Predictive capacity of FAT1 transcriptional expression in patients with head and neck squamous cell carcinomas treated with radiotherapy.

OBJECTIVE: To analyze the predictive capacity at the primary location of the tumor of the FAT1 transcriptional expression in patients with head and neck squamous cell carcinoma treated with radiotherapy. MATERIAL AND METHODS: We conducted a retrospective study from biopsies of the primary location of the tumor in 82 patients with head and neck squamous cell carcinoma treated with radiotherapy. The transcriptional expression of FAT1 was determined by RT-PCR. The level of FAT1 transcriptional expression was categorized according to the local control after radiotherapy using a recursive partitioning analysis. RESULTS: Elevated FAT1 transcriptional expression was associated with an increased risk of local recurrence after radiotherapy. Patients with a high expression level of FAT1 (n=18; 22.0%) had a 5-year local recurrence-free survival of 42.1% (95% CI: 18.6%-65.6%), whereas for patients with a low expression (n=64; 78.0%) it was 72.4% (95% CI: 61.5%-83.3%) (p=0.002). According to the result of a multivariate analysis, patients with a high FAT1 expression category had a 2.3-fold increased risk of local recurrence (95% CI: 1.0-5.2; p=0.043). CONCLUSIONS: Elevated FAT1 transcriptional expression was associated with a significantly increased risk of local recurrence in patients with head and neck squamous cell carcinoma treated with radiotherapy.

Limitations of Molecular and Antigen Test Performance for SARS-CoV-2 in Symptomatic and Asymptomatic COVID-19 Contacts.

COVID-19 has brought unprecedented attention to the crucial role of diagnostics in pandemic control. We compared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test performance by sample type and modality in close contacts of SARS-CoV-2 cases. Close contacts of SARS-CoV-2-positive individuals were enrolled after informed consent. Clinician-collected nasopharyngeal (NP) swabs in viral transport media (VTM) were tested with a routine clinical reference nucleic acid test (NAT) and PerkinElmer real-time reverse transcription-PCR (RT-PCR) assay; positive samples were tested for infectivity using a VeroE6TMPRSS2 cell culture model. Self-collected passive drool was also tested using the PerkinElmer RT-PCR assay. For the first 4 months of study, midturbinate swabs were tested using the BD Veritor rapid antigen test. Between 17 November 2020 and 1 October 2021, 235 close contacts of SARS-CoV-2 cases were recruited, including 95 with symptoms (82% symptomatic for ≤5 days) and 140 asymptomatic individuals. Reference NATs were positive for 53 (22.6%) participants; 24/50 (48%) were culture positive. PerkinElmer testing of NP and saliva samples identified an additional 28 (11.9%) SARS-CoV-2 cases who tested negative by reference NAT. Antigen tests performed for 99 close contacts showed 83% positive percent agreement (PPA) with reference NAT among early symptomatic persons, but 18% PPA in others; antigen tests in 8 of 11 (72.7%) culture-positive participants were positive. Contacts of SARS-CoV-2 cases may be falsely negative early after contact, but more sensitive platforms may identify these cases. Repeat or serial SARS-CoV-2 testing with both antigen and molecular assays may be warranted for individuals with high pretest probability for infection.

Prognostic value of transcriptional expression of fibronectin type III domain-containing 4 (FNDC4) in head and neck carcinoma patients treated with chemoradiotherapy.

