Early Tongue Squamous Cell Carcinoma Research Articles

The pattern and spread of invasion can predict late cervical lymph node metastasis in early tongue squamous cell carcinoma

To determine the predictive indexes of late cervical lymph node metastasis in early tongue squamous cell carcinoma (TSCC). We retrospectively analyzed the cases of 25 patients with stage I/II TSCC who had undergone surgical treatment without elective neck dissection. We evaluated the relationships between clinicopathologic factors and the occurrence of late cervical lymph node metastasis. Of the 25 cases, metastasis to the cervical lymph nodes was observed in nine cases (36.0%). The clinicopathological factors associated with late cervical lymph node metastasis were the mode of invasion (MOI, p = 0.032), depth of invasion (DOI, p = 0.004), and perineural invasion (PNI, p = 0.040). A multivariate analysis revealed that only the DOI was an independent predictor of late cervical lymph node metastasis. The combination of the DOI and MOI or the PNI and MOI was significantly correlated with late cervical lymph node metastasis (p = 0.004 and p = 0.012, respectively). Our findings suggest that combinations of the MOI, DOI, and PNI could be used as an index for predicting late cervical lymph node metastasis in early TSCC.

High-Frequency Intraoral Ultrasound for Preoperative Assessment of Depth of Invasion for Early Tongue Squamous Cell Carcinoma: Radiological-Pathological Correlations.

The eighth edition of the TNM classification officially introduced "depth of invasion" (DOI) as a criterion for determining the T stage in tongue squamous cell carcinoma. The DOI is a well-known independent risk factor for nodal metastases. In fact, several experts strongly suggest elective neck dissection for tongue cancer with a DOI > 4 mm due to the high risk of early and occult nodal metastases. Imaging plays a pivotal role in preoperative assessments of the DOI and, hence, in planning the surgical approach. Intraoral ultrasound (IOUS) has been proposed for early-stage SCC of the oral tongue as an alternative to magnetic resonance imaging (MRI) for local staging. The aim of this work is to investigate the accuracy of IOUS in the assessment of the DOI in early oral SCC (CIS, pT1, and pT2). A total of 41 patients with tongue SCCs (CIS-T2) underwent a preoperative high-frequency IOUS. An IOUS was performed using a small-size, high-frequency hockey-stick linear probe. The ultrasonographic DOI (usDOI) was retrospectively compared to the pathological DOI (pDOI) as the standard reference. In patients who underwent a preoperative MRI, their usDOI, magnetic resonance DOI (mriDOI), and pDOI were compared. Specificity and sensitivity for the IOUS to predict a pDOI > 4 mm and to differentiate invasive and noninvasive tumors were also evaluated. A high correlation was found between the pDOI and usDOI, pDOI and mriDOI, and usDOI and mriDOI (Spearman's ρ = 0.84, p < 0.0001, Spearman's ρ = 0.79, p < 0.0001, and Spearman's ρ = 0.91, p < 0.0001, respectively). A Bland-Altman plot showed a high agreement between the usDOI and pDOI, even though a mean systematic error was found between the usDOI and pDOI (0.7 mm), mriDOI and pDOI (1.6 mm), and usDOI and mriDOI (-0.7 mm). The IOUS was accurate at determining the T stage (p < 0.0001). The sensitivity and specificity for the IOUS to predict a pDOI ≥4 mm were 92.31% and 82.14%, respectively, with an AUC of 0.87 (p < 0.0001). The specificity, sensitivity, negative predictive value (NPV), and positive predictive value (PPV) for the IOUS to predict an invasive cancer were 100%, 94.7%, 60%, and 100%, respectively. The AUC was 0.8 (95% CI 0.646-0.908, p < 0.0001). The IOUS was accurate in a preoperative assessment of a pDOI and T stage, and can be proposed as an alternative to MRI in the preoperative staging of tongue SCC.

Subnetwork representation learning for discovering network biomarkers in predicting lymph node metastasis in early oral cancer

Cervical lymph node metastasis is the leading cause of poor prognosis in oral tongue squamous cell carcinoma and also occurs in the early stages. The current clinical diagnosis depends on a physical examination that is not enough to determine whether micrometastasis remains. The transcriptome profiling technique has shown great potential for predicting micrometastasis by capturing the dynamic activation state of genes. However, there are several technical challenges in using transcriptome data to model patient conditions: (1) An Insufficient number of samples compared to the number of genes, (2) Complex dependence between genes that govern the cancer phenotype, and (3) Heterogeneity between patients between cohorts that differ geographically and racially. We developed a computational framework to learn the subnetwork representation of the transcriptome to discover network biomarkers and determine the potential of metastasis in early oral tongue squamous cell carcinoma. Our method achieved high accuracy in predicting the potential of metastasis in two geographically and racially different groups of patients. The robustness of the model and the reproducibility of the discovered network biomarkers show great potential as a tool to diagnose lymph node metastasis in early oral cancer.

