Advanced American Joint Committee On Cancer Stage Research Articles

Comparison of clinicopathological characteristics and survival outcomes between gallbladder mucinous adenocarcinoma and gallbladder adenocarcinoma: A propensity score-matched study.

Gallbladder mucinous adenocarcinoma (GBMAC) is a rare subtype of gallbladder adenocarcinoma (GBAC), with limited knowledge of its survival outcomes from small case series and single-center retrospective analysis. To compare the clinicopathological characteristics of GBMAC with typical GBAC and its prognostic factors to gain insights into this field. This study was conducted using data from the Surveillance, Epidemiology, and End Results database, including cases of GBMAC and typical GBAC diagnosed from 2010 to 2017. The Pearson chi-square test or Fisher exact test was used to examine the differences in clinicopathological features between these two cohorts. In addition, propensity score matching (PSM) analysis was performed to balance the selection biases. Univariate and multivariate Cox hazards regression analyses were performed to determine independent prognostic factors for cancer-specific survival (CSS) and overall survival (OS). The Kaplan-Meier curves and log-rank tests were used to assess the OS and CSS of GBMAC and typical GBAC patients. The clinicopathological and demographic characteristics of GBMAC were different from typical GBAC. They included a larger proportion of patients with unmarried status, advanced American Joint Committee on Cancer (AJCC) stage, higher T stage, higher N1 stage rate and lower N0 and N2 stage rates (P < 0.05). Multivariate analyses demonstrated that surgery [OS: Hazard ratio (HR) = 2.27, P = 0.0037; CSS: HR = 2.05, P = 0.0151], chemotherapy (OS: HR = 6.41, P < 0.001; CSS: HR = 5.24, P < 0.001) and advanced AJCC stage (OS: Stage IV: HR = 28.99, P = 0.0046; CSS: Stage III: HR = 12.31, P = 0.015; stage IV: HR = 32.69, P = 0.0015) were independent prognostic indicators for OS and CSS of GBMAC patients. Furthermore, after PSM analysis, there was no significant difference between GBMAC and matched typical GBAC patients regarding OS (P = 0.82) and CSS (P = 0.69). The biological behaviors of GBMAC are aggressive and significantly different from that of typical GBAC. However, they show similar survival prognoses. Surgery, chemotherapy, and lower AJCC stage were associated with better survival outcomes. Further research is needed in the future to verify these results.

Clinical Characteristics and Predictive Outcomes of Recurrent Nasopharyngeal Carcinoma-A Lingering Pitfall of the Long Latency.

Simple SummaryUnlike other head and neck cancers, nasopharyngeal carcinoma (NPC) with long-latent recurrence (>five years) is not rare. This study aims to investigate the clinical characteristics and outcomes of long-latent recurrent NPC. We found that 8.1% recurrence occurred after five years. About two thirds of these patients’ primary cancer belonged to the early stages, and almost half of the recurrence was a local recurrence. The five-year overall survival and disease-specific survival rate of long-latent recurrence was 19.7% and 24.5%, respectively. Most long-latent local recurrence was found in unresectable rT3 or rT4 cases, while one-third could not be detected by endoscopy due to recurrence in the skull base. A higher percentage of patients who died after long-latent recurrence were symptomatic with a follow-up interval more than six months, reflecting that delayed detection of recurrence may have a great impact on survival outcome. A long-term follow-up is necessary for early detection of NPC recurrence even after five years of disease-free interval.Purpose: To investigate the clinical characteristics, risk factors, and clinical outcomes of long-latent recurrence (>five years) of nasopharyngeal carcinoma (NPC). Methods: This retrospective study enrolled newly diagnosed NPC patients from the Chang Gung Research Database between January 2007 and December 2019. We analyzed the patients’ characteristics and survival outcomes after recurrence. Results: A total of 2599 NPC patients were enrolled. The overall recurrence rate was 20.5%, while 8.1% of patients had long-latent recurrence (>five years). These patients had a higher percentage of initial AJCC (The American Joint Committee on Cancer) stage I/II (60.5%, p = 0.001) and local recurrence (46.5%, p < 0.001). Unresectable rT3 and rT4 were found in 60% of patients when recurrence and 30% of local recurrence occurred in the skull base, which could not be detected by the regular endoscopy. The five-year overall survival rate of long-latent recurrence was 19.7%. Alive patients tended to be asymptomatic but have regular follow-ups with the interval less than six months. Multivariate analysis showed age and initial advanced AJCC stages were independent risk factors of death after recurrence. In contrast, patients with recurrence between two and five years, salvage surgeries, and regional recurrence had favorable survival outcomes. Conclusion: Long-latent NPC recurrence is not rare, and the survival outcome is poor. Regular follow-up for early detection of NPC recurrence is necessary even after five years of disease-free period.

