scholarly journals Monocarboxylate transporter-1 (MCT1) protein expression in head and neck cancer affects clinical outcome

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Martin Leu ◽  
J. Kitz ◽  
Y. Pilavakis ◽  
S. Hakroush ◽  
H. A. Wolff ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Protein Expression ◽  
Head And Neck ◽  
Cox Regression ◽  
Locally Advanced ◽  
Monocarboxylate Transporter ◽  
Positive Staining ◽  
Monocarboxylate Transporter 1 ◽  
Prognostic Features ◽  
Hpv Status

AbstractTreatment of locally advanced, unresectable head and neck squamous cell carcinoma (HNSCC) often yields only modest results with radiochemotherapy (RCT) as standard of care. Prognostic features related to outcome upon RCT might be highly valuable to improve treatment. Monocarboxylate transporters-1 and -4 (MCT1/MCT4) were evaluated as potential biomarkers. A cohort of HNSCC patients without signs for distant metastases was assessed eliciting 82 individuals eligible whereof 90% were diagnosed with locally advanced stage IV. Tumor specimens were stained for MCT1 and MCT4 in the cell membrane by immunohistochemistry. Obtained data were evaluated with respect to overall (OS) and progression-free survival (PFS). Protein expression of MCT1 and MCT4 in cell membrane was detected in 16% and 85% of the tumors, respectively. Expression of both transporters was not statistically different according to the human papilloma virus (HPV) status. Positive staining for MCT1 (n = 13, negative in n = 69) strongly worsened PFS with a hazard ratio (HR) of 3.1 (95%-confidence interval 1.6–5.7, p < 0.001). OS was likewise affected with a HR of 3.8 (2.0–7.3, p < 0.001). Multivariable Cox regression confirmed these findings. We propose MCT1 as a promising biomarker in HNSCC treated by primary RCT.

scholarly journals Special Issue about Head and Neck Cancers: HPV Positive Cancers

2020 ◽  
Vol 21 (9) ◽  
pp. 3388 ◽  
Author(s):  
Panagiota Economopoulou ◽  
Ioannis Kotsantis ◽  
Amanda Psyrri
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Economic Status ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Papilloma Virus ◽  
High Risk Sexual Behavior ◽  
Hpv Status ◽  
Delays In Diagnosis

The oropharynx has become the leading primary site for Human Papilloma Virus (HPV)-associated head and neck cancer. HPV positive oropharyngeal squamous cell carcinoma (HPV+ OSCC) has emerged as an epidemic not easily recognized by many physicians, resulting in delays in diagnosis and management. HPV+ OSCC traditionally refers to younger, healthier patients with high economic status and high-risk sexual behavior and is related to improved prognosis. De-intensification strategies are being evaluated in ongoing clinical trials and if validated, might help spare severe morbidity associated with current cisplatin-based chemoradiotherapy, which is the standard of care for all patients with locally advanced head and neck cancer. On the other hand, whether HPV status represents an important prognostic factor for non-oropharyngeal sites remains to be elucidated.

CDKN2A copy number loss in HPV- and HPV+ head and neck cancer to indicate poor prognosis: An integrated genomic and clinical TCGA analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 6060-6060 ◽  
Author(s):  
William S. Chen ◽  
Ranjit Bindra ◽  
Allen Mo ◽  
Thomas Hayman ◽  
Zain Husain ◽  
...  
Keyword(s):  
Overall Survival ◽  
Head And Neck Cancer ◽  
Protein Expression ◽  
Head And Neck ◽  
Copy Number ◽  
Poor Prognosis ◽  
Copy Number Loss ◽  
P16 Protein ◽  
Hpv Status ◽  
Disease Free

