Nomograms for Predicting Cancer-Specific Survival of Patients with Gingiva Squamous Cell Carcinoma: A Population-Based Study.

OBJECTIVE: The use of the traditional American Joint Committee on Cancer (AJCC) staging system alone has limitations in predicting the survival of gingiva squamous cell carcinoma (GSCC) patients. We aimed to establish a comprehensive prognostic nomogram with a prognostic value similar to the AJCC system. METHODS: Patients were identified from SEER database. Variables were selected by a backward stepwise selection method in a Cox regression model. A nomogram was used to predict cancer-specific survival rates for 3, 5 and 10 years in patients with GSCC. Several basic features of model validation were used to evaluate the performance of the survival model: consistency index (C-index), receiver operating characteristic (ROC) curve, calibration chart, net weight classification improvement (NRI), comprehensive discriminant improvement (IDI) and decision curve analysis (DCA). RESULTS: Multivariate analyses revealed that age, race, marital status, insurance, AJCC stage, pathology grade and surgery were risk factors for survival. In particular, the C-index, the area under the ROC curve (AUC) and the calibration plots showed good performance of the nomogram. Compared to the AJCC system, NRI and IDI showed that the nomogram has improved performance. Finally, the nomogram's 3-year and 5-year and 10-year DCA curves yield net benefits higher than traditional AJCC, whether training set or a validation set. CONCLUSION: We developed and validated the first GSCC prognosis nomogram, which has a better prognostic value than the separate AJCC staging system. Overall, the nomogram of this study is a valuable tool for clinical practice to consult patients and understand their risk for the next 3, 5 and 10 years.

Challenging management of gingival squamous cell carcinoma: a 10 years single-center retrospective study on Northern-Italian patients

BACKGROUND: Aim of this study was to describe the outcome of patients with gingival squamous cell carcinoma (GSCC), and to recognize aspects affecting clinical course and to consider survival rate. MATERIAL AND METHODS: The case records of patients, over a 10-year period, were retrospectively examined. Differences in distribution of the potential risk factors by prognosis were investigated through non-parametrical tests (Wilcoxon Rank-Sum and Fisher's Exact). Survival curves for age, therapy and stage were built by the Kaplan-Meier method and compared with Log-Rank test. RESULTS: 79 patients were analysed. Significant increase in mortality for patients older than 77 and for those with advanced stages was found. Cumulative survival rate 5 years after the diagnosis was 43%, while at 10 years was of 11%. CONCLUSIONS: With a statistical relationship between age and tumour stage with survival rates, and 70% of GSCC cases identified as stage IV, early GSCC diagnosis remains challenging

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Impact of superselective intra-arterial and systemic chemoradiotherapy for gingival carcinoma; analysis of treatment outcomes and prognostic factors.

BACKGROUND: We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC). METHODS: We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n = 66; SCRT group: n = 18). RESULTS: The median follow-up time was 24 (range: 1-124) months. The median prescribed dose was 60 (6-70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8, 95% confidence interval [CI]: 66.0-87.6; SCRT: 50.4, 95% CI: 27.6-73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6, 95% CI: 62.7-85.2; SCRT: 42.0, 95% CI: 17.7-70.9; P = 0.028) and local control rates (LC; IACRT: 77.2, 95% CI: 64.2-86.4; SCRT: 42.0, 95% CI: 17.7-70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups. CONCLUSIONS: This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.

Nomogram forecasting 3-, 5-, and 8-year overall survival and cancer-specific survival of gingival squamous cell carcinoma.

No nomogram models addressing the personalized prognosis evaluation of patients with gingival squamous cell carcinoma (GSCC) have been documented. We sought to establish nomograms to forecast overall survival (OS) and cancer-specific survival (CSS) of patients with GSCC. We collected the detailed clinicopathological information of 2505 patients with GSCC from the Surveillance, Epidemiology and End Results (SEER) program. Afterward, we divided the 2505 cases into a modeling group (n = 1253) and an external validation cohort (n = 1252) via random split-sample method. We developed the nomograms on the basis of the Kaplan-Meier and multivariate Cox survival analysis of the modeling group and then split the modeling cohort into two parts based on cut-off values: high- and low-risk cohorts. An improved survival was shown in the low-risk group compared to their counterpart, with a significant difference after the log-rank test. The performance of the nomograms was evaluated via concordance-index (C-index), the area under the receiver operating characteristic curve (AUC), and calibration curves. All the C-indexes and AUCs were greater than 0.7, showing high accuracy. Moreover, the calibrations showed that the actual observations were close to the 45° perfect reference line. In conclusion, we successfully developed two nomograms to provide individualized, patient-specific estimates of OS and CSS available for risk-stratification.