Serum deprivation response functions as a tumor suppressor gene in papillary thyroid cancer.

The mechanism of papillary thyroid cancer (PTC) has shown numerous recurrently mutated genes, but the discovery of abnormal expression of novel tumor suppressor genes has been slow. The aim of our study is to explore the biological functions of SDPR in thyroid cancer. We reanalyzed the RNA-Seq data of PTC from The Cancer Genome Atlas (TCGA) database and found that serum deprivation response (SDPR) was significantly downregulated in PTC. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was performed to assess the expression of SDPR. Both loss- and gain-of-function experiments, and flow cytometry were performed to investigate the functions. SDPR was significantly downregulated in PTC. Reduced expression of SDPR was associated with larger tumor size, more serious lymph node metastasis, and advanced American Joint Committee on Cancer (AJCC) stage. Patients with lower SDPR expression had a shorter recurrence-free survival. SDPR expression and AJCC stage were independent predictors of poor recurrence-free survival (RFS). Moreover, cell proliferation, colony formation, and migration were inhibited after SDPR overexpression, whereas knockdown of SDPR exerted an oncogenic effect. SDPR induction also initiated the mesenchymal-epithelial transition, alongside suppressing AKT signaling and cyclin family expression. Apart from DNA methylation, LOC105373813, may also co-regulate SDPR expression by forming a stable hybrid with SDPR messenger RNA. Our study indicated that SDPR may function as a potential prognostic marker in PTC.

Management and outcomes among patients with sarcomatoid hepatocellular carcinoma: A population‐based analysis

Few data are available regarding the management and outcomes among patients with sarcomatoid hepatocellular carcinoma (HCC) due to its rarity. Patients diagnosed with sarcomatoid HCC from 2004 through 2015 were identified in the National Cancer Data Base. Overall survival (OS) was calculated among patients with sarcomatoid versus conventional HCC using a 1:3 propensity score matching based on sex, age, and American Joint Committee on Cancer (AJCC) stage of disease. The final analytic cohort included 104 patients with sarcomatoid HCC and 312 patients with conventional HCC. Patients with sarcomatoid HCC more often had a larger median tumor size (8.5cm vs 5.4cm; P<.001) and poorly or undifferentiated tumors (52.9% vs 13.8%; P<.001) compared with patients who hadconventional HCC. 5-year OS was worse among patients with sarcomatoid versus conventional HCC (5.7% vs 30.1%; P<.001). Subgroup analysis demonstrated worse 5-year OS among patients with sarcomatoid versus conventional HCC among patientstreated with eithercurative-intent or palliative therapies. Stage-specific subgroup analysis indicated a worse OS amongpatients with AJCC stage I, stage II, or stage III sarcomatoid HCC. On multivariable analysis, uninsured status, advanced AJCC stage (stage III/stage IV), and histological sarcomatoid subtype were independentlyassociated with worse outcomes (all P<.05). Sarcomatoid HCC is a very rare variant of HCC, which wasassociated with larger tumor size and worse tumor grade on presentation. On propensity score matched analyses that controlled for known confounding factors, patients with sarcomatoid HCC hada worse stage-for-stage long-term survival compared with patients who had conventional HCC.

FAM83D is associated with gender, AJCC stage, overall survival and disease-free survival in hepatocellular carcinoma.