6060 Background: HPV infection is associated with high p16 expression and relatively good prognosis in head and neck cancers. Analysis of CDKN2A, the gene that encodes the p16 tumor suppressor protein, may further elucidate the association between HPV status and prognosis in head and neck squamous cell carcinomas (HNSCCs). We aimed to identify whether CDKN2A copy number loss was associated with poor survival in HNSCCs stratified by HPV status. Methods: We analyzed The Cancer Genome Atlas (TCGA) head and neck cancer data, integrating genomic measurements with clinical metadata. Patients 85 years old or younger with a primary tumor in the oral cavity, oropharynx, hypopharynx, or larynx were included. Defining CDKN2A copy number loss as a relative log2 copy number ratio < −0.6, CDKN2A mRNA and p16 protein expression levels were compared to confirm significant differences in gene transcription and translation between the copy number loss and non-copy number loss patient groups. Overall survival (OS) and disease-free survival (DFS) were evaluated to characterize prognostic differences between genomic groups. Results: 397 patients negative for HPV (HPV−) and 91 patients positive for HPV (HPV+) HNSCC were identified. 139 HPV− patients and 9 HPV+ patients demonstrated CDKN2A copy number loss. The CDKN2A copy number loss group expressed significantly lower levels of CDKN2A mRNA and p16 protein than did the non-copy number loss group in both HPV+ and HPV− disease. Median OS for HPV− patients with and without CDKN2A copy number loss was 21.8 months and 46.0 months (P = 0.02). Median DFS was 12.0 and 19.4 months respectively (P < 0.05). Median OS for HPV+ patients with and without CDKN2A copy number loss was 12.7 months and 57.4 months (P = 0.004) and median DFS was 7.0 and 36.6 months respectively (P = 0.02). Conclusions: CDKN2A copy number loss was associated with low CDKN2A mRNA and p16 protein expression, with poor prognosis in terms of disease-free and overall survival.

scholarly journals Expression of Monocarboxylate Transporter 1 in Oral and Ocular Canine Melanocytic Tumors

2007 ◽  
Vol 44 (4) ◽  
pp. 449-457 ◽  
Author(s):  
Y. Shimoyama ◽  
Y. Akihara ◽  
D. Kirat ◽  
H. Iwano ◽  
K. Hirayama ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Mammalian Cells ◽  
Monocarboxylate Transporter ◽  
Intracellular Acidosis ◽  
Western Blots ◽  
Monocarboxylate Transporter 1 ◽  
Melanocytic Tumors ◽  
Oral Melanoma ◽  
Cell Membrane Protein ◽  
Histologic Subtypes

Solid tumors are composed of a heterogeneous population of cells surviving in various concentrations of oxygen. In a hypoxic environment, tumor cells generally up-regulate glycolysis and, therefore, generate more lactate that must be expelled from the cell through proton transporters to prevent intracellular acidosis. Monocarboxylate transporter 1 (MCT1) is a major proton transporter in mammalian cells that transports monocarboxylates, such as lactate and pyruvate, together with a proton across the plasma membrane. Melanocytic neoplasia occurs frequently in dogs, but the prognosis is highly site-dependent. In this study, 50 oral canine melanomas, which were subdivided into 3 histologic subtypes, and 17 ocular canine melanocytic neoplasms (14 melanocytomas and 3 melanomas) were used to examine and compare MCT1 expression. Immunohistochemistry using a polyclonal chicken anti-rat MCT1 antibody showed that most oral melanoma exhibited cell membrane staining, although there were no significant differences observed among the 3 histologic subtypes. In contrast, the majority of ocular melanocytic tumors were not immunoreactive. Additionally, we documented the presence of a 45-kDa band in cell membrane protein Western blots, and sequencing of a reverse transcriptase polymerase chain reaction band of expected size confirmed its identity as a partial canine MCT1 transcript in 3 oral tumors. Increased MCT1 expression in oral melanomas compared with ocular melanocytic tumors may reflect the very different biology between these tumors in dogs. These results are the first to document canine MCT1 expression in canine tumors and suggest that increased MCT1 expression may provide a potential therapeutic target for oral melanoma.

Prognostic factors (including HPV status) for irradiation of locally advanced squamous cell carcinoma of the head and neck (SCCHN)

2011 ◽  
Vol 187 (10) ◽  
pp. 626-632 ◽  
Author(s):  
Dirk Rades ◽  
Nina D. Seibold ◽  
Maximilian P. Gebhard ◽  
Frank Noack ◽  
Steven E. Schild ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Prognostic Factors ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Advanced Squamous Cell Carcinoma ◽  
Hpv Status

Longitudinal Oncology Registry of Head and Neck Carcinoma (LORHAN): Analysis of African American patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5533-5533
Author(s):  
David N. Hayes ◽  
Guangbin Peng ◽  
Eduardo Pennella ◽  
Gebra Cuyun Carter ◽  
Catherine E. Muehlenbein ◽  
...  
Keyword(s):  
African American ◽  
Head And Neck ◽  
Cox Regression ◽  
De Novo ◽  
Progression Free Survival ◽  
Head And Neck Carcinoma ◽  
Hazard Ratios ◽  
Neck Carcinoma ◽  
Hpv Status ◽  
Poor Outcomes