Elective neck dissection (END) and cN0 hard palate and upper gingival cancers: A National Cancer Database analysis of factors predictive of END and impact on survival.

BACKGROUND AND OBJECTIVES: The reported risk of nodal metastasis in hard palate and upper gingival squamous cell carcinoma (SCC) has been inconsistent with inadequate consensus regarding the utility of neck dissection in the clinically negative (cN0) neck. MATERIALS AND METHODS: Using the National Cancer Database, cN0 patients diagnosed with SCC of the head and neck with the subsites of the hard palate and upper gingiva were identified from 2004 to 2014. RESULTS: A total of 1830 patients were identified, and END was performed on 422 patients with cN0 tumors. Pathologically positive nodes occurred in 14% (59/422) of patients in this cohort. Higher tumor stage, academic hospital type, and large hospital volume (>28 cancer-specific cases/year) were associated with a higher likelihood of END both in univariate and multivariate analyses (P < .05). Patients >80 years of age were less likely to receive END on multivariate analysis (OR 0.52, 0.32-0.84). No variables, including advanced T stage, predicted occult metastases. Cox proportional hazards regression analysis showed that patients who underwent END demonstrated improved OS over an 11-year period (hazard ratio 0.75, P = .002). On subgroup analysis, this improvement was significant in patients with both stage T1 and T4 tumors. CONCLUSIONS: Tumor stage, hospital type, and hospital volume were associated with higher rates of END for patients with cN0 hard palate SCC and after controlling for clinical factors, END was associated with improved overall survival.

Gingival metastasis from primary hepatocellular carcinoma: a case report and literature review of 30 cases.

BACKGROUND: Gingival metastasis from primary hepatocellular cancer (HCC) is rare, highly malignant, and generally has no distinct symptoms. Not performing a biopsy can lead to misdiagnosis. This article reports an 87-year-old male with gingival metastasis from HCC. To gain a better insight into this disease, we also conducted a literature review of 30 cases and discussed the clinical and pathological characteristics, diagnosis, treatment and prognosis of this unusual form of liver cancer. CASE PRESENTATION: An 87-year-old man was hospitalized with a chief complaint of chronic constipation and diffuse lower extremity edema. His past medical history included a three-year hepatitis B infection and a cerebral infarction 17 years prior. Imaging examination detected a massive hepatocellular carcinoma in the right liver lobe and multiple metastases in the lungs. Oral examinations revealed a reddish, cherry-sized exophytic mass on the right upper gum. The mass was tentatively diagnosed as a primary gingival tumor and was ultimately confirmed by biopsy as a metastatic carcinoma originating in the liver. The patient decided, with his guardians, to receive palliative care and not to remove the mass. Unfortunately, the patient accidentally bit the mass open; profuse bleeding ensued and local pressure exerted a poor hemostatic effect. The patient's condition worsened, and he eventually died of multiple organ failure. We also performed a literature review and discussed 30 cases of gingival metastases from HCC. The findings indicated that these lesions affected males more than females, with a ratio of 6:1, and infiltrated the upper gingivae (63.1%) more than the lower gingivae (36.7%). Survival analysis indicated that the overall survival for patients with upper gingival metastasis was worse than for those with lower gingival metastasis, and patients receiving treatments for primary liver cancer or metastatic gingival tumors had better overall or truncated survival times. CONCLUSION: Gingival metastasis from primary hepatocellular carcinoma is rare, and its diagnosis has presented challenges to clinicians. To avoid a potential misdiagnosis, a biopsy is mandatory regardless of whether a primary cancer is located. Early diagnosis and treatment for primary liver cancer or metastatic gingival lesions may improve survival expectations.

Oncologic outcome of marginal mandibulectomy in squamous cell carcinoma of the lower gingiva.