Prognostic significance of family with sequence similarity 83, member D (FAM83D) in hepatocellular carcinoma (HCC) patients has not been well-investigated using Gene Expression Omnibus (GEO) series and TCGA database, we compared FAM83D expression levels between tumor and adjacent tissues, and correlated FAM83D in tumors with outcomes and clinico-pathological features in HCC patients. Validated in GSE33006, GSE45436, GSE84402 and TCGA, FAM83D was significantly overexpressed in tumor tissues than that in adjacent tissues (all P<0.01). FAM83D up-regulation was significantly associated with worse overall survival (OS) and disease-free survival (DFS) in HCC patients (Log rank P=0.00583 and P=4.178E-04, respectively). Cox analysis revealed that FAM83D high expression was significantly associated with OS in HCC patients [hazard ratio (HR) = 1.44, 95% confidence interval (CI) = 1.005–2.063, P=0.047]. Additionally, patients deceased or recurred/progressed had significantly higher FAM83D mRNA levels than those living or disease-free (P=0.0011 and P=0.0238, respectively). FAM83D high expression group had significantly more male patients and advanced American Joint Committee on Cancer (AJCC) stage cases (P=0.048 and P=0.047, respectively). FAM83D mRNA were significantly overexpressed in male (P=0.0193). Compared with patients with AJCC stage I, those with AJCC stage II and stage III–IV had significantly higher FAM83D mRNA levels (P = 0.0346 and P=0.0045, respectively). In conclusion, overexpressed in tumors, FAM83D is associated with gender, AJCC stage, tumor recurrence and survival in HCC.

Elevated Controlling Nutritional Status (CONUT) Score is Associated with Poor Long-term Survival in Patients with Low-grade Soft-tissue Sarcomas Treated with Surgical Resection.

Several studies have examined the Controlling Nutritional Status (CONUT) score, which is a screening tool for nutritional status and an effective biomarker for patient survival after cancer treatment. However, its role in soft-tissue sarcoma (STS) remains unknown. Because of the lack of predictive markers for survival in patients with STS, we aimed to determine the CONUT score's association with survival. (1) Is there a relationship between the CONUT score and clinicopathologic characteristics such as tumor size, tumor location, pathological grade, and advanced stage based on the American Joint Committee on Cancer (AJCC) guidelines? (2) Is the CONUT score associated with disease-free survival (DFS) and overall survival (OS) in patients treated surgically for STS, even when compared with other systemic inflammatory response markers? Between 1999 and 2016, 769 patients underwent R0 resection for STS at our institution. Adequate medical records and available followup data were required for inclusion in this study. Exclusion criteria were synchronous inflammatory diseases, unplanned excision, and neoadjuvant therapy. There were 658 patients (86%) who fulfilled all criteria. The minimum followup time was 24 months (median, 103 months; range, 61-147 months). The median age of the patients was 43 years (range, 5-85 years), and 265 patients (40%) were women. All patients had Stage I to IV tumors according to the 8 edition of the AJCC staging system. The grade classification was determined to be G1 in 130 patients (20%), G2 in 304 (46%), and G3 in 201 (31%). The CONUT score was calculated based on the serum albumin concentration, total peripheral lymphocyte count, and total cholesterol concentration. The score ranged from 0 to 12, with higher scores indicating worse nutritional status. The patients were classified into two groups according to a receiver operating characteristic curve analysis: the high (≥ 2) and low (0 or 1) CONUT score groups. There were 435 patients in the low CONUT score group and 223 in the high CONUT score group. We tested for an association between the CONUT scores and gender, age, tumor diameter, tumor depth, tumor grade, and AJCC stage using the chi-square and Fisher's exact methods. We also compared the strength of the association between postoperative survival and the CONUT scores, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) using multivariate Cox proportional hazard model analyses. High CONUT scores were associated with large tumor size (odds ratio [OR], 1.47; 95% CI, 1.06-2.04; p = 0.020), deep tumor location (OR, 1.66; 95% CI, 1.17-2.36; p = 0.004), high tumor grade (OR, 2.54; 95% CI, 1.56-4.14; p = 0.001), and advanced AJCC stage (OR, 1.86; 95% CI, 1.14-3.02; p < 0.001). The low CONUT score group exhibited a higher 5-year OS rate and longer OS than the high CONUT score group (82% versus 65%; odds ratio, 2.45; 95% CI, 1.27-4.72; p < 0.001; 81 versus 64 months, Z = -2.56; p < 0.001). A multivariate analysis indicated that an elevated CONUT score was an independent predictor of OS (hazard ratio [HR], 1.86; 95% CI, 1.47-4.14; p < 0.001) and DFS (HR, 1.63; 95% CI, 1.26-2.11; p < 0.001), but the NLR and PLR were not. In an individual subgroup analysis, the CONUT scores were associated with OS and DFS in the tumor diameter (< 5 or ≥ 5 cm) subgroup, tumor depth (superficial or deep) subgroup, tumor grade (G1 and G2) subgroup, and AJCC stage (I/II or III/IV) subgroup, but not in the G3 subgroup (p = 0.051 and p = 0.065). High CONUT scores were independently associated with aggressive tumor behavior and unfavorable survival for patients with low-grade, but not high-grade, resected STS. If these findings can be substantiated in larger studies, the CONUT score might be useful for predicting survival and help to develop new treatment strategies for nutrition interventions. Level III, therapeutic study.

