respectively. Twenty‐two (73%) fertilization and 19 (86%) zygote cleavage were observed. Finally, a total of 11 embryos were achieved and each female patient received a transplantation of two fresh embryos. Four healthy babies were born at term. In conclusion, our novel cryopiece can be applied in assisted reproduction through ICSI with an effective motile spermatozoa recovery rate, high fertilization rate, and successful pregnancy result.