Clinicopathological characteristics and prognosis of brain metastases in elderly patients with esophageal carcinoma.

BACKGROUND: Brain metastases (BM) from esophageal carcinoma (EC) is clinically rare and has not yet been reported in elderly patients. This study aimed to investigate the clinicopathological characteristics, outcomes and prognostic factors of BM in elderly patients with EC, in order to provide guidance for clinical practice. METHODS: A total of 20 EC patients older than 65 years who were diagnosed with BM were identified from the fourth Hospital of Hebei Medical University between January 1, 2009 and December 31, 2018. Survival was evaluated by the Kaplan-Meier method and Cox proportional hazards models. RESULTS: The median time from diagnosis of EC to BM was 11.8 months (0-249.2 months). The median overall survival (OS) was 4.8 months (1.13-23.3 months), with 20% of patients achieving the 1-year survival rate. Patients with KPS score of ≥70 had a significantly better OS than those with KPS score<70 (8.4 vs. 3.9 months, p = 0.033). Compared to patients without brain radiotherapy, patients with brain radiotherapy showed better outcomes in both median OS (8.4 vs. 2.9 months) and 1-year survival rate (23.1% vs. 14.3%, p = 0.043). The median OS of patients with radiotherapy combined with chemotherapy and/or targeted therapy and radiotherapy alone was 9.7 months (3.4-23.3 months) and 7.2 months (1.7-18.4 months), respectively, with no significant difference between the two groups (p = 0.215). CONCLUSIONS: Brain radiotherapy provided clinically meaningful survival benefit for elderly patients with BM from EC. Thus, active treatments for those patients might be required.

A systematic review and meta-analysis of the prognostic role of age in oral tongue cancer.

While evidence suggests an increasing incidence of tongue cancer in young adults, published findings regarding the prognostic role of age at diagnosis are inconsistent. We performed a meta-analysis of the literature to highlight key points that might help in understanding the association between age of oral tongue cancer patients at diagnosis and their prognosis. According to age at diagnosis, a systematic literature review of all published cohort studies assessing the recurrence risks and mortality associated with tongue cancer was conducted. We compared the risk estimates between patients aged >45 years and those aged <45 years at diagnosis. Random-effects models were used to calculate summary relative risk estimates (SRRs) according to different clinical outcomes and sources of between-study heterogeneity (I2 ) and bias. We included 31 independent cohort studies published between 1989 and 2019; these studies included a total of 28,288 patients. When risk estimations were not adjusted for confounders, no significant association was found between age at diagnosis and overall survival (OS). Conversely, after adjustment for confounders, older age at diagnosis was associated with a significantly increased risk of mortality. The difference between SRRs for adjusted and unadjusted estimates was significant (p < 0.01). Younger patients had a significantly higher risk of local recurrence. Younger patients with oral tongue cancer have better OS but a greater risk of recurrence than older patients. These findings should be validated in a large prospective cohort study which considers all confounders and prognostic factors.

Estimación del efecto en el tamaño y la supervivencia de los tumores cutáneos debido al confinamiento por COVID-19: Modelo basado en un crecimiento exponencial / Estimated Effect of COVID-19 Lockdown on Skin Tumor Size and Survival: AnExponential Growth Model

BACKGROUND AND OBJECTIVES: Spain is in a situation of indefinite lockdown due to the ongoing coronavirus disease 2019 (COVID-19) pandemic. One of the consequences of this lockdown is delays in medical and surgical procedures for common diseases. The aim of this study was to model the impact on survival of tumor growth caused by such delays in patients with squamous cell carcinoma (SCC) and melanoma. MATERIAL AND METHODS: Multicenter, retrospective, observational cohort study. We constructed an exponential growth model for both SCC and melanoma to estimate tumor growth between patient-reported onset and surgical excision at different time points. RESULTS: Data from 200 patients with SCC of the head and neck and 1000 patients with cutaneous melanoma were included. An exponential growth curve was calculated for each tumor type and we estimated tumor size after 1, 2, and 3 months of potential surgical delay. The proportion of patients with T3 SCC (diameter > 4 cm or thickness > 6 mm) increased from 41.5% (83 patients) in the initial study group to an estimated 58.5%, 70.5%, and 72% after 1, 2, and 3 months of delay. Disease-specific survival at 2, 5, and 10 years in patients whose surgery was delayed by 3 months decreased by 6.2%, 8.2%, and 5.2%, respectively. The proportion of patients with ultrathick melanoma (> 6 mm) increased from 6.9% in the initial study group to 21.9%, 30.2%, and 30.2% at 1, 2, and 3 months. Five-and 10-year disease-specific survival both decreased by 14.4% in patients treated after a potential delay of 3 months. CONCLUSIONS: In the absence of adequate diagnosis and treatment of SCC and melanoma in the current lockdown situation in Spain, we can expect tosee to a considerable increase in large and thick SCCs and melanomas. Efforts must be taken to encourage self-examination and facilitate access to dermatologists in order to prevent further delays