PURPOSE: FNDC4 gene encodes the fibronectin type III domain-containing 4 protein. Elevated expression of FNDC4 has been associated with poor prognosis in several types of cancer. There are no studies that have evaluated the prognostic capacity of FNDC4 in patients with head and neck cancer (HNSCC). The aim of our study was to analyze the relationship between the transcriptional expression of FNDC4 and prognosis in HNSCC patients. METHODS: We determined the transcriptional expression of FNDC4 in 67 patients with advanced-stage HNSCC (III-IV) treated with chemoradiotherapy. The FNDC4 expression was categorized according to the disease-specific survival with a recursive partitioning analysis. RESULTS: There were significant differences in disease-specific survival as a function of the level of FNDC4 transcriptional expression. The 5-year disease-specific survival for patients with high FNDC4 expression (n = 44, 65.7%) was 32.9% (95% CI: 16.5-49.3%), and for patients with low expression (n = 23, 34.3%) it was 85.4% (95% CI: 70.2-100%) (P = 0.0001). Patients with a high FNDC4 expression had poorer local (P = 0.097), regional (P = 0.008), and distant (0.034) recurrence-free survival. The results of a multivariate analysis showed that patients with a high FNDC4 expression had a 6.15-fold increased risk of death as a consequence of the HNSCC (95% CI: 1.71-22.06). CONCLUSION: FNCF4 transcriptional expression was significantly related to the disease-specific survival of HNSCC patients treated with chemoradiotherapy. Patients with elevated FNDC4 expression had a significant decrease in disease-specific survival.

Relationship between the transcriptional expression of PIM1 and local control in patients with head and neck squamous cell carcinomas treated with radiotherapy.

PURPOSE: Proviral integration site for Moloney murine leukemia virus (PIMs) are proto-oncogenes encoding serine/threonine kinases that phosphorylate a variety of substrates involved in the regulation of cellular processes. Elevated expression of PIM-1 has been associated with poor prognosis in several types of cancer. There are no studies that have analyzed the response to radiotherapy in patients with head and neck squamous cell carcinoma (HNSCC) according to the expression of PIM-1. The aim of our study was to analyze the relationship between the transcriptional expression of PIM-1 and local response to radiotherapy in HNSCC patients. METHODS: We determined the transcriptional expression of PIM-1 in 135 HNSCC patients treated with radiotherapy, including patients treated with chemoradiotherapy (n = 65) and bioradiotherapy (n = 15). RESULTS: During the follow-up, 48 patients (35.6%) had a local recurrence of the tumor. Patients with local recurrence had a higher level of PIM-1 expression than those who achieved local control of the disease (P = 0.017). Five-year local recurrence-free survival for patients with a high expression of PIM-1 (n = 43) was 44.6% (95% CI 29.2-60.0%), and for patients with low expression (n = 92) it was 71.9% (95% CI 62.5-81.3%) (P = 0.007). According to the results of multivariate analysis, patients with a high PIM-1 expression had a 2.2-fold increased risk of local recurrence (95% CI 1.22-4.10, P = 0.009). CONCLUSION: Patients with elevated transcriptional expression levels of PIM-1 had a significantly higher risk of local recurrence after radiotherapy.

Evaluating and Handling the Pain of People With Intellectual Disability.

Anecdotal reports have suggested people with intellectual disabilities experience more pain than the general population due to additional co-morbidities and secondary conditions. This multicenter comparative cross-sectional study aimed to evaluate the prevalence, factors, and treatment modalities in people with intellectual disabilities (PID) as observed by their caregivers and reported through distributed questionnaires. The study sample included 130 PID users of centers in Ciudad Real (Spain). Variables related to sociodemographic characteristics, health problems, problem behaviors, and pain were collected. Among participants, 78 (60%) of PID were males, and their mean age was 43.8 years (SD = 13.57). Pain was identified in 29 PID (22.3%; 95% confidence interval [CI] 14.99-29.81), and drugs for pain were administered to 33 PID (26.4%; 95%CI 19-34). The prevalence of pain in the sampled PID, its severity, and the analgesic administration rate were lower than those in the general population. This situation may be aggravated for PID with communication problems.

Differential Characteristics of Patients With Squamous Cell Carcinoma of the Head and Neck According to Gender.

OBJECTIVE: To analyse the trend in the percentage of patients with squamous cell carcinoma of the head and neck (SCCHN) of female gender over the last decades, and differences in survival according to gender. MATERIAL AND METHODS: Retrospective study of 5828 SCCHN diagnosed during the period 1985-2019. In the survival analysis we only included only patients with more than two years of follow-up. RESULTS: The proportion of tumours in female patients increased significantly over the study period. There was greater increase of tumours located in the oral cavity, oropharynx and larynx in the percentage of female patients. When considering the total number of patients, there were no significant differences in disease-specific survival according to gender. We observed a variable behaviour of disease-specific survival according to gender depending on the primary location of the tumour. For tumours of the larynx and oropharynx the female patients had a disease-specific survival significantly higher than that of men, while for tumours of the oral cavity, the female patients had a significant reduction of disease-specific survival. CONCLUSIONS: In our setting, the percentage of female patients with HNSCC has been increasing steadily over recent decades. There were differences in disease-specific survival according to gender depending on the location of the primary tumour.