5533 Background: Previous retrospective analyses show poor outcomes for African American (AA) patients with head and neck carcinoma (HNC). Such racial disparities are not well understood, but patient (pt) demographics, comorbidities, tumor site, and human papillomavirus (HPV) status are suggested to play a role. Methods: The LORHAN registry was used to identify pts ≥18 yrs of age with de novo, non-metastatic HNC, and a record of survival time. This study evaluated pt and treatment characteristics by race, and conducted adjusted Cox regression analyses of overall survival (OS) and progression-free survival (PFS) to identify prognostic factors and interactions, and estimate hazard ratios (HRs) of AA vs. non-Hispanic white (NHW). Results: Baseline pt characteristics (see table below). The median OS/3-yr rate was 41.7 mo/51% in AA vs. 52.9 mo/70% in NHW, (age-adjusted HR: 1.73 [95% CI: 1.45, 2.08]). The median PFS/3-yr rate was 29.6 mo/43% in AA and 49.9 mo/62% in NHW, (age-adjusted HR: 1.64 [95%CI: 1.40, 1.93]). Multivariate analysis of OS and PFS showed that AA race, stage III and IV, PS 2, and smoking were significantly associated with a worse HR, while OP demonstrated a favorable HR over other sites. Significant interaction tests led to subgroup analyses for OS showing an elevated risk in AA with OP (HR: 2.62 [95%CI: 1.95, 3.52]) and similar risk elevations in male AA as well as in AA with PS 0-1 when compared to NHW in the corresponding subgroups. Conclusions: Controlling for other factors like PS and smoking, a worse prognosis was seen in AA males with OP localized SCCHN. Further investigation to improve the outcomes in this population is warranted. [Table: see text]

Radiographic extracapsular extension (ECE) and treatment outcomes in locally advanced oropharyngeal carcinoma (OPC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6019-6019
Author(s):  
Benjamin H. Kann ◽  
Michael Buckstein ◽  
Todd J. Carpenter ◽  
Ava Golchin ◽  
Richard Lorne Bakst ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Hazard Ratio ◽  
Smoking History ◽  
Oropharyngeal Carcinoma ◽  
Treatment Type ◽  
Hpv Status ◽  
Significant Difference

6019 Background: Pathologic ECE (pECE) of tumor through lymph node (LN) is a poor prognosticator for OPC and typically diagnosed upon surgical LN removal. At our institution, experienced radiologists routinely identify ECE on pretreatment CT. The prognostic value of radiographic ECE (rECE) is less clear and may prove clinically useful. In this study, we evaluate rECE as an independent prognosticator in OPC. Methods: Retrospective review of 185 patients with locally advanced OPC treated in our department from 2006-2012. 109 patients had accessible pretreatment CT reports clearly stating the presence or absence of rECE. Patients were treated with definitive concurrent chemoradiation therapy (CCRT) (30%), induction chemo then CCRT (47%), or surgery with adjuvant CCRT (14%) or RT (9%). Kaplan-Meier survival analysis compared these cohorts for locoregional control (LRC), distant control (DC), and progression-free (PFS) and overall survival (OS); log-rank tests were performed for significance. Multivariate analysis was conducted via cox-regression. Results: Median follow-up of the 109 patients was 31 months (range: 1-80 months). 61 patients had rECE(+) and 48 had rECE(-) scans. There was no significant difference between the cohorts in terms of median age, stage, treatment type, smoking history, or tumor HPV status. There was a difference in nodal stage with 83% of rECE(+) patients having N2-3 disease versus 67% of rECE(-) patients (p=0.02). On univariate analysis, there were differences between the rECE(-) versus rECE(+) cohorts in OS (4yr: 92% vs 72%, p=0.01), PFS (4yr: 92% vs 62%, p=0.002), and DC (4yr: 98% vs 76%, p=0.006), with no difference in LRC (4yr: 95% vs 91%, p=0.35). On multivariate analysis factoring in age, smoking history, stage, and treatment type, rECE presence was a negative predictor of OS (hazard ratio, 0.26; 95% CI, 0.07 to 0.95) and PFS (hazard ratio, 0.23; 95% CI, 0.06 to 0.81), with DC approaching significance (hazard ratio, 0.13; 95% CI, 0.02 to 1.05). Conclusions: While pECE is an established risk factor for locally advanced OPC, this study suggests that rECE may be an independent poor prognosticator of PFS, OS and DC with potential importance in guiding clinical management.