ANTECEDENTES Y OBJETIVOS: La pandemia del coronavirus COVID-19 ha provocado un confinamiento indefinido. Una posible consecuencia de esta situación es un retraso en los procedimientos asistenciales de las patologías comunes. El objetivo de este estudio es estimar el hipotético impacto en la supervivencia que tendría el aumento del tamaño tanto para los carcinomas de células escamosas (CCE) como de los melanomas. MATERIAL Y MÉTODO: Estudio observacional retrospectivo de cohortes multicéntrico. Se desarrolló un modelo de crecimiento exponencial para cada tumor basado en el tiempo de evolución que refiere el paciente. RESULTADOS: Se incluyeron un total de 200 pacientes con CCEs localizados en la cabeza y el cuello y 1000 pacientes con melanoma cutáneo. Se calculó una curva de crecimiento exponencial para cada tumor y se estimó el tamaño del tumor tras 1, 2 y 3 mes tras el diagnóstico. En la muestra, los CCE mayores de 4 cm o > 6 mm de grosor (definidos como T3) pasaron de 83 (41.5%) en el grupo de estudio real a una estimación de 58,5%, 70,5% y 72% tras 1, 2 y 3 meses de retraso quirúrgico estimado. Se estimó una disminución de la supervivencia específica de enfermedad (SEE) de un 6,2%, 8,2% y 5,2% a los 2, 5 y 10 años, respectivamente, tras tres meses de retraso. Para los melanomas, los melanomas ultragruesos (> 6 mm) pasaron del 6,9% en el grupo de estudio al 21,9%, 30,2% y 30,2% tras 1,2 y 3 meses de demora. La SEE a los 5 y 10 años del grupo de estudio descendió un 14,4% en ambos tiempos. CONCLUSIONES: En ausencia de un adecuado diagnóstico y tratamiento de los pacientes con CCE y melanoma en la actual situación de confinamiento en España, podemos llegar a asistir a un considerable aumento de los casos de CCE y melanomas gruesos y de gran tamaño. Se deben fomentar los esfuerzos para promocionar la autoexploración y facilitar el acceso a los dermatólogos para no aumentar la demora de estos pacientes. Palabras clave: melanoma, pronóstico, diagnóstico precoz, carcinoma de células escamosas cutáneo, COVID-19, confinamiento

The role of bile reflux and its related NF-κB activated pathway in progression of hypopharyngeal squamous cell cancer.

BACKGROUND: Prognosis for hypopharyngeal cancer is usually poor, and recurrence is common. Identifying new factors or related mechanisms that promote its progression may have clinical implications. Although, recent studies support bile reflux in hypopharyngeal carcinogenesis, it remains to be explored how bile and its related NF-κB activated pathway may further affects its progression in already established hypopharyngeal cancer. METHODS: Hypopharyngeal squamous cell carcinoma (HSCC) cell lines, FaDu and UMSCC11A, both negative for HPV, were repetitively exposed to bile acids (400 µM) at variable pH points (4.0, 5.5 and 7.0). Immunofluorescence, western blotting, luciferase assay, and qPCR were used to detect NF-κB activation, bcl-2 overexpression and gene expression. RESULTS: Bile at strongly acidic pH (4.0) potentiated the activation of NF-κB and its related mRNA phenotype in HSCC cells. IL-6, TNF-α, and BCL2 were found among the highest overexpressed genes as was previously found in HSCCs excised from patients with documented biliary reflux. An enhanced transcriptional activity of EGFR, RELA, STAT3, and WNT5Α and higher survival rates were observed in HSCC cells exposed to acidic bile compared to those exposed to bile at weakly acidic or neutral pH. CONCLUSION: Our novel findings support the observation that bile reflux has the potential for actively influencing the progression of hypopharyngeal cancer, mediated by NF-κB. In patients with hypopharyngeal cancer and known gastroesophageal reflux disease, antacid therapy may exert a role in furthering control of disease recurrence and progression.

