Dynamic alterations of circulating T lymphocytes and the clinical response in patients with head and neck squamous cell carcinoma treated with nivolumab.

Cancer immunotherapy using immune checkpoint inhibitors (ICIs) has been recognized as a novel therapeutic option for head and neck squamous cell carcinoma (HNSCC). However, only approximately 20-30% of patients with recurrent/metastatic (R/M) HNSCC benefit. Moreover, the mechanisms underlying the response to ICIs remain unclear. We investigated the proportion, activation status, and expression level of immune checkpoint molecules in circulating T cell subsets in R/M HNSCC patients treated with nivolumab using flow cytometry and mass cytometry, and then determined whether treatment response was associated with these values. We also assessed the changes in the frequency of tumor-associated antigens, MAGE-A4 and p53, -specific T cells prior to and after nivolumab treatment using the IFN-γ ELISPOT assay. The proportion of activated CD4+ and CD8+ TEMRA cells significantly increased in the disease-controlled patients but not in disease-progressed patients. As expected, the expression of PD-1 in T cells markedly decreased regardless of the therapeutic response. Meanwhile, T cell immunoglobulin mucin-3 expression on CD8+ T cells was significantly higher in patients with disease progression than in disease-controlled patients after treatment. The frequency of the tumor-associated antigens, MAGE-A4- and p53-specific T cells, was not correlated with clinical responses; however, in the disease-controlled patients, the frequency of MAGE-A4-specific T cells was significantly augmented. We concluded that in R/M HNSCC patients treated with nivolumab, circulating T cells show dynamic alterations depending on treatment efficacy. An analysis of the immunokinetics of circulating T cells could thus provide new insights into rational therapeutic strategies in cancer immunotherapy for HNSCC.

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.

[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.

[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.

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.

Subglottic Schwannoma: a report of a rare case that was treated with medial thyrotomy.

We present a rare case of primary subglottic schwannoma in a 51-year-old man. He presented with subacute dyspnea and progressively worsening stridor. Videoendoscopy revealed the presence of a submucosal mass in the subglottic area, which measured 2 cm in diameter and had occluded approximately 80% of the lumen. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a tumor arising from the left posterior wall of the subglottis and extending from the level of the cricoid cartilage to the first tracheal ring. After tracheostomy for airway management, subglottic schwannoma was diagnosed via fiberscopy-assisted punch biopsy. We removed the tumor via a medial thyrotomy (laryngofissure), and the post-excisional raw surface of the cricoid and tracheal cartilage was covered with a free buccal mucosal flap, which was attached using absorbable sutures and fibrin glue. No complications including recurrent nerve palsy developed after the procedure, and early postoperative ambulation was successfully performed. The patient is currently well, and the subglottic wound is clear. Although long-term follow-up is required, medial thyrotomy and coverage of the exposed cartilage with a free buccal mucosal flap is more effective for large subglottic schwannomas than laryngeal or tracheal resection with permanent tracheal tunnel formation from the viewpoint of phonation disability and the risk of complications.

Efficacy of immune checkpoint inhibitor treatment for head and neck mucosal melanoma recurrence in patients treated with carbon-ion radiotherapy.

BACKGROUND: Carbon-ion radiotherapy (C-ion RT) is effective for head and neck mucosal melanoma (HN-MM), including radioresistant mucosal melanoma. Melanoma also responds effectively to immune checkpoint inhibitors (ICIs). Data on the efficacy and safety of ICIs for HN-MM are insufficient. AIMS: To analyze the efficacy and safety of ICI salvage therapy in patients with HN-MM recurrence after C-ion RT. METHODS AND RESULTS: This retrospective study analyzed the medical records of 52 patients with HN-MM treated with C-ion RT between 2012 and 2020. A dose of 57.6 or 64.0 Gy (relative biological effectiveness) was provided in 16 fractions. The primary endpoint was 3-year overall survival (OS) rate. The median follow-up time was 26.8 months for all patients. A total of 29 patients had local recurrence or distant metastasis, and 16 patients who received ICI therapy. The 3-year OS rate in the ICI group (n = 16) and best supportive care group (n = 13) were 53.8% and 0.0%, respectively (p = 0.837); the difference was not statistically significant. There were no deaths after 1 year among patients who underwent ICI therapy. No adverse events associated with C-ion RT were related to or exacerbated by ICI. CONCLUSION: ICI salvage therapy is effective and safe for patients with HN-MM recurrence after C-ion RT.

