Predictive factors for false negatives following sentinel lymph node biopsy in early oral cavity cancer.

Prophylactic elective neck dissection (ND) with navigation surgery using radioisotope-based sentinel lymph node biopsy (SLNB) is non-inferior to elective ND in terms of survival but has an advantage in postoperative functional disability. We conducted a subgroup analysis to identify predictive factors for false-negative (FN)-SLNB in patients with early oral cavity cancer. This study is a supplementary analysis using the dataset of a previously reported randomized clinical trial on SLN navigation surgery for oral cancers. This study investigated the association of clinical and SLN-related factors with false-negative cases in the SLNB group. From 2011 to 2016, 275 patients were enrolled and randomly assigned to the ND and SLNB study groups, with 134 patients assigned to the SLNB group. In the SLNB group, seven cases with negative SLNs and neck recurrences were judged as FN-SLNBs according to the general definition. The number of detected SLNs with and without adjusting for the propensity score was significantly associated with FNs in the logistic analysis. FN-SLNB was associated with the number of identified SLNs, suggesting the need for careful postoperative monitoring for neck recurrence in patients with one or two identified SLNs after acquiring sufficient experience in the identification technique.

Two Different Tracts and Origin of Pyriform Sinus Fistula.

OBJECTIVE: Suppurative acute thyroiditis is caused by pyriform sinus fistula (PSF), and PSF frequently elicits deep neck abscess. However, complete fistulectomy is the ideal management of PSF, and studies on surgical findings of PSF are exceedingly rare. This study aimed to reveal the origins of PSF, each route, and clinical presentation. METHODS: This is a multicenter study. We have conducted 19 complete fistulectomies of PSF in Japan, analyzed routes of the fistulas, estimated the origins, and investigated their histological and clinical findings. RESULTS: No recurrence was observed in all cases. Five of 12 cases showed thymic and/or parathyroid tissues around the fistulas, passing inside the inferior horn of thyroid cartilage, were regarded as having 3rd pouch origin, and tended to have low frequency of severe deep neck abscess. The remaining 7 cases originated from the 4th pouch running outside of the horn and showed frequent severe infection. CONCLUSION: PSF have 2 different routes depending on their generation and may present different clinical manifestations.

Influence of ultraviolet irradiation treatment on porcelain bond strength of titanium surfaces.

To determine the effect of titanium (Ti) surface modification by ultraviolet irradiation (UVI) on the bond strength between Ti and porcelain. Grade 2 Ti plates were allotted to five groups: sandblasted (SA), 15 min UVI (UV), SA+5 min UVI (SA+UV5), SA+10 min UVI (SA+UV10), and SA+15 min UVI (SA+UV15). After surface treatment, porcelain was added. A precious metal (MC) was used for comparison with Ti. The effects of 24-h storage at room temperature versus thermal cycling only at 5 and 55°C in water were evaluated. Subsequently, the tensile strength of each sample was tested. Data were analyzed using one-way analysis of variance and the Tukey test. In both the room temperature and thermal cycling groups, the MC and SA+15 min UVI samples showed significantly greater bond strengths than the other samples (p<0.05). UVI processing efficiently increases the bond strength between porcelain and the Ti surface.

Circulating tumor cells in patients with head and neck squamous cell carcinoma: Feasibility of detection and quantitation.

BACKGROUND: The purpose of this study was to present our findings that because circulating tumor cells (CTCs) exist in extremely low numbers, their detection and quantification are challenging. METHODS: Peripheral blood samples were collected from 32 patients with head and neck squamous cell carcinoma (HNSCC), and were subjected to the CellSieve Microfiltration Assay using a low-pressure filtration system. The CTCs captured by the filter were stained with an antibody cocktail (anti-cytokeratin (CK) 8, 18, and 19, anti-epithelial cell adhesion molecule (EpCAM), and anti-CD45 antibodies). RESULTS: The CTCs were detected in 29 of 32 patients (90.6%). Although patients with advanced disease had a significantly higher number of CTCs, the clinical N classification was not associated with the CTC count. After treatment, the CTC count showed a significant decrease. CONCLUSION: The CTCs were successfully detected and quantified in patients with HNSCC by using a low-pressure filtration system equipped with precision microfilters. Further studies using a larger number of patient samples and/or molecular analysis of CTCs are warranted.