Underlying liver disease and advanced stage liver cancer are associated with elevated neutrophil-lymphocyte ratio.

Background/AimsInflammation-based scores, such as the neutrophil-to-lymphocyte ratio (NLR), have been associated with prognosis in hepatocellular carcinoma (HCC); but variable cut-off values and potential lack of specificity have limited the utility of NLR. This study evaluates NLR in a large cohort of HCC patients.MethodsWe retrospectively reviewed 789 HCC cases (1993–2017) for demographics, tumor characteristics, treatment, and survival. NLR was stratified into NLR ≥1.5 and NLR ≥3 and analyzed for correlation with American Joint Committee on Cancer (AJCC) and Barcelona Clinic Liver Cancer (BCLC) stages. In 235 patients who underwent liver resection, survival and recurrence were evaluated by NLR.ResultsIn 789 HCC cases, mean NLR was increased with advanced AJCC and BCLC stages. Hepatitis C patients were less likely to have NLR ≥1.5 and ≥3. Non-alcoholic steatohepatitis patients were more likely to have NLR ≥3. Patients with tumor size >5 cm, rupture, or macrovascular invasion were more likely to have NLR ≥3. In patients treated with resection, NLR ≥3 predicted early recurrence (odds ratio [OR] 4.14, P<0.01) and overall recurrence (OR 4.05, P<0.01). Mean NLR was 4.30 in those with recurrence and 2.75 in those without recurrence. Patients with NLR ≥3 showed significantly worse survival compared to those with NLR <3 (P<0.01 by log-rank test).ConclusionsElevated NLR is associated with advanced cancer stage and aggressive tumor characteristics, such as large size, rupture, and invasion. NLR ≥3 was associated with early and overall recurrence after resection but varied with etiology. NLR may be a useful biomarker in predicting recurrence for HCC patients undergoing curative resection, but further studies are required to elucidate the effect of disease etiology.

Periostin overexpression is associated with worse prognosis in nasopharyngeal carcinoma from endemic area: a cohort study.

PurposeNasopharyngeal carcinoma (NPC) is a heterogeneous disease. We searched for genes that function in cell adhesion in GSE12452, a published transcriptomic database. We found that POSTN, which encodes periostin (POSTN), was significantly upregulated in NPC tumorigenesis. Herein, we sought to analyze the expression of POSTN and its prognostic significances in patients with NPC.Materials and methodsIn this single-institution retrospective study, we determined and analyzed POSTN expression by immunohistochemistry and H-score method, respectively, in 124 patients with NPC. The results indicated that POSTN expression was correlated with the clinicopathologic features, disease-specific survival (DSS), distant metastasis-free survival (DMFS), and local recurrence-free survival (LRFS) of NPC. We performed univariate and multivariate analyses to determinate the statistical significance.ResultsHigh POSTN expression was significantly associated with lymph node metastasis (p=0.004) and advanced American Joint Committee on Cancer (AJCC) stage (p=0.006). In univariate analysis, high POSTN expression served as a significant prognostic factor for worse DSS (p=0.0002), DMFS (p=0.0138), and LRFS (p=0.0028). In multivariate Cox regression analyses, which was adjusted for AJCC stages, POSTN expression was independently associated with cancer-related death (HR: 2.311; 95% CI: 1.327–4.027; p=0.003) and local tumor recurrence (HR: 3.187; 95% CI: 1.108–4.408; p=0.024).ConclusionHigh POSTN expression is associated with tumor aggressiveness and worse clinical outcomes in NPC, indicating that it may be a potential prognostic biomarker and a therapeutic target.