BACKGROUND: There is a large amount of controversy about the best management of the mandible in oral squamous cell carcinoma (SCC), mainly owing to the inability to acquire accurate bone invasion status. Therefore, our goal was to analyse the oncologic safety in patients undergoing marginal mandibulectomy (MM) for cT1-2 N0 SCC of the lower gingiva. METHODS: Patients undergoing MM for untreated cT1-2 N0 SCC of the lower gingiva were retrospectively enrolled. The main endpoints of interest were locoregional control (LRC) and disease-specific survival (DSS). RESULTS: A total of 142 patients were included in the analysis, and a pathologic positive node was noted in 27 patients. Cortical invasion was reported in 23 patients, and medullary invasion was reported in 9 patients. The 5-year LRC and DSS rates were 85 and 88%, respectively. Patients with bone invasion had a significantly higher risk for recurrence than patients without bone invasion. However, the DSS was similar in patients with versus without bone invasion. Patients with a high neutrophil lymphocyte ratio had a higher risk for worse prognosis. CONCLUSIONS: The oncologic outcome in patients undergoing MM for cT1-2 N0 SCC of the lower gingiva was favourable; bone invasion was not uncommon, but it significantly decreased the prognosis in patients undergoing MM.

Definitive radiotherapy vs. postoperative radiotherapy for lower gingival carcinomas of the mandible : A single-center report about outcome and toxicity.

PURPOSE: To assess radiotherapy (RT) outcomes in patients with gingival carcinoma and growth up to or involvement of the lower jaw bone. METHODS: This was a retrospective analysis of 51 patients with squamous cell carcinomas of the gingiva. Patients received definitive (group 1, 31.4%) or postoperative (group 2, 66.7%) RT between 2005 and 2017 at the Department of Radiation Oncology, University Hospital Heidelberg. The primary endpoint was overall survival (OS) in both treatment groups. Other endpoints were local-disease-free survival (LDFS), progression-free survival (PFS) and treatment-related toxicity (Common Terminology Criteria for Adverse Events, CTCAE, Version 4.03). RESULTS: Median age at first diagnosis was 63 years. All patients had a local advanced disease (American Joint Commission on Cancer [AJCC] stage III-IV). After a median follow-up of 22 months (range 3-145 months), 20 patients (39.2%) were still alive. At 5 years, OS rate was 36.6%. No significant differences in OS (p = 0.773), PFS (p = 0.350) and LDFS (p = 0.399) were observed between the two groups. Most common higher-grade acute RT-related complications (≥ grade 3) were dermatitis (78.2%), oral mucositis (61.7%), xerostomia (51.5%), and loss of taste (74.6%). Three cases (5.8%) of osteoradionecrosis (ORN) of the lower jaw were detected after 15-31 months. CONCLUSIONS: Definitive and postoperative RT have similar treatment outcomes for patients with lower gingiva carcinomas of the lower jaw. The most common acute complications (grade ≥3) were dermatitis, oral mucositis, xerostomia and loss of taste.

Prognostic factors and treatment outcomes of advanced maxillary gingival squamous cell carcinoma treated by intra-arterial infusion chemotherapy concurrent with radiotherapy.

BACKGROUND: The aim of this study was to evaluate the prognostic factors and treatment outcomes of advanced maxillary gingival squamous cell carcinoma (SCC) treated with intra-arterial infusion chemotherapy concurrent with radiotherapy. METHODS: A total of 46 patients were reviewed retrospectively in this study. The treatment schedule comprised intra-arterial chemotherapy (total, 60 mg/m2 docetaxel and 150 mg/m2 cisplatin) and three-dimensional computed tomography based, daily conventional radiotherapy (total, 60 Gy/30 fr) for 6 weeks. RESULTS: The median follow-up period was 40 months (range, 3-110 months). The 3-year overall survival and locoregional control rates for all patients were 64.3% and 84.3%, respectively. The OS rate of the patients with N0-1 was significantly higher than that of the patients with N ≥ 2 (P < .05). No grade 5 toxicities were observed. CONCLUSIONS: Intra-arterial infusion chemotherapy concurrent with radiotherapy was effective for advanced maxillary gingival SCC.

Survival Outcomes in T4aN0M0 Mandibular Gingival Squamous Cell Carcinoma Treated with Surgery Alone.

OBJECTIVES: To measure disease-free, disease-specific, and overall survival among patients with T4aN0M0 mandibular gingival squamous cell carcinoma who were treated with surgery alone. STUDY DESIGN: Case series with chart review. SETTING: Tertiary care center. SUBJECTS AND METHODS: A retrospective chart review was performed of all adult patients treated surgically with an oral cavity composite resection between January 2005 and March 2017. Among other data, patient preoperative characteristics were recorded (eg, age, sex, smoking history, alcohol use, and clinical stage); operative notes were reviewed to determine tumor subsite involvement, reconstruction method, and intraoperative surgical complications; and pathology reports were evaluated for various pathologic findings. Survival outcomes were determined with Kaplan-Meier analysis. RESULTS: The mean follow-up was 18.5 months (range, 0.1-100). The 1- and 5-year disease-free survival rates were 90.5% and 84.5%, respectively, while the 1- and 5-year disease-specific survival rates were 87.8% and 81.9%. The 1- and 5-year overall survival rates were 86.4% and 80.6%. CONCLUSIONS: Patients with T4aN0M0 squamous cell carcinoma of the mandibular gingiva treated with surgery alone have a 5-year overall survival of 80.6%. Treatment with surgery alone obviates morbidities associated with adjuvant therapy while upholding survival outcomes.