P-28 The potential of MET immunoreactivity for prediction of lymph node metastasis in early tongue squamous cell carcinoma

P-28 The potential of MET immunoreactivity for prediction of lymph node metastasis in early tongue squamous cell carcinoma

Development and validation of multiparametric MRI-based nomogram for predicting occult metastasis risk in early tongue squamous cell carcinoma

BackgroundNomograms are currently used in predicting individualized outcomes in clinical oncology of several cancers. However, nomograms for evaluating occult nodal metastasis of patients with squamous cell carcinoma of lateral tongue (SCCLT) have not been widely investigated for their functionality. This retrospective cohort study was designed to address this question.MethodsThis study was divided into primary and validation cohorts. The primary cohort comprised 120 patients diagnosed between 2012 and 2017, whereas the validation cohort included 41 patients diagnosed thereafter. The diagnostic value of multiparametric MRI, including radiologic tumor thickness threshold (rTTT) in three-dimensions, paralingual distance, and sublingual distance were investigated. A nomogram was developed based on stepwise logistic regression of potential predictors associated with nodal metastasis in the primary cohort and then tested for predictive accuracy in the validation cohort using area under the curve (AUC) and goodness-of-fit tests.ResultsMultivariate analysis, tumor size (odd ratio [OR] 15.175, 95% confidence interval [CI] 1.436–160.329, P = 0.024), rTTT (OR 11.528, 95% CI 2.483–53.530, P = 0.002), paralingual distance (OR 11.976, 95% CI 1.981–72.413, P = 0.005), and tumor location (OR 6.311, 95% CI 1.514–26.304, P = 0.011) were included in the nomogram to predict the likelihood of having cervical metastasis. A nomogram cutoff value of 210 points (sensitivity 93.8%, specificity 87.5%) was significantly different to classify the patients metastasis risk group (P < 0.001). Nomogram showed predictive accuracy with AUC 0.881 (95% CI 0.779–0.983, P < 0.001) and good calibration after the validation.ConclusionsA preoperative nomogram incorporating multiparametric MRI demonstrated good prediction and performed adequately in our study. Three-dimensional assessment of occult metastasis risk value obtained from this nomogram can assist in preoperative decision making for individual patients with early-stage SCCLT. The probability of nodal metastasis tended to be greater than 20% in patients with high metastasis risk or nomogram total score > 210 points.

The Pattern and Spread of Invasion Can Predict Late Cervical Lymph Node Metastasis in Early Tongue Squamous Cell Carcinoma

The Pattern and Spread of Invasion Can Predict Late Cervical Lymph Node Metastasis in Early Tongue Squamous Cell Carcinoma

1152P - Topographical distribution of sentinel lymph nodes in early tongue squamous cell carcinomas

BackgroundDespite advances in early detection, diagnosis, and treatment of oral squamous cell carcinoma (OSCC), the survival for patients with early stage remains at approximately 80% for the past 30 years. Regional lymph node metastasis is an important prognostic factor. Therefore, early detection of the cervical lymph nodes metastasis is expected to further improve survival. Sentinel lymph node biopsy (SLNB) is a widely accepted procedure in various human malignancies. In clinically N0 (cN0) early OSCC cases, SLNB has received considerable attention for its role in deciding whether to perform neck dissection. The objective in this study is to investigate the topographical distribution of sentinel lymph nodes (SLNs) and occult metastatic lymph nodes in early tongue squamous cell carcinoma (TSCC). MethodsA total of 64 patients with T1/2N0 TSCC underwent SLNB between 2001 and 2016. The location of SLNs was determined by radioisotope (RI) method with preoperative lymphoscintigraphy and intraoperative use of a handheld gamma probe, and evaluated by histopathological and genetic examinations. Patients with metastatic lymph nodes were treated with completion neck dissection. Excised lymph nodes were grouped into the neck level according to the international guidelines. ResultsSLNs were successfully identified with RI method (100%). The rate of SLN identified side was 84.5% in ipsilateral, 12.1% in bilateral, and 3.4% in contralateral. Nine of 64 patients (14.1%) had metastasis-positive SLN. Six patients with negative SLN developed the latent neck lymph node metastasis. There was no patients with metastatic involvement of neck level IV and V. The sensitivity, specificity, and accuracy was 60% (9/15), 100% (49/49), and 90.6% (58/64), respectively. ConclusionsSLNB is a minimally invasive and highly reliable method staging the cN0 for patients with early OSCC. Completion neck dissection of level I-III in SLNB-positive patients might be sufficient in patients with early TSCC. Our study showed that SLNB was helpful in clarifying unexpected bilateral or contralateral metastatic drainage patterns. SLNB provides more accurate staging than elective neck dissection or wait and see policy. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Surgical treatment of early tongue squamous cell carcinoma and patient survival.