The effect of lymph node metastasis on overall survival and disease-free survival in vulvar cancer patients.

OBJECTIVES: To examine the effect of lymphadenectomy on survival in patients with squamous cell vulvar carcinoma. MATERIAL AND METHODS: Patients with squamous cell vulvar cancer who underwent surgery were retrospectively analyzed. All procedures were performed according to current recommendations/standard of treatment. The clinical and pathological features were examined. Sixty-eight patients were studied. The mean age was 64.7 ± 10.9 years. Twenty-three (33.8%) patients had nodal metastasis. Most patients (60.3%) were in stage IB. Adjuvant radiotherapy and chemo-radiotherapy were administered to 33.8% and 25% of the patients, respectively. The median follow-up time was 28.5 (4-183) months. Recurrence occurred in 18 (26.5%) cases. RESULTS: There was no significant difference between node-positive and node-negative patients in terms of age, number of dissected lymph nodes and recurrence. Tumor diameter was significantly higher in the metastatic group. Age and surgical margin positivity were independent prognostic factors for overall survival (OS). Surgical margin positivity and lymph node metastasis had no effect on disease-free survival (DFS). CONCLUSIONS: Our results showed that age and surgical margin positivity were independent prognostic factors for OS. Although surgical margin positivity increased the risk of recurrence in univariate analysis, it was not a significant factor affecting DFS. OS was significantly lower in patients with lymph node metastasis.

The efficacy of PD-1/PD-L1 inhibitors in advanced squamous-cell lung cancer: a meta-analysis of 3112 patients.

Aim: We performed a meta-analysis to explore the efficacy of immunotherapy for patients with squamous non-small-cell lung cancer (NSCLC). Materials & methods: Randomized clinical trials comparing immunotherapy with chemotherapy for advanced NSCLC patients were included. Results: A total of 11 trials (3112 patients) were included. PD-1/PD-L1 inhibitors demonstrated significant superiority to chemotherapy in overall survival (OS) (hazard ratio [HR]: 0.74; p < 0.001) and progression-free survival (PFS) (HR: 0.66; p < 0.001) for squamous NSCLC. The OS and PFS benefits of PD-1/PD-L1 inhibitors for squamous NSCLC were similar in subgroup analyses of line settings, PD-L1 expression and different study methodologies. No advantage in OS was found in advanced squamous NSCLC patients treated with atezolizumab (HR: 0.87; p = 0.087). Conclusion: PD-1/PD-L1 inhibitors significantly improved OS and PFS in advanced squamous NSCLC patients when compared with chemotherapy.

Prognostic value of posttreatment HPV-specific antibodies in patients with oropharyngeal tumors.

BACKGROUND: The presence of human papillomavirus (HPV)-specific antibodies in patients with head and neck cancer at enrollment has prognostic significance. In cervical carcinoma patients, the decrease of HPV E6/E7-specific antibodies appears to be associated with a better prognosis. METHODS: This prospective study with follow-up focused on the persistence and prognostic value of antibodies specific for HR HPV-derived VLPs and HPV16 E6/E7 oncoproteins in patients with oropharyngeal cancers. In this study, we analyzed sera of 93 patients taken a year after the end of treatment and sera from 58 of these patients taken up to 14 years after treatment. RESULTS: The level of HPV-specific antibodies decreased on the 1-year follow-up and the decrease during the long follow-up was statistically significant. For HPV16 E7 antibodies the decrease was steeper in nonrecurrent patients. While the level of antibodies at enrollment was not predictive of recurrences, the decrease of HPV16 E6 antibodies at 1-year follow up was associated with better overall as well as disease-specific survival of patients. CONCLUSIONS: The data suggest that the pretreatment level of HPV-specific antibodies is not predictive of the occurrence of recurrences but the decrease HPV16 E6 antibodies on the 1-year follow-up is predictive of better survival of HN patients.