The pattern of failure and predictors of locoregional control in lateralized buccogingival cancer after postoperative radiation therapy.

BACKGROUND: To evaluate the failure pattern and identify predictors of locoregional control in lateralized buccogingival cancer after postoperative radiotherapy (RT) at a single institution. METHODS: We retrospectively reviewed the clinical data of 150 patients with lateralized oral squamous cell carcinoma, including carcinoma of the buccal mucosa, gingiva and retromolar trigone. All patients underwent radical surgery followed by postoperative RT with or without concurrent chemotherapy. We registered planning computer tomography images with images obtained at recurrence and categorized the failure pattern as in-field, marginal, or out-field recurrence. RESULTS: The median follow-up duration was 47 months (range, 2-131 months). Twenty-eight patients (19%) experienced locoregional failure, including 20 local failure, 5 regional failure and 3 with both. Among the 24 patients who had image studies at recurrence, 15 patients had in-field recurrence, 5 were marginal recurrence and 4 were out-field recurrence. Seven patients (5%) had contralateral neck failure. Four of 5 patients with marginal failure had recurrent tumors in the infratemporal fossa. In multivariate analysis, extracapsular spread and positive or close surgical margin were associated with poor locoregional control. CONCLUSION: Local in-field recurrence is the most common failure pattern in lateralized buccogingival cancer after postoperative RT. The infratemporal fossa is a risk area for marginal failure and should be encompassed adequately in the postoperative RT field. Extracapsular spread and positive or close margin are predictors of locoregional control for lateralized oral cancer. Patients exhibiting such adverse features require more aggressive treatment.

Galectin-1 expression is associated with tumour immunity and prognosis in gingival squamous cell carcinoma.

AIMS: Galectin-1 (Gal-1) is a ß-galactoside-binding protein that overexpresses in cancer and plays pivotal roles in tumour progression. Gal-1 regulates angiogenesis and invasiveness, and suppresses tumour immunity by inducing T cell apoptosis. Several studies have examined the relationship between Gal-1 and tumour immunosuppression in vivo, but they have not examined the clinicopathological relationship between Gal-1 expression and apoptotic T cell number in human tissue. In this study, we investigated the association between Gal-1 expression and apoptotic T cells of gingival squamous cell carcinoma (GSCC), as well as other clinicopathological factors. METHODS: Immunohistochemical investigation of 80 GSCC specimens using anti-Gal-1, anti-CD3, anti-CD4, anti-CD8, anti-CD34, antipodoplanin and anticleaved caspase-3 (CC-3) antibodies was performed. Relative expression levels of CD3 and CC-3, as well as CD8 and CC-3 were assessed simultaneously by double immunostaining. Gal-1 expression and T cell apoptosis were evaluated in 6 high-power fields (3 in the tumour and 3 in the stroma). RESULTS: Gal-1 expression in GSCC was significantly correlated with T cell infiltration (p=0.036), and apoptosis of CD3+ and CD8+ T cells (p<0.001). Moreover, Gal-1 expression was significantly correlated with lymph node metastasis (p=0.021), histological differentiation (p<0.001) and overall survival rate (p=0.021). CONCLUSIONS: These findings suggest that Gal-1 plays an important role in immune escape of GSCC cells, and Gal-1 expression level may be a useful clinicopathological prognostic marker for GSCC.

Prognostic and staging implications of mandibular canal invasion in lower gingival squamous cell carcinoma.