Surgical options for treating early tongue squamous cell carcinoma and patient survival were explored. Clinical records of 128 patients with early tongue squamous cell carcinoma who were treated in Henan Province Hospital of TCM from June, 2010 to June, 2013 were retrospectively analyzed. According to adopted treatment plan, the patients were divided into 3 groups: 42 patients in surgical therapy alone group, 46 patients in preoperative radiotherapy group, and 40 patients in postoperative radiotherapy group. Statistical analysis was performed on the general data of patients and clinical records, as well as the 5-year survival rate and recurrence rate. The overall 5-year survival rate for all patients was 86.7% (111/128), and the 5-year disease-specific survival rate was 88.8% (111/125). In the individual groups, the 5-year survival rate and the 5-year disease-specific survival rate were 91.3% (84/92) and 91.3% (84/92), respectively, in the surgical therapy alone group 76.9% (10/13) and 83.3% (10/12), respectively, in the preoperative radiotherapy group, and 73.9% (17/23) and 81.0% (17/21), respectively, in the postoperative radiotherapy group. There were no statistically significant differences in 5-year survival rate (χ2=5.990, P=0.051) and 5-year disease-specific survival rate (χ2=2.223, P=0.329) among the three groups. In total, there were 25 cases of recurrence during follow-up. The recurrence rate was 19.5%; the local recurrence rate was 11.7% (15/128); and the regional recurrence rate was 7.8% (10/128). There were 6 cases of metastasis, and the metastatic rate was 4.7%. There were no statistically significant differences in recurrence rate and metastatic rate among the three groups. Compared with surgical therapy alone, radiotherapy combined with surgical therapy neither improved 5-year survival rate nor reduced recurrence rate. Therefore, surgical therapy alone is suggested to be the preferred option for treating early tongue squamous cell carcinoma.

Importance of tumor budding grade as independent prognostic factor for early tongue squamous cell carcinoma.

Factors involved in neck lymph node metastasis (NLM) and prognosis of early tongue squamous cell carcinoma (SCC) remain unknown. We analyzed disease-specific survival (DSS) and NLM including tumor budding grade (TBG) among 64 patients with cT1/2N0 tongue SCC. Univariate analysis of DSS of primary lesions uncovered significant differences in new cT, pT, new pT, pDiameter, venous infiltration, and TBG. Multivariate analysis selected only TBG3 as a predictor of NLM (odds ratio, 9.55; 95% confidence interval [CI], 1.80-50.8; P = .008), and a prognostic factor for DSS (hazard ratio, 4.41; 95% CI, 1.34-14.5; P = .02). The sole predictor of NLM and the prognosis of early tongue SCC was TBG, indicating that it might help to select overwhelming risk patients.

The clinical study of prognostic factors in patients with early tongue squamous cell carcinoma in our department

The clinical study of prognostic factors in patients with early tongue squamous cell carcinoma in our department

Outcomes after up-front surgery and metronomic neoadjuvant chemotherapy with S-1 or UFT for early tongue squamous cell carcinoma.