Long noncoding antisense RNA FAM83A-AS1 promotes lung cancer cell progression by increasing FAM83A.

The abnormal expression of long noncoding RNAs (lncRNAs) is closely associated with human cancers. As one special group of lncRNAs, natural antisense transcripts (NATs) can be transcribed from both DNA strands at the same locus but in the opposite direction from the gene transcript. Their expression levels are altered in many cancers, but their roles are poorly understood. We strove to find NATs involved in human non-small-cell lung cancer (NSCLC) and to reveal their mechanism of action in cancer. We analysed the NATs in NSCLC from the TCGA database by circlncRNAnet. One NAT, family with sequence similarity 83 member A antisense RNA 1 (FAM83A-AS1), was found to be markedly upregulated and positively correlated with its cognate sense counterpart, FAM83A, in NSCLC. Moreover, overexpression of FAM83A-AS1 increased FAM38A protein levels and induced ERK1/2 phosphorylation downstream of FAM83A in cells. Finally, overexpression of FAM83A-AS1 promoted LUAD cell proliferation and invasion. In summary, lncRNA FAM83A-AS1 promotes LUAD by increasing FAM83A expression.

Fibroblast growth factor receptor 1 and 3 expression is associated with regulatory PI3K/AKT kinase activity, as well as invasion and prognosis, in human laryngeal cancer.

PURPOSE: Aberrant fibroblast growth factor receptor (FGFR) expression is thought to contribute to the development of many types of cancer. As yet, however, their impact on the course and prognosis of head and neck cancer remains to be determined. Here, we aimed to investigate the effects of expression of the FGFR family members FGFR1 and FGFR3, as well as their downstream PI3K/AKT signal-regulated kinases, on the aggressiveness and prognosis of laryngeal cancer. METHODS: In total 137 surgically removed squamous cell laryngeal cancer (SCLC) and 100 matched non-cancerous laryngeal mucosa (NCLM) samples were assessed for mRNA expression using quantitative real-time PCR. The corresponding proteins were analyzed by Western blotting. SLUG expression was assessed by immunohistochemistry. The expression data were subsequently related to tumor front grading (TFG), local/nodal recurrences, prognosis and overall survival. RESULTS: The FGFR1, FGFR3 and PI3K/AKT kinase mRNA and protein levels were found to be significantly higher in the SCLC than the NCLM samples (p < 0.05). A high FGFR1 mRNA/protein expression level was found to be associated with an increased invasion rate, according to TFG scale and SLUG level, a high local/nodal recurrence rate and a poor prognosis (p < 0.05). Similarly, we found that a high FGFR3 mRNA/protein expression level was associated with a shorter survival time (p < 0.05). In addition, we found that high PI3K/AKT kinase mRNA/protein levels were associated with a high TFG (p < 0.05). We also found that FGFR1/3 mRNA and FGFR1 protein levels were inversely associated with overall survival (log-rank test: FGFR1 mRNA p = 0.03, FGFR3 mRNA p = 0.04, FGFR1 protein p = 0.03). Subsequent multivariate analyses revealed that high FGFR3 mRNA expression may serve as an independent poor prognostic factor (HR 2.32, 95% CI 1.03-6.59; p = 0.04). We also found that the p-PI3K regulatory kinase protein level was significantly associated with survival in the cohort studied (HR 1.78, 95% CI 0.64-8.53; p = 0.03). CONCLUSIONS: From our data we conclude that FGFR1 and FGFR3, as well as its downstream regulatory PI3K/AKT kinases, may serve as potential biomarkers for the invasiveness and prognosis of laryngeal cancer. The expression of FGFR1/3-PI3K/AKT regulatory pathway members may be instrumental for the identification of patients at risk for an unfavorable clinical outcome.

Association of Metformin Use and Survival Outcome in Women With Cervical Cancer.