Prospective observational study of carbon-ion radiotherapy for non-squamous cell carcinoma of the head and neck.

To evaluate the efficacy and safety of carbon-ion radiotherapy for non-squamous cell carcinoma of the head and neck, 35 patients were enrolled in this prospective study. The primary end-point was the 3-year local control rate, and the secondary end-points included the 3-year overall survival rate and adverse events. Acute and late adverse events were evaluated according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up time for all patients was 39 months. Thirty-two and three patients received 64.0 Gy (relative biological effectiveness) and 57.6 Gy (relative biological effectiveness) in 16 fractions, respectively. Adenoid cystic carcinoma was dominant (60%). Four patients had local recurrence and five patients died. The 3-year local control and overall survival rates were 93% and 88%, respectively. Acute grade 2-3 radiation mucositis (65%) and dermatitis (31%) was common, which improved immediately with conservative therapy. Late mucositis of grade 2, grade 3, and grade 4 were observed in 11, one, and no patients, respectively. There were no adverse events of grade 5. Carbon-ion radiotherapy achieved excellent local control and overall survival rates for non-squamous cell carcinoma. However, the late mucosal adverse events were not rare, and meticulous treatment planning is required. Trial registration no. UMIN000007886.

Cancer-associated fibroblasts promote an immunosuppressive microenvironment through the induction and accumulation of protumoral macrophages.

Stromal cells in the tumor microenvironment (TME) closely interact with tumor cells and affect tumor cell behavior in diverse manners. We herein investigated the mechanisms by which cancer-associated fibroblasts (CAFs) affect the functional polarization of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC) in vitro and in human cancer samples. The expression of CD68, CD14, CD163, CD200R, CD206, HLA-G, CD80, and CD86 was higher in CD14-positive cells co-cultured with the culture supernatants of CAFs established from OSCC specimens (CAF-educated cells) than in control cells. The gene expression level of ARG1, IL10, and TGFB1 was increased in CAF-educated cells. CAF-educated cells suppressed T cell proliferation more strongly than control cells, and the neutralization of TGF-ß IL-10, or arginase I significantly restored T cell proliferation. We then investigated the relationship between the infiltration of CAFs and TAMs using tissue samples obtained from patients with OSCC. The infiltration of CAFs was associated with the numbers of CD68-positive and CD163-positive macrophages. It also correlated with lymphatic invasion, vascular invasion, lymph node involvement, and the TNM stage. The infiltration of CAFs was identified as an independent prognostic factor in OSCC. Our results indicate that CAFs play important roles in shaping the tumor immunosuppressive microenvironment in OSCC by inducing the protumoral phenotype of TAMs. Therapeutic strategies to reverse CAF-mediated immunosuppression need to be considered.

Clinical Outcomes of Definitive and Postoperative Radiotherapy for Stage I-IVB Hypopharyngeal Cancer.

BACKGROUND: Hypopharyngeal cancer is relatively rare disease and continues to have a poor prognosis. This study analyzed the efficacy and safety of radiotherapy for stage I-IVB hypopharyngeal cancer. PATIENTS AND METHODS: Between 2000 and 2015, 72 patients were treated with definitive radiotherapy and 29 patients with stage IVA were treated with postoperative radiotherapy. RESULTS: With definitive radiotherapy, the 3-year locoregional control rates for stage I-II, III, IVA, and IVB disease were 89%, 74%, 51% and 0%, respectively. The 3-year overall survival rates for patients with stage I-II, III, IVA and IVB disease were 84%, 89%, 55% and 15%, respectively. In patients with stage IVA disease treated with postoperative radiotherapy, 3-year locoregional control and overall survival rates were 83% and 75%, respectively, which were significantly better than those treated with definitive radiotherapy. CONCLUSION: Definitive radiotherapy was effective for stage I-III disease. Surgery and postoperative radiotherapy improved the survival rate of patients with stage IVA hypopharyngeal cancer.

[Sequential Chemoradiotherapy for Advanced Head and Neck Cancer: A Clinical Study with 33 Cases].