A multi-institutional study was undertaken to determine whether mandibular canal (MC) invasion and mandibular medullary bone invasion are independent factors in lower gingival squamous cell carcinoma (SCC). A total of 345 patients with lower gingival SCC were retrospectively reviewed. Mandibular bone invasion was categorized into three types; no bone invasion; invasion through cortical bone (medullary); and MC invasion. The overall survival rate and factors affecting local, regional, and distant failures were assessed by Cox proportional hazards regression analysis and Kaplan-Meier estimates. Bone invasion was present in 201 (58%) patients, of whom 107 (31%) had medullary invasion and 94 (27%) had MC invasion. Using the International Union Against Cancer (UICC) staging system and American Joint Committee on Cancer (AJCC) system, 171 (50%) patients were classified as T4a. When the bone invasion criteria were excluded from the UICC/AJCC system definition, 152 T4a tumors were downstaged and reclassified to T1 in 12 (3%), to T2 in 98 (28%), and to T3 in 42 (12%). In Cox multivariate analysis, MC invasion was an independent predictor of overall survival but medullary bone invasion was not. Medullary bone invasion was an independent variable for distant control. The current T staging system has restricted prognostic utility. The authors recommend a modified T staging system, whereby tumors with MC invasion instead of medullary bone invasion are classified as T4a, and tumors are first classified as T1 to T3 based on size and then upstaged by one T classification in the presence of medullary invasion.

Clinical implications of recent exodontia before diagnosis of gingival squamous cell carcinoma: A new classification.

BACKGROUND: The purpose of this study was to clarify the clinical implications of cases with recent dental extractions to establish a new classification of gingival squamous cell carcinoma (SCC). METHODS: A total of 156 patients were enrolled in this study. The subjects were divided into 3 groups: type I (dentate; n = 46), type II (edentulous; n = 55), and type III (dental extraction; n = 55). Continuous clinical and treatment variables were analyzed by 1-way analysis of variance (ANOVA) or t test, and categorical variables were evaluated by chi-square tests. Assessment of 5-year survival rates were carried out by the Kaplan-Meier analysis, and the influence of related factors was evaluated by the log-rank test. RESULT: The 55 type III patients showed a high probability of bony invasion (80%) and a lower 5-year survival rate (48%) than the other 2 groups. CONCLUSION: Our proposed classification may help clinicians to identify patients with gingival SCC who present with more advanced disease status.

High interstitial fluid pressure promotes tumor progression through inducing lymphatic metastasis-related protein expressions in oral squamous cell carcinoma.

OBJECTIVE: The present study was carried out to analyze the interstitial fluid pressure (IFP) values in patients with oral squamous cell carcinoma and identify the relationship between the IFP and tumor prognosis. METHODS: We investigated tumor lymphatic metastasis-related protein (VEGFC, VEGFD and VEGFR3) expressions change on SCC-4 and SCC-9 cells subjected to increased extracellular pressure in vitro and analyzed the relationship between these proteins and IFP, and prognosis of patients with oral squamous cell carcinoma. RESULTS: The results showed that the elevated extracellular pressure significantly resulted in a dramatic increase of VEGFC, VEGFD and VEGFR3 protein expressions in OSCC. More important, the activation of VEGFC, VEGFD and VEGFR3 proteins through IFP elevation contributed to poor prognosis for patients with OSCC. CONCLUSIONS: These results suggest an important potential clinical application of measuring IFP, which can be used as a generic marker of prognosis evaluation and response to therapy. Furthermore, VEGFC, VEGFD and VEGFR3 may be useful targets in developing novel and specific therapeutic tool for OSCC patients with high IFP.

Radiation therapy with concurrent retrograde superselective intra-arterial chemotherapy for gingival carcinoma.

PURPOSE: The aim of this study was to review the efficacy and toxicity of radiation therapy with concurrent retrograde superselective intra-arterial chemotherapy in the treatment of gingival carcinoma. METHODS AND MATERIALS: In all, 34 patients (21 men and 13 women) with squamous cell carcinoma of the gingiva underwent radiation therapy with concurrent retrograde superselective intra-arterial chemotherapy. Treatment consisted of daily external irradiation and concurrent retrograde superselective intra-arterial infusion with cisplatin and docetaxel. A median total dose of 60 Gy in 30 fractions was delivered to tumors. RESULTS: Of the 34 patients, 29 (85 %) achieved a complete response (CR) and 5 had residual tumors. Of the 29 patients with a CR, 2 had local recurrences and 1 had distant metastasis 1-15 months after treatment. Twenty-six of the 36 patients had survived at a median follow-up time of 36 months (range 12-79 months); 4 died of cancer and 4 died of non-cancer-related causes. At both 3 and 5 years after treatment, the overall survival rates were 79 % and the cause-specific survival rates were 85 %. Osteoradionecrosis of the mandibular bone only developed in 1 patient after treatment. CONCLUSION: Radiation therapy with concurrent retrograde superselective intra-arterial chemotherapy was effective and safe in the treatment of gingival carcinoma. This treatment may be a promising curative and organ-preserving treatment option for gingival carcinoma.