OBJECTIVE: Although preclinical studies suggest possible antitumor effects of metformin against cervical cancer, there is currently a lack of clinical data examining the association of metformin use and survival in women with cervical cancer. The aim of this study was to examine survival of women with cervical cancer who were receiving metformin. METHODS: This is a retrospective study examining consecutive cases of stages I to IV cervical cancer between 2000 and 2014. Patient demographics, medication use, tumor characteristics, treatment patterns, and survival outcomes were correlated to metformin use. RESULTS: There were 70 (8.9%; 95% confidence interval [CI], 6.9-10.9) metformin users and 715 nonusers identified for the analysis. Median follow-up time was 22.6 months. Recurrence/progression of disease and death due to cervical cancer were observed in 236 and 163 cases, respectively. Metformin users were more likely to be older, hypertensive, diabetic, and dyslipidemic compared with nonusers (all, P < 0.05). On univariate analysis, metformin users and nonusers had similar progression-free survival (PFS) (5-year rates; 57.3% vs 61.8%; P = 0.82) and cervical cancer-specific overall survival (71.7% vs 70.7%; P = 0.86). After adjusting for patient demographics and tumor characteristics, metformin use was not associated with PFS (adjusted hazards ratio, 1.11; 95% CI, 0.70-1.74; P = 0.67) or cervical cancer-specific overall survival (adjusted hazards ratio, 0.91; 95% CI, 0.52-1.60; P = 0.75). Among 478 women who received whole pelvic radiotherapy, metformin use was not associated with PFS (P = 0.93) or cervical cancer-specific overall survival (P = 0.32). CONCLUSIONS: In this study population, metformin use was not associated with survival of women with cervical cancer.

Impact of pre-operative body mass index in head and neck cancer patients undergoing microvascular reconstruction.

OBJECTIVES: To analyse the relationship of pre-operative body mass index with surgical complications and oncological outcomes in patients undergoing microvascular reconstruction for head and neck squamous cell cancer. METHOD: A retrospective review was conducted of 259 patients who underwent microvascular free flap reconstruction after head and neck ablative surgery. RESULTS: Mean body mass index was 22.48 kg/m2. There were no correlations between body mass index and: flap failure (p = 0.739), flap ischaemia (p = 0.644), pharyngocutaneous fistula (p = 0.141) or wound infection (p = 0.224). The five-year disease-specific survival rate was 63 per cent. On univariate analysis, the five-year disease-specific survival rate was significantly correlated with pre-operative body mass index, based on Kaplan-Meier survival curves (p = 0.028). The five-year disease-specific survival rates in underweight, normal weight, overweight and obese groups were 47 per cent, 55 per cent, 65 per cent and 80 per cent, respectively. CONCLUSION: Pre-operative body mass index was a useful predictor for recurrence and survival in patients who underwent microvascular reconstruction for head and neck squamous cell cancer.

Multicenter Phase II Study of Panitumumab in Platinum Pretreated, Advanced Head and Neck Squamous Cell Cancer.

LESSONS LEARNED: Panitumumab shows activity in terms of disease control rate and preventing disease progression but not for tumor shrinkage in head and neck squamous cell cancer for second-line treatment. Epidermal growth factor receptor (EGFR) copy number gain, a property of tumor cells that theoretically could identify patients more likely to experience disease response, was common among patients having disease control.Our trial, given the lower toxicity with an every-2-week schedule, provides guidance for future trials, for example, in combinations of immune therapies and anti-EGFR-antibodies. BACKGROUND: The objective of this study was to investigate the efficacy and safety of panitumumab (anti-epidermal growth factor receptor [EGFR] antibody) given as a single agent in platinum-pretreated head and neck squamous cell cancer (HNSCC). METHODS: Patients with advanced HNSCC previously treated with platinum-containing therapy were included. Panitumumab was administered intravenously every 2 weeks at a dose of 6 mg/kg. Primary endpoint was overall response rate (ORR) according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1; secondary endpoints were progression-free survival (PFS) and safety. A Simon's two-step design was chosen; 4 partial remissions (PR) in the first 32 patients were required for continuing to step two. An exploratory biomarker analysis was performed. RESULTS: Thirty-three patients were enrolled. Two patients obtained a PR for an ORR of 6%, and 15 (45%) showed stable disease (SD) for at least 2 months, resulting in a 51% disease control rate. Median PFS was 2.6 months (95% confidence interval [CI]: 1.7-3.7), while median OS was 9.7 months (95% CI: 6.3-17.2). The most frequent adverse drug reactions were cutaneous rash (64%) and hypomagnesemia (55%). Overall, 30% of patients experienced grade 3/4 adverse events. No infusion-related reactions occurred. EGFR copy number gain (CNG) was more frequent in patients who benefitted from panitumumab. Two uncommon KRAS mutations (G48E, T50I) and 3 canonical PIK3CA mutations (all E545K) were detected. High-risk HPV16 was found in 10 patients and EGFR CNG in 13 treated patients. EGFR CNG seems to be more frequent in individuals with at least SD compared with patients with progressive disease (59% vs. 30%). PFS for patients with EGFR CNG was 4.6 months (95% CI: 1.0-9.2 months) and 1.9 months (95% CI: 1.0-3.2 months) for patients without CNG (p = .02). CONCLUSION: Panitumumab monotherapy in pretreated HNSCC patients was well tolerated but moderately active. We observed a considerable disease control rate. Future strategies with this agent comprise right patient selection through the identification of reliable biomarkers and gene signatures predicting response and, considering good tolerability and convenience, combination strategies with novel agents and immune therapeutic agents.