The Efficacy of Radiotherapy without Surgery for External Auditory Canal Squamous Cell Carcinoma.

External auditory canal (EAC) cancer is a rare disease for which there are no adequate evidence-based treatment strategies. Radiotherapy is often used as the initial treatment to preserve the organ. This study aimed to elucidate the efficacy of radiotherapy for EAC squamous cell carcinoma (SCC). Patients with T1 disease were treated with radiotherapy alone. Patients with T2-4 disease were treated with chemoradiotherapy. The median follow-up period was 30.4 months. The 3-year local control (LC) rate for all patients was 51%, the disease-free survival (DFS) rate was 44%, and the overall survival (OS) rate was 73%. For T1-3 disease, the 3-year LC rate was 74%, DFS was 62%, and OS was 89%. However, for T4 disease, the 3-year LC rate was 17%, DFS was 17%, and OS was 50%. In a univariate analysis, only the T-category was a significant factor for LC and DFS (p = 0.006 and 0.02, respectively). All local recurrences were within the high-dose irradiated area. The results of this study suggest chemoradiotherapy can be an alternative to a combination of surgery and postoperative radiation for T1-3 SCC of the EAC. However, the efficacy of chemoradiotherapy in T4 cases was inadequate.

Carbon-ion Radiotherapy for Inoperable Head and Neck Bone and Soft-tissue Sarcoma: Prospective Observational Study.

BACKGROUND/AIM: Bone and soft-tissue sarcomas of the head and neck have very poor prognoses. This prospective study aimed to investigate the efficacy and safety of carbon-ion radiotherapy (C-ion RT) for bone and soft-tissue sarcoma of the head and neck. PATIENTS AND METHODS: The present study was a prospective clinical study that included 10 consecutive patients diagnosed with bone and soft-tissue sarcoma of the head and neck who were treated with C-ion RT between 2012 and 2018 at our institution. C-Ion RT consisted of 70.4 Gy (relative biological effectiveness) in 16 fractions. RESULTS: The 3-year local control, overall survival, and progression-free survival rates for patients overall were 72.9%, 77.8%, and 36%, respectively. CONCLUSION: The present study demonstrated the efficacy of C-ion RT for bone and soft-tissue sarcoma of the head and neck; adverse events were within the expected range.

Angiotensin II receptor blocker-induced angioedema in the oral floor and epiglottis.

We report the rare case of angioedema (also known as Quincke edema), which was induced by valsartan, an angiotensin II receptor blocker (ARB). ARBs are a new class of antihypertensive agent that is developed to exclude the adverse effects of angiotensin-converting enzyme inhibitors. In theory, ARBs do not contribute to the occurrence of angioedema because they do not increase the serum level of bradykinin, the responsible substance for angioedema. However, some reports of ARB-induced angioedema have recently been published. In this study, we present the forth case and the first Asian case of angioedema due to valsartan, which is one of the ARBs. Otolaryngologist should be wary of the prescribing ARB and discontinue ARBs treatment soon, if angioedema is recognized.

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.

Molecular profiling of circulating tumor cells predicts clinical outcome in head and neck squamous cell carcinoma.

OBJECTIVES: The relationship between the molecular profiling of circulating tumor cells (CTCs) and clinical factors is a challenge. In this study, we performed molecular detection and characterization of CTCs in patients with head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: CTCs captured by microfilter were analyzed for the expression of multiple epithelial markers (EPCAM, MET, KRT19, and EGFR) by RT-qPCR. The CTCs-positive samples were further analyzed for the expression of 10 genes (PIK3CA, CCND1, SNAI1, VIM, CD44, NANOG, ALDH1A1, CD47, CD274, and PDCD1LG2). Finally, we analyzed whether the molecular profiling of CTCs was associated with clinical factors. RESULTS: Twenty-eight (63.6%) of the 44 HNSCC patients were positive for at least one epithelial-related gene. CTC-positivity was significantly correlated with treatment resistance (p = 0.0363), locoregional recurrence (p = 0.0151), and a shorter progression-free survival (PFS) (p = 0.0107). Moreover, the expression of MET in CTCs was associated with a shorter PFS (p = 0.0426). Notably, patients with CD274-positive CTC showed prolonged PFS (p = 0.0346) and overall survival (p = 0.0378) compared to those with CD274-negative CTC. CONCLUSION: Our results suggest that molecular profiling characterized by the gene expression of CTCs influences clinical factors in patients with HNSCC.