Prognosis for gingival carcinomas with a delayed diagnosis after dental extraction.

PURPOSE: In gingival squamous cell carcinoma (GSCC), the association between survival and previous dental extraction (DE) is controversial. The purpose of this study was to investigate the prognosis for patients in whom GSCC was detected after DE was performed. PATIENTS AND METHODS: DE for GSCC tumor symptoms was performed in 19 patients before diagnosis (DE group) and not in 58 patients (non-DE group). The clinical features, characteristics, and prognosis were evaluated statistically between the 2 groups. RESULTS: The interval from DE to the first hospital visit was 1.1 to 97 weeks (median, 7.3 weeks). There was no significant difference in tumor status, node status, local recurrence, pathologically positive lymph nodes, or distant metastasis between the DE and non-DE groups. Bone invasion was observed radiographically in 6 patients with mandibular GSCC in the DE group (100%) and 13 in the non-DE group (68.4%). There was a significant difference in bone invasion between the DE and non-DE groups (P < .01). Segmental mandibulectomy was performed in 11 patients (84.6%) in the DE group and 21 patients (61.8%) in the non-DE group. Extent of resection tended to be larger for the DE group. The 5-year overall survival rate was 84.6% for the DE group and 65.8% for patients with mandibular GSCC in the non-DE group. For maxillary GSCC, the survival rates differed significantly between groups (33.3% in DE group and 73.7% in non-DE group). CONCLUSIONS: For mandibular GSCC, the resection field was appropriate for the extent of bone invasion after DE and the prognosis was similar to that in the non-DE group. For maxillary GSCC, a broad surgical field is suggested because of the potential for rapid spread in cancellous bony trabeculae.

Genome-wide expression and copy number analysis identifies driver genes in gingivobuccal cancers.

The molecular mechanisms contributing to the development and progression of gingivobuccal complex (GBC) cancers-a sub-site of oral cancer, comprising the buccal mucosa, the gingivobuccal sulcus, the lower gingival region, and the retromolar trigone-remain poorly understood. Identifying the GBC cancer-related gene expression signature and the driver genes residing on the altered chromosomal regions is critical for understanding the molecular basis of its pathogenesis. Genome-wide expression profiling of 27 GBC cancers with known chromosomal alterations was performed to reveal differentially expressed genes. Putative driver genes were identified by integrating copy number and gene expression data. A total of 315 genes were found differentially expressed (P ≤ 0.05, logFC > 2.0) of which 11 genes were validated by real-time quantitative reverse transcriptase-PCR (qRT-PCR) in tumors (n = 57) and normal GBC tissues (n = 18). Overexpression of LY6K, in chromosome band 8q24.3, was validated by immunohistochemical (IHC) analysis. We found that 78.5% (2,417/3,079) of the genes located in regions of recurrent chromosomal alterations show copy number dependent expression indicating that copy number alteration has a direct effect on global gene expression. The integrative analysis revealed BIRC3 in 11q22.2 as a candidate driver gene associated with poor clinical outcome. Our study identified previously unreported differentially expressed genes in a homogeneous subtype of oral cancer and the candidate driver genes that may contribute to the development and progression of the disease. © 2011 Wiley Periodicals, Inc.

Prognosis of gingival squamous cell carcinoma diagnosed after invasive procedures.

Gingival squamous cell carcinoma (SCC) has a relatively poor prognosis, because differential diagnoses of periodontitis and osteomyelitis are difficult to exclude. As such, gingival SCC is usually diagnosed late, following invasive procedures such as extraction or curettage. The purpose of this study was to classify gingival SCC patients into two groups according to the location of their primary lesion: dentate and edentulous, and to determine the appropriate treatment strategy by comparing clinical and histological features as well as treatment results. The medical records of 76 patients diagnosed with gingival SCC and treated at one institute from 1 January 1993 to 31 December 2007 were reviewed. The overall 5-year survival rate was 60.7%, and the mean survival was 98 months. Factors affecting survival included bone invasion of the primary lesion (p = 0.035), neck node metastasis (p = 0.001), and local recurrence (p = 0.000). The results suggest that more aggressive treatment, such as setting a broad surgical field and enforcing preventive neck dissection, can improve outcome, although they are associated with increased rate of cancer bone invasion and neck metastasis in patients diagnosed with cancer after receiving invasive procedures.