A total of 33 patients with advanced head and neck cancer (AHNC) treated with sequential chemoradiotherapy (SCRT) were retrospectively evaluated at Gunma University Hospital between 2009 and 2011. The regimen of SCRT was docetaxel, cisplatin, and fluorouracil (TPF)-based induction chemotherapy (ICT), accompanied by docetaxel and cisplatin-based concurrent chemoradiotherapy (CCRT), and oral administration of TS-1 after that. The response rate was 61%, the 3-year overall survival rate was 42%, the non-tumor-bearing survival rate was 27%, and the tumor-bearing survival rate was 15%. Fourteen of 33 patients were tumor-free, and their 3-year overall survival rate was surprisingly 86%. On the other hand, 3-year overall survival rate in the remaining 19 patients was significantly low. To select good response cases for ICT was important. In such cases, TPF should be applied repeatedly, which achieved a 61% response rate even in AHNC. A long-term TS-1 oral medication suppressed cancer regrowth and contributed to long-term survival.

Nivolumab-induced hypophysitis in a patient with advanced malignant melanoma.

The anti-programmed cell death-1 monoclonal antibody (mab), nivolumab has recently been approved for the treatment of unresectable or metastatic malignant melanoma and non-small-cell lung cancers in Japan. Ipilimumab, an anti-cytotoxic T lymphocyte antigen-4 mab for malignant melanoma that was approved earlier than nivolumab in Western countries, is known to frequently cause endocrine immune-related adverse events such as hypophysitis and thyroid dysfunction. We herein report a patient with advanced melanoma who appeared to develop hypophysitis as a consequence of the inhibition of PD-1 by nivolumab. One week after the 6th administration of nivolumab, the patient developed progressive fatigue and appetite loss. Laboratory data on admission for the 7th administration of nivolumab showed eosinophilia and hyponatremia. Since ACTH and cortisol levels were low, nivolumab was discontinued and a large dose of hydrocortisone (100 mg/d) was promptly administered intravenously. A magnetic resonance imaging scan revealed the mild enlargement of the anterior pituitary gland and thickening of the stalk with homogenous contrast. A detailed assessment of anterior pituitary functions with hypothalamic hormone challenges showed that hormonal secretions other than ACTH and TSH were normal. With a replacement dose of hydrocortisone (20 mg/d), the 7th administration of nivolumab was completed without exacerbating the patient's general condition. The present report provides the first detailed endocrinological presentation of nivolumab-induced hypophysitis showing the enlargement of the pituitary gland and stalk in a malignant melanoma patient in Japan. Oncologists and endocrinologists need to be familiar with potentially life-threatening hypophysitis induced by immune-checkpoint inhibitors.

Relationship between tumor-associated macrophage subsets and CD47 expression in squamous cell carcinoma of the head and neck in the tumor microenvironment.

Tumor-associated macrophages (TAM) have been classified into an immunostimulatory M1 subset against microbes and malignancies, and an immunoregulatory M2 subset that secretes immunosuppressive cytokines in order to repair tissues damaged by malignancies. The infiltration of M2 in the tumor microenvironment is known to facilitate immunosuppression and tumor-promoting properties. In the present study, we investigated the phagocytic potential of these macrophage subsets in oral squamous cell carcinoma (OSCC) in relation to the expression of CD47, the 'don't eat me' signal against macrophages. The macrophage subsets M1 (induced by GM-CSF and IFN-γ) and M2 (induced by M-CSF and IL-10) were derived from the CD14(+) cells of healthy donors. Phagocytosis of the CFSE-labeled CD47(+) cell line HSC-3 by M1/M2 was assessed using flow cytometry and suppressed by an anti-CD47 neutralizing antibody or CD47 siRNA. Furthermore, CD68(+) and CD163(+) macrophage subset counts infiltrating tumor tissue and the expression of CD47 on cancer cells were examined immunohistochemically in 74 cases of OSCC, and their relationships with clinicopathological parameters or prognoses were determined. The phagocytic potential of M1 was similar to that of M2 in vitro. Phagocytosis by M1 increased in a CD47-dependent manner by the neutralizing antibody and siRNA, but did not in M2. An immunohistochemical (IHC) analysis revealed that the expression of CD47 did not correlate with macrophage subsets in peritumoral tissue or with any clinicopathological parameters; however, the stronger expression of CD47 by cancer cells and larger number of total macrophages/M2 were independently related to shorter survivals. Our results suggest that the expression of CD47 by cancer cells is related to evasion from phagocytosis, particularly that by M1 in vitro. IHC results indicate that various mechanisms are involved in the engulfing potential of TAM subsets in vivo.