Our aim was to investigate the disease-free survival in patients with tongue squamous cell carcinoma receiving metronomic neoadjuvant chemotherapy with 5-fluorouracil prodrugs (UFT or S-1) plus bleomycin compared with those who had up-front surgery retrospectively. In this retrospective study, 108 patients with stages I to II tongue squamous cell carcinoma who had undergone surgery were divided into the "surgery group" or "neoadjuvant chemotherapy group." A total of 41 patients received up-front surgery; 67 received metronomic neoadjuvant chemotherapy with UFT plus bleomycin (39) or S-1 plus bleomycin (28). The rate of disease-free survival was the primary outcome measure. Neoadjuvant 5-fluorouracil prodrugs did not correlate higher with improved disease-free survival than up-front surgery (72 and 54%, respectively; hazard ratio for recurrence or death, 0.54; 95% confidence interval [CI], 0.28 to 1.03; P = 0.06). Patients who received S-1 were more likely than those who received UFT to have pathological complete response (46% vs. 15%; P = 0.007). Neoadjuvant S-1 significantly improved disease-free survival as compared with up-front surgery (79% vs. 54%; hazard ratio, 0.41; 95% CI, 0.15 to 0.98; P = 0.04). However, neoadjuvant UFT did not improve disease-free survival as compared with up-front surgery (67% vs. 54%, respectively; hazard ratio, 0.66; 95% CI, 0.31 to 1.33; P = 0.24). Neoadjuvant S-1 chemotherapy, as compared with up-front surgery, significantly improved disease-free survival among patients with tongue squamous cell carcinoma. A choice of drugs before neoadjuvant metronomic chemotherapy is needed.

Setting of the surgical margin using optical instrument for treatment of early tongue squamous cell carcinoma

ObjectiveReveal the usefulness of loss of fluorescence visualization in the determination of surgical margin in early tongue oral squamous cell carcinoma (SCC). BackgroundSCC is often surrounded by oral epithelial dysplasia (OED), which can result in local recurrence. An optical instrument can be used to detect OED and SCC in oral mucosa, but whether it affects the prognosis after SCC surgery is unknown. Since 2010, we have performed visual examinations for fluorescence visualization loss at the Department of Oral and Maxillofacial Surgery, Tokyo Dental College in Chiba Hospital. The aim of this study was to clarify the usefulness of an optical instrument for treating early tongue SCC. Patients and methodsA total of 272 patients with primary T1-2N0 tongue SCC who underwent surgery between 1982 and 2016 at our hospital were selected. The surgical margin was at least 7 mm from the margin of fluorescence visualization loss. Outcomes were retrospectively investigated. ResultsAfter introduction of the optical instrument, 5-year overall survival and the local control rate were 93.9% and 97.1%, respectively (p = 0.440, p = 0.045). In all periods, the optical instrument group achieved a favorable prognosis. On intraoperative frozen section examination (including OED), the positive rate was 19.0% (p = 0.028). The positive rate of a pathological history in OED and SCC was 12.3% and 0% (p = 0.021, p < 0.001), respectively. ConclusionsThe optical instrument group achieved favorable results. This suggests that fluorescence visualization loss observed with an optical instrument is useful for deciding the surgical margin in early tongue SCC.

Neck lymphatic metastasis, surgical methods and prognosis in early tongue squamous cell carcinoma

Objective: To investigate the different pattern of neck lymph node metastasis, the choice of surgical methods and prognosis in early tongue squamous cell carcinoma. Methods: A total of 157 patients with early oral tongue squamous cell carcinoma were included in this study. Statistical analysis was performed to identify the pattern of lymph node metastasis, to determine the best surgical procedure and to analyze the prognosis. Results: The occurrence of cervical lymph node metastasis rate was 31%(48/157). Neck lymphatic metastasis was significantly related to tumor size (P=0.026) and histology differentiation type (P=0.022). The rate of metastasis was highest in level Ⅱ [33% (16/48)]. In level Ⅳ, the incidence of lymph node metastasis was 5%(7/157), and there was no skip metastases. The possibility of level Ⅳ metastasis was higher, when level Ⅱ (P=0.000) or Ⅲ (P=0.000) involved. The differentiation tumor recurrence, neck lymphatic metastasis and adjuvant radiotherapy were prognostic factors (P<0.05). Multivariate analyses revealed histology differentiation type, neck lymphatic metastases and adjuvant radiotherapy were the independent prognostic factors. Conclusions: Neck lymphatic metastasis rate is high in early tongue squamous cell carcinoma, simultaneous glossectomy and neck dissection should be performed. Level Ⅳ metastasis rate is extremely low, so supraomohyoid neck dissection is sufficient for most of the time. The histology differentiation type, neck lymphatic metastasis and adjuvant radiotherapy are independent prognostic factors.