Outcomes for patients with synchronous and metachronous primary lung cancer after diagnosis of head and neck cancer.

BACKGROUND: Not-infrequently patients with head and neck cancer are also diagnosed with synchronous lung cancer or metachronous primary lung cancer, which complicates the treatment decisions and prognosis. METHODS: Patients were identified from a database of patients with head and neck cancer with second primary non-small cell lung cancer (NSCLC). RESULTS: Thirty-four eligible patients (15 with synchronous lung cancer and 19 with metachronous lung cancer) were identified. Thirteen of 15 patients with synchronous lung cancer received curative intent treatment for head and neck cancer first. Six of 15 patients were in complete remission, 5 of 15 patients had died, and 4 were alive with progressive disease. Median time between 2 diagnoses was 47 months in the metachronous lung cancer group. Twelve patients had died, 3 were alive with disease, and 4 were lost to follow-up. Median survival from the time of lung cancer diagnosis was 13 months with a trend to better survival with synchronous lung cancer (15 vs 11 months; p = .11). CONCLUSION: Aggressive multidisciplinary management of second primary lung malignancies in patients with head and neck cancer can result in respectable long-term disease control particularly in patients with synchronous lung cancer. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1544-1549, 2017.

Efficacy of icotinib in lung squamous-cell cancer: A real-world experience from single institution.

AIM: Squamous cell carcinoma is a less common type of nonsmall cell lung cancer (NSCLC) which associates with a poor clinical prognosis and lacks specific therapy. This study aimed to evaluate the efficacy and safety of icotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has proven to be effective in EGFR-mutated NSCLC, in patients with lung squamous-cell cancer. METHODS: Retrospective analysis was conducted in patients who had advanced lung squamous-cell cancer confirmed by cytology or histology. Patients were treated orally with icotinib (125 mg, three times daily) until event of unacceptable toxicity, disease progression or death. The primary endpoint was overall survival. The secondary endpoints were progression-free survival, overall response rate and disease control rate. RESULTS: Between January 2014 and May 2016, 20 patients were enrolled and evaluated for the efficacy and safety of icotinib. Overall, the median overall survival and progression-free survival were 9.93 months (95% confidence interval (CI): 3.46-16.40) and 3.0 months (95% CI: 0.00-8.35), respectively. The overall response rate and disease control rate were 20% and 70%, respectively. For treatment-naive patients (n = 11), the overall survival and progression-free survival were 9.93 months (95% CI: 0.00-23.49) and 6.27 months (95% CI: 0.00-12.61); the response rate and disease control rate were 27.3% and 54.5%, respectively. The overall survival and progression-free survival of patients treated with second- or multiple-line icotinib treatment (n = 9) were 6.5 months (95% CI: 0.80-12.20) and 1.2 months (95% CI: 1.10-1.30). A total of 11 patients experienced at least one treatment-related adverse event, most of which were mild to moderate. The most common manifestations were rash (n = 6, 30%) followed by diarrhea (n = 2, 10%). CONCLUSION: Icotinib has demonstrated a favorable efficacy and safety profile in patients with advanced lung squamous-cell cancer.

Loss of PAR-3 protein expression is associated with invasion, lymph node metastasis, and poor survival in esophageal squamous cell carcinoma.