Randomised phase-III-trial of concurrent chemoradiation (CRT) for locally advanced head and neck cancer (stage III-IVB): Comparing dose reduced radiotherapy (63,6 Gy) with paclitaxel/cisplatinum to standard radiotherapy (70,6 Gy) with fluorouracil/cisplatinum.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 6016-6016 ◽  
Author(s):  
Rainer Fietkau ◽  
Heinrich Iro ◽  
Markus Hecht ◽  
Benjamin Hofner ◽  
Olaf Gefeller ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Locally Advanced ◽  
Distant Metastases ◽  
Phase Iii ◽  
Stage Iii ◽  
Advanced Head ◽  
Hpv Status ◽  
Intensified Chemotherapy

6016 Background: Concurrent CRT with 70.6 Gy is the standard treatment for locally advanced head and neck cancer (LA-SCCHN). There exist no prospective data on safety and efficacy of a reduced radiation (RT) dose. Methods: Pts with stage III-IVB LA-SCCHN were randomized 1:1 to receive 70.6 Gy with concurrent cisplatinum (20mg/m²/d IV on days 1-5 and 29-33) and fluorouracil (600 mg/m²/d CIV on days 1-5 and 29-33) (standard arm A) versus 63,6 Gy with intensified chemotherapy using concurrent cisplatinum (20mg/m²/d IV on days 1-4 and 29-32) and paclitaxel (20mg/m²/d IV on days 2, 5, 8, 11 and 25, 30, 33, 36) (experimental arm B). After a planned interim analysis recruitment was stopped due to statistical reasons. Results: Between 06/2010 and 02/2015 a total of 221 pts were randomized with 105 pts receiving treatment in arm A and 112 in arm B (4 pts dropped out). Median follow-up was 38 months. Pts’ characteristics: Oral cavity (15%), oropharynx (54%), hypopharynx (28%), larynx (14%); 17 pts had more than one primary site; tumor stage: III (14%), IV (86%); HPV-status (p16) was positive in 20%, negative in 38%, currently pending in 42%. A total of 96 PFS-related events occurred. 3-year PFS (ITT) was 58% in the standard arm A and 48% in experimental arm B (p = 0.454). 3-year OS (ITT) was 64% in arm A and 59% in arm B (p = 0.688). 3-year rates of distant metastases, loco-regional recurrences and death were 10% vs 12%, 17% vs 21% and 15% vs 19% for pts in arm A and B, respectively. As for the p16-positive subgroup, 3-year PFS/OS were 77%/76% in arm A (n = 21) and 69%/80% in arm B (n = 22), respectively. Grade 3+ hematologic adverse events during therapy (arm A/arm B): Anemia 11%/4% (p = 0.038); neutropenia 40%/16% (p < 0.001); thrombocytopenia 8%/3% (p = 0.130). Conclusions: These preliminary results indicate that pts receiving concurrent CRT for LA-SCCHN did not benefit from a lower total RT dose of 63.6Gy despite intensified chemotherapy. However, in the subgroup of p16-positive pts a reduced RT dose may be sufficiently effective. Clinical trial information: NCT01126216.

Prevalence of Fatigue in Head and Neck Cancer Survivors

2019 ◽  
Vol 128 (5) ◽  
pp. 413-419 ◽  
Author(s):  
Paolo Bossi ◽  
Patricia Di Pede ◽  
Mauro Guglielmo ◽  
Roberta Granata ◽  
Salvatore Alfieri ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Primary Tumour ◽  
Locally Advanced ◽  
Average Score ◽  
Daily Life Activities ◽  
Hpv Status ◽  
Brief Fatigue Inventory ◽  
And Gender

Introduction: In head and neck cancer (HNC) patients, fatigue is present throughout the course of treatment and during follow-up. There are limited data about the prevalence and factors associated with fatigue in HNC survivors. The objectives of this study were to assess the prevalence of fatigue and its interference with daily life activities and examine the association between fatigue and gender, age, primary tumour site, Human Papillomavirus (HPV) status, previous oncologic therapy, and time since end of treatment. Methods: Consecutive locally advanced HNC patients having completed curative treatment at least 1 year earlier and free of disease were asked to fill in the Brief Fatigue Inventory (BFI) questionnaire. Fatigue was categorized according to BFI average score as absent (0), mild (>0 to <4), moderate (≥4 to ≤6), and severe (>6 to ≤10). Results: From February 2015 to July 2016, 129 patients (median age = 60 years old; 67% male) were evaluated. Primary sites of cancer were oropharynx (46%, with 4/5 patients HPV positive), nasopharynx (22%), larynx/hypopharynx (14%), oral cavity (13%), and paranasal sinus or salivary gland (5%). Oncologic treatment was completed 12 to 96 months earlier (median = 34 months). Fatigue was reported as absent in 15% of the patients, mild in 67%, moderate in 11%, and severe in 7%. No association between BFI average score and the analyzed variables was identified. Discussion: Moderate and severe fatigue was reported in 18% of HNC survivors. Further research is needed to assess its causes and improve the management.

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