Molecular phenotypes of circulating tumor cells and efficacy of nivolumab treatment in patients with head and neck squamous cell carcinoma.

The emergence of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Biomarkers of the therapeutic efficacy of ICIs have been extensively investigated. In this study, we aimed to analyze whether molecular phenotypes of circulating tumor cells (CTCs) are associated with treatment responses and clinical outcomes in patients with R/M HNSCC treated with nivolumab. Peripheral blood samples were collected before treatment initiation and after four infusions of nivolumab. CTCs isolated by depletion of CD45-positive cells were analyzed to determine the expression of EPCAM, MET, KRT19, and EGFR using real-time quantitative polymerase chain reaction. CTC-positive samples were analyzed to determine the expression of PIK3CA, CCND1, SNAI1, VIM, ZEB2, CD44, NANOG, ALDH1A1, CD47, CD274, and PDCD1LG2. Of 30 patients treated with nivolumab, 28 (93.3%) were positive for CTCs. In 20 CTC-positive patients, molecular alterations in CTCs before and after nivolumab treatment were investigated. Patients with MET-positive CTCs had significantly shorter overall survival than those with MET-negative CTCs (p = 0.027). The expression level of CCND1 in CTCs of disease-controlled patients was significantly higher than that of disease-progressed patients (p = 0.034). In disease-controlled patients, the expression level of CCND1 in CTCs significantly decreased after nivolumab treatment (p = 0.043). The NANOG expression in CTCs was significantly increased in disease-controlled patients after nivolumab treatment (p = 0.036). Our findings suggest that the molecular profiling of CTCs is a promising tool to predict the treatment efficacy of nivolumab.

Expression of immune-regulatory molecules in circulating tumor cells derived from patients with head and neck squamous cell carcinoma.

OBJECTIVES: Circulating tumor cells (CTCs) are cells that have shed from tumor tissue into the bloodstream, and the detection and characterization of CTCs in head and neck squamous cell carcinoma (HNSCC) still remain a challenge. MATERIALS AND METHODS: CTCs were isolated from 30 patients with HNSCC with recurrent and/or distant metastasis, via the depletion of CD45-positive cells with magnetic beads and the expression of multiple epithelial markers (CK19, EpCAM, EGFR, and c-Met) was analyzed by RT-qPCR with a low concentration of RNA from the CTC population. We next investigated the expression of the immune-regulatory molecules, PD-L1, PD-L2, and CD47, in CTC-positive patients and the PD-L1 expression in CTCs was compared with that in tumor tissues. RESULTS: Twenty-four (80.0%) of the 30 patients were positive for at least one epithelial-related gene. Among the 24 CTC-positive patients, 19 (79.2%), 20 (83.3%), and 17 (70.8%) patients were positive for CD47, PD-L1, and PD-L2, respectively. Interestingly, the expression of these three immune-regulatory molecules was positively correlated to each other. As expected, PD-L1 expression in the tumor tissue did not correspond completely with that in the CTCs. CONCLUSION: Although clinical application and/or characterization of CTCs are still developing, our findings suggest that the CTCs are rapidly becoming a powerful tool in cancer treatments that involve the use of immune checkpoint inhibitors.

Carbon-ion radiotherapy combined with chemotherapy for head and neck mucosal melanoma: Prospective observational study.