Predictive capacity of IL-8 expression in head and neck squamous carcinoma patients treated with radiotherapy or chemoradiotherapy.

OBJECTIVE: To analyse the relationship between the transcriptional expression of interleukin-8 (IL-8) and response to treatment with radiotherapy or chemo-radiotherapy in patients with squamous cell carcinoma of the head and neck (SCCHN). MATERIAL AND METHODS: Retrospective study from tumour biopsies obtained before a treatment with radiotherapy or chemo-radiotherapy in 87 patients with SCCHN. We had a sample of healthy mucosa in 35 cases. We determined the transcriptional expression of IL-8 with RT-PCR. The transcriptional expression of IL-8 was categorized according to the local control of the disease with a recursive partitioning analysis. RESULTS: The transcriptional expression of IL-8 in tumour tissue was about 50 times higher than that in the samples of healthy mucosa. Patients with a high transcriptional expression of IL-8 (n = 56) had a 5-year local recurrence-free survival of 65.6%, and for patients with low expression (n = 31) it was 90.2% (P = 0.017). According to the results of a multivariate analysis, patients with high expression of IL-8 had a 4.1 higher risk of local recurrence of the tumour. CONCLUSIONS: SCCHN have a significant increase in transcriptional expression of IL-8 in relation to non-tumour tissue. Tumours with high IL-8 expression have an increased risk of local recurrence after treatment with radiotherapy or chemo-radiotherapy.

High-Risk Clinicopathological and Genetic Features and Outcomes in Patients Receiving Neoadjuvant Radiochemotherapy for Locally Advanced Rectal Cancer.

Administering preoperative radiochemotherapy (RCT) in stage II-III tumors to locally advanced rectal carcinoma patients has proved to be effective in a high percentage of cases. Despite this, 20-30% of patients show no response or even disease progression. At present, preoperative response is assessed by a combination of imaging and tumor regression on histopathology, but recent studies suggest that various genetic abnormalities may be associated with the sensitivity or resistance of rectal cancer tumor cells to neoadjuvant therapy. In the present study we investigated the relationship between genetic lesions detected by high-density single-nucleotide polymorphisms (SNP) arrays 6.0 and response to neoadjuvant RCT, evaluated according to Dworak criteria in 39 rectal cancer tumors before treatment. The highest frequency of copy-number (CN) losses detected corresponded to chromosomes 18q (n = 27; 69%), 1p (n = 22; 56%), 15q (n = 19; 49%), 8p (n = 18; 48%), 4q (n = 17; 46%), and 22q (n = 17; 46%); in turn, CN gains more frequently involved chromosomes 20p (n = 22; 56%), 8p (n = 20; 51%), and 15q (n = 16; 41%). There was a significant association between alterations in the 1p, 3q, 7q, 12p, 17q, 20p, and 22q chromosomal regions and the degree of response to therapy prior to surgery. However, 4q, 15q11.1, and 15q14 chromosomal region alterations were identified as important by five prediction algorithms, i.e., those with the greatest influence on predicting the tumor response to treatment with preoperative RCT. Multivariate analysis of prognostic factors showed that gains on 15q11.1 and carcinoembryonic antigen (CEA) levels serum at diagnosis were the only independent variables predicting disease-free survival (DFS). Lymph node involvement also showed a prognostic impact on overall survival (OS) in the multivariate analysis. A deep-learning-based algorithm showed a 100% success rate in predicting both DFS and OS at 60 months after diagnosis of the disease. In summary, our results indicate the existence of an association between tumor genetic abnormalities at diagnosis, response to neoadjuvant therapy, and survival of patients with locally advanced rectal cancer. In addition to the clinical and biological characteristics of locally advanced rectal cancer patients, these could be used in the future as therapeutic and prognostic biomarkers, to identify patients sensitive or resistant to preoperative treatment, helping guide therapeutic decision-making. Additional prospective studies in larger series of patients are required to confirm the clinical utility of the newly identified biomarkers.