Decreasing expression of glucose-regulated protein GRP78/BiP as a significant prognostic predictor in patients with advanced laryngeal squamous cell carcinoma.

BACKGROUND: The immunoglobulin heavy chain binding protein (BiP)/glucose-regulated protein 78 (GRP78) is important in the endoplasmic reticulum stress, and is highly expressed in various human cancers. The clinical and pathological features of GRP78/BiP are unclear in patients with advanced laryngeal squamous cell carcinoma (SCC). The purpose of this study was to investigate the clinicopathological significance of GRP78/BiP as a prognostic marker for laryngeal SCC. METHODS: A total of 59 patients with advanced laryngeal SCC (stage III/IV) were analyzed, and tumor specimens were stained by immunohistochemistry for GRP78/BiP and Ki-67. Microvessel density was determined by immunohistochemical staining for CD34 and p53. RESULTS: Expression of GRP78/BiP was confirmed in 87% of cases. Decreased expression of GRP78/BiP was highly associated with positive expression of p53. Decreased GRP78/BiP expression was identified on multivariate analysis as an independent factor of decreased progression-free survival (PFS). CONCLUSION: GRP78/BiP was found to be commonly expressed in laryngeal SCC, whereas its downregulation was found to serve a significant prognostic role for predicting poor survival in patients with laryngeal SCC with advanced disease. GRP78/BiP may be a potentially attractive target for the treatment of various human neoplasms. © 2016 Wiley Periodicals, Inc. Head Neck 38: First-1544, 2016.

Expression of ER stress markers (GRP78/BiP and PERK) in adenoid cystic carcinoma.

CONCLUSION: A high GRP78/BiP expression was proved to be a significant marker for predicting poor outcome after surgery. GRP78/BiP may be a promising molecular target for treatment of ACC. BACKGROUND: The glucose-regulated protein GRP78/BiP plays a crucial role in the endoplasmic reticulum (ER) stress. The level of GRP78 is highly elevated in various human cancers, but the clinicopathological significance of GRP78/BiP remains controversial in patients with adenoid cystic carcinoma (ACC). METHODS: A total of 26 ACC patients were analyzed, and tumor specimens were stained by immunohistochemistry for GRP78/BiP, PERK, Ki-67, and microvessel density (MVD) determined by CD34. RESULTS: GRP78/BiP and PERK were highly expressed in 58% (15/26) and 35% (9/26), respectively. The high expression of GRP78/BiP was significantly associated with PERK, cell proliferation and angiogenesis.

[Prediction of Post-operative Lymph Node Metastasis with a Molecular Biological Test in Head and Neck Cancer].

We assessed herein the post-operative lymph node metastasis in head and neck cancer, using the One-step nucleotide amplification (OSNA) method targeting matrix metalloproteinase 7 (MMP-7). Compared with the pathological test, the molecular biological test revealed more lymph node metastasis, resulting in poor prognosis. Six cases, of which the number of lymph node metastasis was the same between pathological and molecular biological test, survived. On the other hand, three of four cases, in which number of lymph node metastasis in the molecular biological test were larger than the pathological test, died from metastasis. We concluded that the pathological test underestimated metastasis, and OSNA with MMP-7 was useful for the prediction of post-operative lymph node metastasis.

Immunosuppressive activity of cancer-associated fibroblasts in head and neck squamous cell carcinoma.

Cancer-associated fibroblasts (CAFs) have been shown to play an important role in angiogenesis, invasion, and metastasis. In the present study, we determined whether CAFs within the tumor microenvironment (TME) in head and neck squamous cell carcinoma (HNSCC) contributed to promoting immunosuppression and evasion from immune surveillance. Six pairs of CAFs and normal fibroblasts (NFs) were established from the resected tumor tissues of patients with HNSCC. The effects of CAFs and NFs on the functions of T cells were comparatively analyzed. CAFs expressed the co-regulatory molecules, B7H1 and B7DC, whereas NFs did not. The expression levels of cytokine genes, including those for IL6, CXCL8, TNF, TGFB1, and VEGFA, were higher in CAFs. T cell proliferation was suppressed more by CAFs or their supernatants than by NFs. Moreover, PBMCs co-cultured with the supernatants of CAFs preferentially induced T cell apoptosis and regulatory T cells over those co-cultured with the supernatants of NFs. A microarray analysis revealed that the level of genes related to the leukocyte extravasation and paxillin signaling pathways was higher in CAFs than in NFs. These results demonstrated that CAFs collaborated with tumor cells in the TME to establish an immunosuppressive network that facilitated tumor evasion from immunological destruction.