Disrupted cell polarity is a feature of epithelial cancers. The partitioning defective 3 (PAR-3) protein, a key component of the PAR complex that regulates the polarization of cells, is involved in tight junction formation at epithelial cell-cell contacts. Our previous study detected a homozygous deletion of the PAR-3 gene in esophageal squamous cell carcinoma (ESCC) cell lines and frequent copy number loss of the PAR-3 gene in primary ESCC. Here, we aimed to investigate the clinicopathological relevance of altered expression of the PAR-3 protein in primary ESCC. We immunohistochemically analyzed expression of the PAR-3 protein, as well as that of other tight junction proteins, ZO-1 and claudin-1, in 74 primary ESCCs. While the PAR-3 protein was expressed in the cytoplasm of basal cells, it was localized on the plasma membrane of suprabasal cells of normal squamous epithelium of the esophagus. Of the 74 ESCC tumors, 20 (27%), 11 (15%), and 13 (18%) were negative for PAR-3, ZO-1, and claudin-1 proteins, respectively. Negative PAR-3 protein expression, but not negative ZO-1 or claudin-1 expression, was significantly associated with deeper tumor invasion (P<.01), positive lymph node metastasis (P=.03), and advanced tumor stage (P=.01). Patients with PAR-3-negative tumors showed marginally significantly shorter overall survival after surgery than those with PAR-3-positive tumors (P=.053). In conclusion, these results suggest that PAR-3 protein expression is frequently lost in primary ESCC and that loss of the PAR-3 protein is associated with aggressive clinicopathological features of ESCC.

The prognostic impact of histological type on clinical outcomes of early-stage cervical cancer patients whom have been treated with radical surgery.

The aim of this study was to determine the prognostic impact of histological type among squamous cell carcinoma (SCC), adenocarcinoma (AC) and adenosquamous carcinoma (ASC) on the treatment outcome of early-stage cervical cancer patients after radical hysterectomy. The cohort comprised of 626 patients, diagnosed with stages IA2-IB1 cervical cancer between 1987 and 2013. Four hundred and one patients had SCC, 190 had AC and 35 had ASC. The 5-year disease-free survival (DFS) rates for AC, SCC and ASC were 89.3% (95%CI 83.2-93.2), 88.7% (95%CI 84.8-91.7) and 82.1% (95%CI 61.9-92.2), respectively (p = .594). In multivariate analyses, only older age and deep stromal invasion were statistically significantly associated with DFS, whereas histologic cell type was not (p = .524). Subgroup analysis showed that in the intermediate-high-risk groups, the SCC group had a significantly longer DFS, compared with the AC group or the ASC group (p = .001) while there was no DFS difference in the low-risk group. We believe that histologic cell type had no impact in low-risk early-stage cervical cancer patients. However, in the intermediate-high-risk groups, SCC is a more favourable factor for survival than AC/ASC.

Optimal pathological response indicated better long-term outcome among patients with stage IB2 to IIB cervical cancer submitted to neoadjuvant chemotherapy.

The role of pathological response in long-term outcome is still unclear in cervical cancer patients treated with neoadjuvant chemotherapy (NACT) in China. This study aimed to investigate the effect of optimal pathologic response (OPR) on survival in the patients treated with NACT and radical hysterectomy. First, 853 patients with stage IB2-IIB cervical cancer were included in a retrospective analysis; a Cox proportional hazards model was used to investigate the relationship between pathological response and disease-free survival (DFS). In the retrospective database, 64 (7.5%) patients were found to have achieved an OPR (residual disease <3 mm stromal invasion); in the multivariate Cox model, the risk of death was much greater in the non-OPR group than in the OPR group (HR, 2.61; 95%CI, 1.06 to 6.45; P = 0.037). Next, the role of OPR was also evaluated in a prospective cohort of 603 patients with cervical cancer. In the prospective cohort, 56 (9.3%) patients were found to have achieved an OPR; the log-rank tests showed that the risk of recurrence was higher in the non-OPR patients than in the OPR group (P = 0.05). After combined analysis, OPR in cervical cancer was found to be an independent prognostic factor for DFS.

The expression and prognostic value of protein tyrosine kinase 6 in early-stage cervical squamous cell cancer.