Cytoplasmic neuropilin 2 is associated with metastasis and a poor prognosis in early tongue cancer patients

Neuropilin 2 (Nrp2) plays an important role in regulating lymphangiogenesis. Nrp2 expression in early tongue cancer was investigated to predict lymph node metastasis and the long-term prognosis. The relationships between clinicopathological variables of cT1–T2N0 tongue squamous cell carcinoma (SCC) and overexpression of Nrp2, vascular endothelial growth factor C (VEGFC), vascular endothelial growth factor receptor 3 (VEGFR3), and semaphorin 3F (Sema3F) were analyzed. Expression levels were compared using oral SCC cell lines. The Nrp2 gene was silenced to determine the impact of Nrp2. Cytoplasmic Nrp2 overexpression predicted regional metastasis with sensitivity and specificity of 90.3% and 42.1%, respectively. Cytoplasmic Nrp2 overexpression (P<0.001) and VEGFC overexpression (P=0.006) were significantly related to regional metastasis (Student t-test). However, only cytoplasmic Nrp2 overexpression was an independent prognostic factor for both disease-free survival (DFS; P=0.008) and overall survival (OS; P=0.016) (Cox regression); the risk of recurrence was 12-times higher (P=0.015) and risk of mortality was 8-times higher (P=0.016). Co-localization of Nrp2 and VEGFC was greater within the cytoplasm of aggressive cell lines (HN12 and RCa-T). Nrp2 plays a role in tumourigenesis; VEGFC supplementation cannot rescue the biological function of Nrp2 in Nrp2-depleted cell lines. Cytoplasmic Nrp2 overexpression is associated with decreased OS and DFS. Cytoplasmic Nrp2 overexpression may be a reliable diagnostic and prognostic marker for early tongue SCC.

Is prophylactic neck dissection for early tongue squamous cell carcinoma (cT1-2, cN0 neck) an evidence-based choice? A systematic review and meta-analysis

Is prophylactic neck dissection for early tongue squamous cell carcinoma (cT1-2, cN0 neck) an evidence-based choice? A systematic review and meta-analysis

Tumor Infiltration Depth as Predictor of Nodal Metastasis in Early Tongue Squamous Cell Carcinoma

A retrospective longitudinal study was conducted to identify the cutoff value of infiltration depth for predicting the risk of lymph node metastasis of the neck in a well-defined population of surgically treated patients affected by stage T1 to T2 oral squamous cell carcinoma of the tongue. Sixty-seven patients were enrolled in this study. Forty-four patients (65.5%) had pN0 status and 23 (34.5%) had pN(+) status. Thirty-five positive lymph nodes were analyzed. The median follow-up for these patients was 51.4 months. The mean infiltration depth of the N-negative group was 2.4 mm; this was substantially different from the mean value observed in the N-positive group at 5.5 mm. A meaningful cutoff was identified at an infiltration depth value of 4 mm. Infiltration depth was identified as an important predictor for neck nodal status. In this specific population, mortality was associated with increasing tumor infiltration depth.

Abstract 4811: Pro-oncogenic role of NOTCH1 in early tongue squamous cell carcinoma

Abstract Notch pathway play a context-dependent tumor-suppressive or pro-oncogenic role in solid tumors and hematological malignancies. In head and neck cancer, inactivating mutations in NOTCH1 are associated with poor prognosis. Here we perform meta-analysis of DNA copy number and gene expression profiling of NOTCH signaling pathway genes in 35 paired primary T1 and T2 stage tongue tumors, comprising of Notch ligands, receptors and target genes. We find 32% of primary tongue squamous cell carcinoma (TSCC) tumors amplify NOTCH signaling pathway components; and over express activated NOTCH1based on immuno-histochemical staining in an additional series of 50 surgically resected paired TSCC tumors. Interestingly, these alterations: amplification at Notch ligand DLL3 (χ2 = 7.575, P = 0.023); over expression of Notch pathway target gene HEY2 transcript (χ2 = 9.885, P = 0.007); and expression of activated NOTCH1 (χ2 = 7.575, P = 0.023) positively correlate with N+ve and non- smoking status of patients. In a parallel effort, we characterized four HNSCC cell lines– NT8E, OT9, AW13516, and AW8507– established from Indian patients using whole exome, whole transcriptome sequencing and SNP array assays. Significant amplification and over expression of NOTCH signaling pathway components were observed in AW13516 and NT8E cells. Inhibition of NOTCH activation by gamma secretase inhibitor or shRNA mediated knockdown of NOTCH1 could inhibit transformation, survival, migration and invasion of NT8E cells. Taken together, we present that activation of Notch signaling pathway in a subset of TSCC patients is associated with nodal positivity and non-smoking status among early tongue cancer patients. Citation Format: Pawan Upadhyay, Jyotirmoi Aich, Vidyalakshmi Sethunath, Prachi Dani, Sadhana Kannan, Pratik Chandrani, Kavitha Sonawane, Beamon Agarwal, Shubhada Kane, Sudhir Nair, Amit Dutt. Pro-oncogenic role of NOTCH1 in early tongue squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4811. doi:10.1158/1538-7445.AM2015-4811