Head and neck squamous cell carcinoma in cigar smokers. Distinctive epidemiological and prognostic characteristics.

OBJECTIVE: The objective of this study is to assess the existence of differences in the epidemiological characteristics and prognosis of patients with head and neck squamous cell carcinoma (HNSCC) who smoke cigars. MATERIAL AND METHODS: We carried out a retrospective study of a cohort of 4500 patients with HNSCC treated during the period 1985-2017. RESULT: The proportion of cigar smokers was 2.4%, compared with 88.3% of cigarette smokers and 9.3% of non-smokers. There was an increase in the proportion of cigar smokers throughout the study period. With respect to cigarette smokers, cigar smokers had a higher proportion of male patients, a higher average age at diagnosis, and they had a higher frequency of tumours located in the oral cavity and hypopharynx. The results of a univariate analysis showed that the disease-specific survival of cigar smokers was lower than that of the other patients. Five-year disease-specific survival of cigar smokers was 60.9%, compared to 69.0% for non-smokers, 72.8% for smokers of less than 20 cigarettes/day, and 67.2% for smokers of more than 20 cigarettes/day. There were differences in the pattern of survival depending on tobacco consumption based on the location of the primary tumour. CONCLUSIONS: A 2.4% of patients with HNSCC had a history of regular consumption of cigars. Disease-specific survival of cigar smokers was lower than that of other patients.

Tracking the Antibody Immunome in Sporadic Colorectal Cancer by Using Antigen Self-Assembled Protein Arrays.

Sporadic Colorectal Cancer (sCRC) is the third leading cause of cancer death in the Western world, and the sCRC patients presenting with synchronic metastasis have the poorest prognosis. Genetic alterations accumulated in sCRC tumor cells translate into mutated proteins and/or abnormal protein expression levels, which contribute to the development of sCRC. Then, the tumor-associated proteins (TAAs) might induce the production of auto-antibodies (aAb) via humoral immune response. Here, Nucleic Acid Programmable Protein Arrays (NAPPArray) are employed to identify aAb in plasma samples from a set of 50 sCRC patients compared to seven healthy donors. Our goal was to establish a systematic workflow based on NAPPArray to define differential aAb profiles between healthy individuals and sCRC patients as well as between non-metastatic (n = 38) and metastatic (n = 12) sCRC, in order to gain insight into the role of the humoral immune system in controlling the development and progression of sCRC. Our results showed aAb profile based on 141 TAA including TAAs associated with biological cellular processes altered in genesis and progress of sCRC (e.g., FSCN1, VTI2 and RPS28) that discriminated healthy donors vs. sCRC patients. In addition, the potential capacity of discrimination (between non-metastatic vs. metastatic sCRC) of 7 TAAs (USP5, ML4, MARCKSL1, CKMT1B, HMOX2, VTI2, TP53) have been analyzed individually in an independent cohort of sCRC patients, where two of them (VTI2 and TP53) were validated (AUC ~75%). In turn, these findings provided novel insights into the immunome of sCRC, in combination with transcriptomics profiles and protein antigenicity characterizations, wich might lead to the identification of novel sCRC biomarkers that might be of clinical utility for early diagnosis of the tumor. These results explore the immunomic analysis as potent source for biomarkers with diagnostic and prognostic value in CRC. Additional prospective studies in larger series of patients are required to confirm the clinical utility of these novel sCRC immunomic biomarkers.

Differential characteristics of patients with squamous cell carcinoma of the head and neck according to gender. / Características diferenciales de los pacientes con carcinomas escamosos de cabeza y cuello en función del género.