BACKGROUND: Protein tyrosine kinase 6 (PTK6) is overexpressed in many epithelial tumors and predicts poor prognosis. However, PTK6 expression status and its role in cervical squamous cell cancer are unknown. This study aimed to investigate the expression level and clinical significance of PTK6 in early-stage cervical squamous cell cancer. METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting analysis were performed to detect PTK6 mRNA and protein expression levels in 10 freshly frozen, early-stage cervical squamous cell cancer specimens and adjacent non-tumorous cervical tissues. The expression of PTK6 was detected using immunohistochemical staining in 150 formalin-fixed, paraffin-embedded, early-stage cervical squamous cell cancer sections and 10 normal cervical tissue sections. RESULTS: The mRNA and protein levels of PTK6 in cancer tissues were higher than those in adjacent non-tumorous cervical tissues. Immunohistochemical analysis showed that PTK6 was not expressed in normal cervical tissues but was overexpressed in the cytoplasm of cervical squamous cell cancer cells. The level of PTK6 expression was significantly associated with tumor grade (P = 0.020). The 5-year overall survival rate of patients with high PTK6 expression was lower than that of patients with low PTK6 expression (81.3% vs. 96.2%, P = 0.008). Multivariate Cox regression analysis showed that the expression level of PTK6 in cervical squamous cell cancer was an independent prognostic factor for patient survival (hazard ratio = 5.999, 95% confidence interval 1.622-22.191, P < 0.05). CONCLUSIONS: PTK6 is overexpressed in cervical squamous cell cancer. Increased PTK6 expression is associated with reduced 5-year overall survival. PTK6 expression is an independent prognostic predictor for cervical cancer.

Surgery Combined with Radiotherapy Improved Survival in Metastatic Esophageal Cancer in a Surveillance Epidemiology and End Results Population-based Study.

This retrospective study used a population-based national registry to determine the impact of local treatment modalities on survival in patients with metastatic esophageal cancer (EC). The Surveillance Epidemiology and End Results (SEER) database was used to identify patients with metastatic EC from 1988 to 2012. A total of 9,125 patients were identified. There were 426 patients underwent primary surgery, 4,786 patients were administered radiotherapy (RT) alone, 847 patients underwent surgery plus RT, and 3,066 patients without any local treatment. Multivariate analysis results indicated that year of diagnosis, age, race, histologic subtype, grade, and local treatment modalities were independent prognostic factors for overall survival (OS). The 5-year OS were 8.4%, 4.5%, 17.5%, and 3.4% in primary surgery, RT only, surgery plus RT, and no local treatment, respectively (P < 0.001). Subgroup analyses showed that the impact of RT was mainly reflected by preoperative radiotherapy, as patients received preoperative radiotherapy had significantly better OS than patients who underwent primary surgery alone and postoperative RT, the 5-year OS rates were 24.7%, 6.5%, and 7.8%, respectively, respectively (P < 0.001). Surgery plus RT, especially preoperative RT, may improve long-term survival of patients with metastatic EC.

Effect of postoperative radiotherapy for squamous cell cancer of the breast in a surveillance epidemiology and end results population-based study.

The therapeutic value of postoperative radiotherapy (RT) for squamous cell cancer of the breast (SCCB) is unclear. This retrospective study used a population-based national registry to determine the impact of postoperative RT on survival of women with SCCB. The Surveillance Epidemiology and End Results (SEER) database was used to identify females with SCCB who underwent primary surgical resection from 1973 to 2012. Kaplan-Meier survival analysis and Cox regression proportional hazard methods were used to determine the impact of RT following resection associated with cause-specific survival (CSS) and overall survival (OS). A total of 523 patients met the eligibility criteria. The median follow-up time was 55 months, the 10-year CSS and OS rates were 65.6%, and 46.0%, respectively. A total of 167 patients (31.9%) received postoperative RT. Multivariate analysis indicated that advanced pT and pN stage, and no postoperative RT were independently associated with poor OS; advanced pT and pN stage were independently associated with poor CSS. Postoperative RT was significantly associated with improved 10-year OS (54.5% vs. 42.0%, P =.001), but had no effect on CSS (P =.217). Analysis of patients with different stages of SCCB indicated that RT was associated with improved CSS (P =.047) and OS (P <.001) in those with stage II cancer and improved OS in patients with stage pN0 cancer (P <.001). Postoperative RT improved the survival of SCCB patients, especially in those with stage II and stage pN0 cancer.