Expression of Amino Acid Transporters (LAT1 and ASCT2) in Patients with Stage III/IV Laryngeal Squamous Cell Carcinoma.

The aim of this study is to evaluate the clinicopathological significance of L-type amino acid transporter 1 (LAT1) expression in patients with advanced laryngeal squamous cell carcinoma (LSCC). A total of 73 patients with advanced LSCC were retrospectively reviewed. Tumor sections were stained by immunohistochemistry for LAT1, 4F2hc, system ASC amino acid transporter-2 (ASCT2), cell proliferation by Ki-67, microvessel density (MVD) determined by CD34 and p53. A positive LAT1, 4F2hc and ASCT2 expression (staining more than a quarter) in the primary sites were recognized in 85, 80 and 45 %, respectively, and a high LAT1, 4F2hc and ASCT2 expression (staining more than a half) yielded 48, 31 and 18 %, respectively. High expression of LAT1 was significantly associated with lymph node metastasis, 4F2hc, ASCT2, Ki-67 and p53. The expression of LAT1 was significantly correlated with ASCT2, 4F2hc, cell proliferation, and MVD. By univariate analysis, there was no statistically significant relationship between LAT1 expression and prognosis in advanced LSCC. LAT1, 4F2hc and ASCT2 were highly expressed in patients with advanced laryngeal cancer. Our study suggests that the expression of LAT1 plays a crucial role in the metastasis and tumor progression in advanced LSCC.

(18)F-FDG uptake on PET correlates with biological potential in early oral squamous cell carcinoma.

CONCLUSION: The maximum standardized uptake value (SUVmax) of early oral squamous cell carcinoma (OSCC) may have a role as an imaging biomarker for assessment of malignant potential, including cell metabolism and angiogenesis. OBJECTIVE: The usefulness of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) has been proven in various cancers, including OSCC. Moreover, in several carcinomas, the SUVmax of the tumor has been shown to correlate with the histological type, tumor stage, differentiation, and prognosis. Here, we investigated whether the SUVmax of early OSCC was associated with the biological features. METHODS: Twenty-seven patients with newly diagnosed early OSCC who underwent preoperative FDG-PET and curative surgical resection were included in this study. Tumor sections were stained by immunohistochemistry for glucose transporter 1 (GLUT1), L-type amino acid transporter 1 (LAT1), CD98, microvessels (CD34), cell proliferation marker (Ki-67), and cell cycle regulator (p53). The correlation between SUVmax and clinicopathological findings or the expression level of these molecules was analyzed. RESULTS: SUVmax of primary OSCC was significantly higher in patients with T2 stage. Moreover, patients whose tumors showed vascular invasion had a tendency to show higher SUVmax. A significant correlation was observed between SUVmax and the expression of LAT1 or microvessel density.

Immunological significance of the accumulation of autophagy components in oral squamous cell carcinoma.

The immunological significance of autophagy in the tumor microenvironment remains unclear. To explore the relationship between autophagy and anti-tumor immune responses, we investigated the expression of autophagy-related proteins and infiltration of immune cells using immunohistochemistry (IHC). The expression of three representative autophagy components, LC3, Beclin-1 and p62/SQSTM1, as well as the number of dendritic cells (DC), T cells and NK cells were examined by IHC in 74 patients with oral squamous cell carcinoma (OSCC). The relationship between the expression of autophagy-associated molecules and various clinicopathological parameters was also evaluated. The expression of both LC3 and p62/SQSTM1 in the peripheral site significantly correlated with an increase in the infiltration of T cells. Furthermore, the expression of p62/SQSTM1 and Beclin-1 correlated with that of HLA class I and class II in tumor cells, respectively. In addition, several unfavorable clinicopathological parameters correlated with an increase in the expression of LC3 in the peripheral site. The correlation observed between LC3 or p62/SQSTM1 and the infiltration of T cells suggests that autophagy may actively mobilize immune cells toward the cancer bed. Meanwhile, the three autophagy-associated proteins examined were linked to malignant potential and an unfavorable prognosis.