OBJECTIVE: To analyse the trend in the percentage of patients with squamous cell carcinoma of the head and neck of female gender over the last decades, and differences in survival according to gender. MATERIAL AND METHODS: Retrospective study of 5,828 squamous cell carcinoma of the head and neck diagnosed during the period 1985-2019. In the survival analysis we only included only patients with more than two years of follow-up. RESULTS: The proportion of tumours in female patients increased significantly over the study period. There was greater increase of tumours located in the oral cavity, oropharynx and larynx in the percentage of female patients. When considering the total number of patients, there were no significant differences in disease-specific survival according to gender. We observed a variable behaviour of disease-specific survival according to gender depending on the primary location of the tumour. For tumours of the larynx and oropharynx the female patients had a disease-specific survival significantly higher than that of men, while for tumours of the oral cavity, the female patients had a significant reduction of disease-specific survival. CONCLUSIONS: In our setting, the percentage of female patients with squamous cell carcinoma of the head and neck has been increasing steadily over recent decades. There were differences in disease-specific survival according to gender depending on the location of the primary tumour.

Organ preservation in patients with advanced laryngeal tumours. Results of induction chemotherapy versus chemoradiotherapy in actual clinical practice. / Preservación de órgano en pacientes con tumores avanzados de laringe. Resultados de la quimioterapia de inducción versus quimio-radioterapia en la práctica clínica real.

INTRODUCTION AND OBJECTIVES: A high percentage of patients with locally advanced larynx carcinomas are candidates for inclusion in organ preservation protocols. The objective of this study is to compare the results of two schemes of preservation, induction chemotherapy versus chemoradiotherapy, in patients with locally advanced larynx carcinomas in the context of actual clinical practice. METHODS: Our retrospective study included 157 patients with locally advanced tumours of the larynx (T3-T4) treated with induction chemotherapy (n = 121) or chemoradiotherapy (n = 36). RESULTS: From 121 patients who began treatment with induction chemotherapy, 6 died due to toxicity, 37 were treated with surgery, and 78 completed the preservation scheme; 36 patients received treatment with chemoradiotherapy. There were no significant differences in 5-year disease-specific survival between both treatments: 68.9% in induction chemotherapy versus 75.7% in chemoradiotherapy (p = 0.259). In 45.9% of patients the laryngeal function was preserved. Patients treated with chemoradiotherapy had a tendency to have better 5-year laryngeal dysfunction-free survival than patients treated with induction chemotherapy (55.6% versus 44.8%, p = 0.079). CONCLUSION: Patients included in a protocol of organ preservation achieved a 5-year laryngeal dysfunction-free survival of 45.9%. There were no significant differences in disease-specific survival among patients treated with induction chemotherapy or chemoradiotherapy.

Organ preservation after treatment with induction chemotherapy in patients with locally advanced carcinomas (T3-T4) of oral cavity and oropharynx. / Preservación de órgano tras un tratamiento con quimioterapia de inducción en pacientes con carcinomas localmente avanzados (T3-T4) de cavidad oral y orofaringe.

INTRODUCTION AND OBJECTIVES: With the goal of achieving functional preservation, one of the treatment strategies for patients with locally advanced squamous cell carcinomas of the head and neck is to initiate treatment with induction chemotherapy (CT) and decide the second therapeutic manoeuvre depending on the response. The objective of this study is to evaluate organ preservation capacity based on this therapeutic approach in patients with tumours of the oral cavity and oropharynx. METHODS: A retrospective study of 246 patients with locally advanced carcinomas of the oral cavity or oropharynx (cT3-T4) initially treated with induction CT. RESULTS: After induction CT 28% of patients achieved a complete response of the primary location of the tumour, 43.1% a partial response greater than 50%, and 28.9% a reduction less than 50% or persistence. After the induction CT treatment 70 patients (28.5%) underwent surgical treatment, and 176 (71.5%) radiotherapy (RT) or chemoradiotherapy (CRT). Considering the patients treated non-surgically (n=176), organ preservation for patients with a complete response (n=66) was 65.2%, for those patients with a partial response greater than 50% (n=75) it was 30.7%, and for patients with a partial response less than 50% or persistence (n=35) it was 14.3%. CONCLUSION: The response to treatment with induction CT has prognostic value in patients with locally advanced carcinomas of the oral cavity and oropharynx. Patients who are candidates for conservative treatment with RT or CRT would be those who achieve a complete response after induction treatment.