This study aimed to evaluate the efficacy of carbon-ion radiotherapy in combination with chemotherapy using dacarbazine, nimustine, and vincristine (DAV therapy) in mucosal melanoma. Twenty-one patients with clinically localized mucosal melanoma of the head and neck were enrolled. The primary endpoint was 3-year overall survival (OS). Secondary endpoints included local control, progression-free survival (PFS), and adverse event occurrence. Carbon-ion radiotherapy with a dose of 57.6-64.0 Gy (relative biological effectiveness) in 16 fractions was delivered concurrently with DAV therapy, and 2 cycles of adjuvant DAV therapy were administered every 6 weeks. The median follow-up periods were 15.5 months for all patients, and 31.2 months for 12 surviving patients. All patients had locally advanced T4a or T4b disease in the rhino-sinus area. In 16 patients (76.2%), 3 cycles of planned DAV therapy were completed. The 3-year OS and PFS rates were 49.2% and 37.0% respectively. The 3-year local control rate was 92.3%. Eleven patients (52%) developed distant metastasis, which was the most frequent pattern of the first failure. Commonly presenting acute grade 2-3 toxicities associated with radiotherapy and chemotherapy were mucositis (11 patients [53%]) and leukopenia (9 patients [43%]), which improved with conservative therapy. None of the patients developed grade 3 or greater late toxicities. Carbon-ion radiotherapy in combination with DAV therapy led to excellent local control for advanced mucosal melanoma within acceptable toxicities. The efficacy of additional DAV therapy in improving survival was weaker than expected as distant metastases still occurred frequently. Trial registration no. UMIN000007939.

Membrane properties of excitatory and inhibitory neurons in the rat prepositus hypoglossi nucleus.

The prepositus hypoglossi nucleus (PHN) is thought to be a neural structure involved in transforming eye or head velocity signals into eye position signals for horizontal eye movements. In this study, we investigated the relationship between electrophysiological membrane properties and expression patterns of cellular markers for excitatory and inhibitory neurons by whole-cell patch clamp recordings followed by reverse transcription polymerase chain reaction (RT-PCR) analysis in rat brainstem slices. Three types of voltage response properties, namely afterhyperpolarization (AHP), firing pattern, and response to hyperpolarizing current pulses, were characterized in each neuron. Following RT-PCR analysis, we identified PHN neurons as either glutamatergic (n = 22) or GABAergic (n = 43), although a small number of cholinergic (n = 2) and glycinergic neurons (n = 1) were also identified. Both glutamatergic and GABAergic neurons showed a wide variety of membrane properties; however, we found several characteristic relationships between neuronal type and membrane properties. Most neurons exhibiting (i) AHP without a slow component, (ii) a firing pattern with a delay in the generation of the first spike, (iii) a firing pattern with a transient burst and (iv) a firing pattern with a prolonged initial interspike interval were GABAergic. On the other hand, glutamatergic neurons were primarily characterized by a low firing rate. These results indicate that there is a close relationship between specific electrophysiological membrane properties and expression of chemical markers in some types of glutamatergic and GABAergic PHN neurons.

Expression of thymidylate synthase and dihydropyrimidine dehydrogenase in adenoid cystic carcinoma of the head and neck: correlation with clinical outcome.

The purpose of this study was to estimate the possibility of using thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and p53 as predictive values of clinical outcome in adenoid cystic carcinoma (ACC). The expressions of TS, DPD, and p53 were examined with immunohistochemistry in 27 ACC patients, and the association with clinicopathological factors was determined. Cases with high DPD expression had significantly higher distant metastasis rates compared to those with low DPD expression (p=0.001), whereas neither TS nor p53 expression showed any significant correlation to clinicopathological factors. Interestingly, six of 14 early-stage patients had distant metastases and all of their tumors showed high DPD expression. Kaplan-Meier analysis revealed that a solid histological pattern and distant metastasis correlated with a poor prognosis. In early-stage patients, whose tumor was completely resected, those with high TS or DPD expression had a worse prognosis compared to those with low expression, but the difference did not reach statistical significance (TS, p=0.178; DPD, p=0.251). Our results suggest that assessment of DPD expression in ACC may be a useful tool in determining the mode of treatment as well as evaluating clinical outcome.

Concurrent chemoradiotherapy with conventional fractionated radiotherapy and low-dose daily cisplatin plus weekly docetaxel for T2N0 glottic cancer.