Successful management of hypoparathyroidism following total thyroidectomy with vitamin D(3) alone.

OBJECTIVE: To assess the efficacy and safety of a single administration of vitamin D3 for postoperative hypoparathyroidism. PATIENTS AND METHODS: Twelve patients with postoperative hypoparathyroidism were enrolled for this study. They had taken calcium and vitamin D3 orally after the surgery and had shown no symptoms of hypoparathyroidism. Then, all patients had changed their regimen to a single administration of vitamin D3 (1α(OH)D3) with monitoring of serum calcium, urine calcium (u-Ca) and creatinine (u-Cre). The dose of vitamin D3 was started at 2.0µg/day and appropriately adjusted to maintain the ratio of u-Ca and u-Cre (u-Ca/u-Cre) at less than 0.3. The physical findings were carefully checked and the serum intact-parathyroid was also estimated. Those data and physical findings were monitored for at least two years. RESULT: The maintenance dose of vitamin D3 varied from 0.5 to 3.5µg/day, and the mean dose was 2.04µg/day. All patients tolerated changes of regimen without any symptoms of hyper-/hypocalcemia. CONCLUSION: A single administration of vitamin D3 is not only safe but also an easy and cost-effective regimen. This also makes drug control easy and worthwhile both for patients and clinicians. LEVEL OF EVIDENCE: 2c.

Alteration of cancer stem cell-like phenotype by histone deacetylase inhibitors in squamous cell carcinoma of the head and neck.

Recent progression in the understanding of stem cell biology has greatly facilitated the identification and characterization of cancer stem cells (CSCs). Moreover, evidence has accumulated indicating that conventional cancer treatments are potentially ineffective against CSCs. Histone deacetylase inhibitors (HDACi) have multiple biologic effects consequent to alterations in the patterns of acetylation of histones and are a promising new group of anticancer agents. In this study, we investigated the effects of two HDACi, suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA), on two CD44+ cancer stem-like cell lines from squamous cell carcinoma of the head and neck (SCCHN) cultured in serum-free medium containing epidermal growth factor and basic fibroblast growth factor. Histone deacetylase inhibitors inhibited the growth of SCCHN cell lines in a dose-dependent manner as measured by MTS assays. Moreover, HDACi induced cell cycle arrest and apoptosis in these SCCHN cell lines. Interestingly, the expression of cancer stem cell markers, CD44 and ABCG2, on SCCHN cell lines was decreased by HDACi treatment. In addition, HDACi decreased mRNA expression levels of stemness-related genes and suppressed the epithelial-mesencymal transition phenotype of CSCs. As expected, the combination of HDACi and chemotherapeutic agents, including cisplatin and docetaxel, had a synergistic effect on SCCHN cell lines. Taken together, our data indicate that HDACi not only inhibit the growth of SCCHN cell lines by inducing apoptosis and cell cycle arrest, but also alter the cancer stem cell phenotype in SCCHN, raising the possibility that HDACi may have therapeutic potential for cancer stem cells of SCCHN.

Clinicopathological significance of L-type amino acid transporter 1 (LAT1) expression in patients with adenoid cystic carcinoma.

The expression of L-type amino acid transporter 1 (LAT1) is correlated with tumor cell growth and survival. However, the clinicopathological significance of LAT1 expression in adenoid cystic carcinoma (ACC) remains to be elucidated. The aim of this study is to investigate the clinicopathological significance of LAT1 expression in ACC. A total of 30 patients with ACC were retrospectively reviewed. Tumor sections were stained by immunohistochemistry for LAT1, p53, and CD98, and cell proliferation and microvessel density (MVD) were determined by Ki-67 and CD34, respectively. High LAT1 and CD98 expression were observed in 27 % (8/30) and 23 % (7/30) of samples, respectively (p > 0.999). The high expression of LAT1 was significantly correlated with cell proliferation (Ki-67) and the cell cycle regulator p53. By univariate analysis, solid histological pattern, maxillary tumor site, LAT1, CD98, Ki-67 and p53 were significantly associated with poor prognosis. Multivariate analysis demonstrated that the high expression of LAT1 was an independent prognostic factor for predicting poor prognosis after surgical resection. LAT1 is a promising clinical marker to predict the outcome after surgery in patients with ACC.