Oncological results of salvage treatment in patients with hypopharyngeal carcinoma. / Resultados oncológicos del tratamiento de rescate en pacientes con carcinomas de hipofaringe.

INTRODUCTION AND OBJECTIVE: The aim of this study is to analyse the variables related to the feasibility of salvage surgery with radical intention in patients with a local recurrence of hypopharyngeal carcinoma, and to evaluate the oncological performance of this type of surgery. METHODS: Retrospective study of 96 patients with hypopharyngeal carcinoma with local tumour recurrence RESULT: Only 27 patients (28.1%) were considered for surgical salvage treatment. The variables related to feasibility of salvage surgery were non-surgical initial treatment of the tumour and a disease-free interval greater than 6 months. All 69 patients non-candidates for salvage surgery died as a result of tumour progression in a period of less than 2.5 years. The 5-year disease-specific survival rate for the patients treated with salvage surgery was 39.5%. The only variable significantly related to disease-specific survival was the status of the resection margins. Patients with extensive tumour recurrence (rT3-T4) or with simultaneous nodal involvement had a lower survival rate, but the differences did not reach statistical significance. CONCLUSION: Only 28% of the patients with hypopharyngeal carcinoma with local recurrence of the tumour were eligible for salvage surgery with radical intention. The patients treated with salvage surgery had a 5 -year disease-specific survival of 39.5%.

Predictive capacity of IL-8 expression in head and neck squamous carcinoma patients treated with radiotherapy or chemoradiotherapy. / Capacidad predictiva de la expresión de IL-8 en pacientes con carcinomas escamosos de cabeza y cuello tratados con radioterapia o quimio-radioterapia.

OBJECTIVE: To analyse the relationship between the transcriptional expression of interleukin-8 (IL-8) and response to treatment with radiotherapy or chemo-radiotherapy in patients with squamous cell carcinoma of the head and neck (SCCHN). MATERIAL AND METHODS: Retrospective study from tumour biopsies obtained before a treatment with radiotherapy or chemo-radiotherapy in 87 patients with SCCHN. We had a sample of healthy mucosa in 35 cases. We determined the transcriptional expression of IL-8 with RT-PCR. The transcriptional expression of IL-8 was categorized according to the local control of the disease with a recursive partitioning analysis. RESULTS: The transcriptional expression of IL-8 in tumour tissue was about 50 times higher than that in the samples of healthy mucosa. Patients with a high transcriptional expression of IL-8 (n=56) had a 5-year local recurrence-free survival of 65.6%, and for patients with low expression (n=31) it was 90.2% (P=.017). According to the results of a multivariate analysis, patients with high expression of IL-8 had a 4.1 higher risk of local recurrence of the tumour. CONCLUSIONS: SCCHN have a significant increase in transcriptional expression of IL-8 in relation to non-tumour tissue. Tumours with high IL-8 expression have an increased risk of local recurrence after treatment with radiotherapy or chemo-radiotherapy.

Prognostic capacity of the lymph node ratio in squamous cell carcinomas of the head and neck. / Capacidad pronóstica de la densidad ganglionar en los carcinomas escamosos de cabeza y cuello.

INTRODUCTION AND OBJECTIVES: Lymph node density or lymph node ratio (LNR), defined as the quotient between the total number of positive lymph nodes and the total number of dissected lymph nodes, has demonstrated a prognostic capacity in several tumour models, including patients with head and neck squamous cell carcinomas (HNSCC). The aim of the present study is to analyse the prognostic value of LNR in a wide cohort of patients with HNSCC. METHODS: We carried out a retrospective study of a cohort of 1,311 patients with HNSCC treated with unilateral or bilateral neck dissections. Of the patients included in the study, 55.0% had lymph node metastases (pN+). We proceeded to calculate the value of the LNR, and its categorization through a recursive partition analysis considering specific survival as the dependent variable. RESULTS: Three categories were defined according to the value of the LNR with a cut-off point at the values < of .025 and .118. The 5-year specific survival for patients with an LNR less than .025 (n=654, 49.8%) was 87.2%, for patients with a LNR .025-.118 (n=394, 30.1%) it was 51.6%, and for patients with a LNR greater than .188 (n=263, 20.1%) it was 27.3% (P=.0001). According to the results of a multivariate analysis, the LNR significantly related to specific survival. CONCLUSION: The LNR can be a prognostic variable to be considered in the pathological staging of the lymph nodes.