Neurovascular Invasion and Histological Grade Serve as the Risk Factors of Cervical Lymph Node Metastases in Early Tongue Squamous Cell Carcinoma.

The objectives of this study were to analyze the regional characteristics of the cervical lymph node metastasis and to investigate the factors associated with the risk of lymph node involvement. One hundred seventy-one patients suffering from early primary squamous cell carcinoma (SCC) of the tongue (cT1-2N0) were enrolled. Gender, age, growth site, T stage, histological grade, and neurovascular invasion were statistically analyzed by K-M survival analysis and Cox multivariate analysis to evaluate the relationship between the factors and the neck lymph node metastasis. Of the 171 cases divided into the neck dissection group and observation group, 40 ended up with lymph node metastasis, of which 17 were metastasized to level I, 27 to level II, 10 to level III, 2 to level IV, and 1 to level V. Histological grade and neurovascular invasion were significantly associated with lymph node involvement in univariate and multivariate analyses. Age distribution was found to be significantly associated with the lymph node metastasis in multivariate analysis. The metastasis of early tongue SCC has a certain regularity at different sites. Age was not a critical risk factor for cervical lymph node metastasis after surgery. Tumor size was suspected to exert a negative effect on metastasis by influencing tumor invasion. Histological grade and neurovascular invasion were significantly associated with the risk of cervical lymph node metastasis of early tongue SCC.

A role for panendoscopy? Second primary tumour in early stage squamous cell carcinoma of the oral tongue.

Panendoscopy is routinely used for the identification of occult second primary tumours in head and neck squamous cell carcinoma. However, its role in low risk subgroups, particularly non-smoking, non-drinking patients and patients presenting with early stage oral cavity lesions, is debatable. The records of 112 patients with T₁ or T₂ oral tongue squamous cell carcinoma were retrospectively reviewed. Demographic, disease characteristics and survival data were collected. Average follow-up duration was 71.7 months (range, 3.6-238.3 months). Thirty-five patients died within this period. Thirteen second primary events were identified in 11 patients, with all but 2 tumours in the oral cavity or oropharynx. There was a single synchronous primary - a lung adenocarcinoma; all other events were metachronous. No non-smoking, non-drinking patients re-presented with a second primary tumour; tobacco and alcohol use are clearly risk factors for development of a second primary tumour. The role of panendoscopy for identifying synchronous primary tumours in patients with early stage oral tongue squamous cell carcinoma should be re-evaluated, particularly in non-smoking, non-drinking patients who are at low risk of second primary development. Close follow up with regular clinical examination including flexible fibre-optic endoscopy may be sufficient in this subgroup.

Does HMGB1 predict occult neck lymph node metastasis in early tongue carcinoma? A case-control study of 26 patients.

This study examined whether the occurrence of late neck metastasis in early tongue squamous cell carcinoma can be predicted by evaluating HMGB1 (high mobility group box 1) expression in the primary lesion. A case-control study was conducted. The cases comprised 10 patients with late neck metastasis. The controls consisted of 16 patients without recurrence. All were examined immunohistochemically for HMGB1 protein expression. The odds ratio for late neck metastasis in relation to HMGB1 was estimated. RESULTS for HMGB1 were dichotomised into positive staining scores (score, 5-7) and negative scores (0-4). Six cases (60 per cent) and four controls (25 per cent) were HMGB1-positive. Although no significant result was seen, compared with HMGB1-negative patients the odds ratio for late neck metastasis in HMGB1-positive patients was 3.8 (95 per cent confidence interval, 0.6-26.5) after adjusting for other factors. In the present study, immunohistochemical study of HMGB1 in early tongue squamous cell carcinoma did not appear to be very useful for predicting occult neck metastasis. Further study is necessary to clarify the relationship between HMGB1 expression and late neck metastasis in early tongue squamous cell carcinoma.