BACKGROUND: To assess the efficacy of concurrent chemoradiotherapy (CCRT) with daily low-dose cisplatin (CDDP) plus weekly docetaxel (DTX) for patients with T2N0 glottic cancer. METHODS: Between January 2004 and December 2013, 62 treatment-naive patients with histologically proven T2N0 glottic cancer were treated with concurrent chemoradiotherapy. Radiation therapy (RT; 2 Gy daily fractions up to a total dose of 66 Gy) was administered in combination with daily low-dose CDDP (6 mg/m2, five times a week), plus weekly DTX (10 mg/m2) for up to 4 weeks from the commencement of RT. RESULTS: Median duration of follow-up was 70 months. The actuarial 3-year and 5-year overall survival rates were 95% and 93%. The 3-year and 5-year cause-specific survival rates were both 100%. The actuarial 3-year and 5-year local control rates were 94% and 94%, respectively. Hematologic toxicity (neutoropenia of severity ≥ Grade 3) was observed in 8% of the patients, and non-hematologic toxicity (radiation mucositis of severity ≥ Grade 3) developed in one patient (2%). Radiation dermatitis of severity ≥ Grade 3 and laryngeal necrosis developed in one patient. CONCLUSION: CCRT with weekly DTX and low-dose CDDP appears to be a practical and safe modality and is expected to improve local control. TRIAL REGISTRATION: UMIN000025046 . Registered 1 October 2015, retrospectively registered.

Impact of a Multidisciplinary Round Visit for the Management of Dysphagia Utilizing a Wi-Fi-Based Wireless Flexible Endoscopic Evaluation of Swallowing.

OBJECTIVES: The management of dysphagia requires a multidisciplinary approach, especially in large-scale hospitals. We introduce a novel protocol using a Wi-Fi-based flexible endoscopic evaluation of swallowing (FEES) system and aim to verify its effectiveness in evaluation and rehabilitation of inpatients with dysphagia. METHOD: We conducted novel Wi-Fi-based FEES at the bedside using 3 iPads as monitors and recorders. Functional outcomes of swallowing in 2 different hospitals for acute care with conventional wired or wireless FEES were compared retrospectively. RESULTS: Using the wireless system, we could visit more patients in a short period of time. Furthermore, a large multidisciplinary team was able to be present at the bedside, which made it easy to hold discussions and rapidly devise appropriate rehabilitation strategies. Aspiration pneumonia recurred in a few cases following our intervention with wireless FEES. Functional oral intake score was significantly increased following the intervention. Moreover, the number of deaths during hospitalization using wireless FEES evaluation was lower than those observed using the conventional system. CONCLUSION: Wi-Fi-based wireless FEES system, the first of its kind, allowed our multidisciplinary team to easily and effectively assess inpatients with dysphagia by facilitating simple examinations and intensive transprofessional discussions for patient rehabilitation.

Expression of thymidylate synthase and dihydropyrimidine dehydrogenase in oral squamous cell carcinoma: possible markers as predictors of clinical outcome.

CONCLUSIONS: Our results suggest that assessment of dihydropyrimidine dehydrogenase (DPD) in oral squamous cell carcinoma (OSCC) may be a useful tool in evaluating clinical outcomes. OBJECTIVE: The purpose of this study was to estimate the possibility of using thymidylate synthase (TS) and DPD as predictive values of clinical outcomes in OSCC. MATERIALS AND METHODS: The expression of TS and DPD was examined by immunohistochemistry (IHC) and the real-time reverse transcription-polymerase chain reaction method in 23 patients with OSCC, and the association with clinicopathological factors was determined. Immunohistochemical expression of p53 and P-glycoprotein (P-gp) was also examined. RESULTS: Neither TS protein nor TS mRNA expression showed any significant correlation to clinicopathological factors. In contrast, the patients with high DPD expression had significantly higher levels of recurrence compared with those with low DPD expression (p = 0.016). Similarly, six of seven patients with relapse had higher DPD mRNA expression values than the median value in the patients examined. On the other hand, no association was observed between TS or DPD and p53 or P-gp expressions.