Weighted lymph node ratio: New tool in the assessment of postoperative staging of the neck dissection in HPV-negative head and neck squamous cell carcinoma patients.

BACKGOUND: The objective of this study is to assess a new parameter, the weighted lymph node ratio (WLNR), which incorporates prognostic information regarding the number of metastatic nodes with extracapsular spread and the lymph node yield for pN0 patients to the lymph node ratio. METHODS: We studied retrospectively 1118 patients with head and neck squamous cell carcinoma (HNSCC) treated with a neck dissection. RESULTS: We obtained a classification with four categories based on the WLNR values. WLNR classification had a higher prognostic discrimination capacity and a more homogeneous distribution in the number of patients included in each of the categories than the pTNM classification. CONCLUSION: The WLNR improved the predictive capacity of the eighth edition of the pTNM classification and it can be a useful tool in the assessment of the postoperative staging of the neck dissections in HNSCC patients.

Prognostic implications of EGFR protein expression in sporadic colorectal tumors: Correlation with copy number status, mRNA levels and miRNA regulation.

Sporadic colorectal cancer (sCRC) is the third most frequent cancer worldwide and the second most common cause of cancer-related deaths (mainly due metastatic dissemination). We investigated the immunohistochemical expression of frequently altered proteins in primary tumors from 51 patients (25 liver metastatic and 26 non-metastatic cases) with a median 103 months follow-up (103 months). We evaluated EGFR copy number (using SNP arrays and FISH) and its expression and regulation (by mRNA and miRNA arrays). We found differences between metastatic and non-metastatic sCRCs for MLH1 (p = 0.05), PMS2 (p = 0.02), CEA (p < 0.001) and EGFR (p < 0.001) expression. EGFR expression was associated with lymph node metastases (p = 0.001), liver metastases at diagnosis (p < 0.001), and advanced stage (p < 0.001). There were associations between EGFR expression-, EGFR gene copy number- and EGFR mRNA levels. We found potential interactions of two miRNAs targeting EGFR expression, (miR-134 and miR-4328, in non-metastatic and metastatic tumors, respectively). EGFR expression was associated with a worse outcome (p = 0.005). Multivariate analysis of prognostic factors for overall survival identified that, the expression of EGFR expression (p = 0.047) and pTNM stage (p < 0.001) predicted an adverse outcome. EGFR expression could be regulated by amplification or polysomies (in metastatic tumors), or miRNAs (miRNA-134, in non-metastatic tumors). EGFR expression in sCRC appears to be related to metastases and poor outcome.

Does age influence disease-specific survival in patients with squamous cell carcinomas of the head and neck?

BACKGROUND AND OBJECTIVES: The number of patients diagnosed with head and neck squamous cell carcinoma (HNSCC) at an advanced age has increased. The aim of this study is to evaluate the age at which disease-specific survival (DSS) significantly decreases in HNSCC. METHODS: We performed a retrospective study of 5469 patients with HNSCC treated at our center (1985-2016). External validation with 2082 oral squamous cell carcinomas from a collaborative institution from another continent was performed. RESULTS: We observed an orderly decrease in overall survival as age at diagnosis increased. There were no differences in DSS based on age for patients <80 years old (P = .623), while older patients had a significant decrease in DSS. These results were validated in the independent dataset. In a multivariable analysis performed in the test set, compared to patients <80 years old, patients between 80 to 85 had a 1.50 times higher risk of disease-specific death (95% confidence interval [CI]: 1.19-1.89; P = .001), and patients >85 had a 2.19 times higher risk (95% CI: 1.68-2.87; P < .001). CONCLUSIONS: DSS started to significantly decrease in HNSCC at 80 years old. These findings, validated in an independent cohort, indicate that chronological age on its own should not withhold curative treatment in the majority of patients with HNSCC.