P16INK4a overexpression as a predictor of survival in ocular surface squamous neoplasia

AimsTo evaluate the expression and methylation status of the p16INK4a gene in early and advanced American Joint Committee on Cancer (AJCC) stages of ocular surface squamous neoplasia (OSSN) and to...

A study of BRAF mutation in colorectal carcinoma in Indian population.

BRAF mutation has been extensively studied and associated with various tumors. Targeted therapeutic intervention against BRAF mutation is established modality against many such tumors. Various studies have estimated that the prevalence of BRAF mutation in colorectal carcinoma (CRC) is 5%-25%. Considering epidemiology differences from Western population and paucity of studies on BRAF mutation in CRC in Asian patients, the present study was done to study the BRAF mutation in CRC in Indian population. The aim is to study the distribution of BRAF mutation and its correlation with the American Joint Committee on Cancer (AJCC) stage, grade, and other clinicopathological parameters in CRC. This was a cross-sectional study. Immunohistochemistry study was done using BRAFV600E monoclonal antibody (Clone VE1) for 65 consecutive cases of CRC in a tertiary care center. The results were statistically analyzed using SPSS version 2.0. This study found that BRAF mutation is not significantly present in CRC as only 4.6% of cases were positive for BRAFV600E mutation. However, there was statistically significant relation between increasing AJCC stage and BRAF mutation. This study concluded that BRAF mutation is not prevalent in Indian population with CRC. However, it is significantly related with advanced AJCC stages.

Identifying pretreatment baseline factors predictive of distant metastasis in patients with nasopharyngeal carcinoma after radiotherapy.

This retrospective study was performed to identify pretreatment baseline factors that could predict the development of distant metastasis (DM) in patients with nasopharyngeal carcinoma (NPC).A cohort of 119 NPC patients undergoing radiotherapy (RT) or chemoradiotherapy (CRT) were recruited into the study. Among them, 51 developed DM (DM group) within 3 years after treatment and 68 did not (DM-free group). Various clinicopathological factors were measured before the treatment and analyzed by univariate as well as multivariate analyses for the potential correlation with DM development.Univariate analysis revealed that increased peripheral lactate dehydrogenase (LDH) level, lower lymphocyte–monocyte ratio (LMR), higher neutrophil–lymphocyte ratio (NLR), advanced American Joint Committee on Cancer (AJCC) stage, advanced T stage, and advanced N stage were significantly correlated with the presence of DM. Multivariate analysis identified advanced AJCC stage and high LDH level were independent predictive factors for DM.Routinely measured pretreatment clinical factors, including AJCC state and serum LDH level, could independently predict DM. These factors will benefit the selection of appropriate treatment options and improve the overall survival of NPC patients.

Clinicopathological Significance of Large Tumor Suppressor (LATS) Expression in Gastric Cancer.

PurposeThe aims of this study were to evaluate the expression of the large tumor suppressor (LATS) genes LATS1 and LATS2 by immunohistochemical staining of gastric cancer, and to evaluate the clinicopathological significance of LATS expression and its correlation with overall survival (OS).Materials and MethodsLATS1 and LATS2 expression in a tissue microarray was detected by immunohistochemistry, using 264 gastric cancer specimens surgically resected between July 2006 and December 2009.ResultsLow expression of LATS1 was significantly associated with more advanced American Joint Committee on Cancer (AJCC) stage (P=0.001) and T stage (P=0.032), lymph node (LN) metastasis (P=0.040), perineural invasion (P=0.042), poor histologic grade (P=0.007), and diffuse-type histology by the Lauren classification (P=0.033). Low expression of LATS2 was significantly correlated with older age (≥65, P=0.027), more advanced AJCC stage (P=0.001) and T stage (P=0.001), LN metastasis (P=0.004), perineural invasion (P=0.004), poor histologic grade (P<0.001), and diffuse-type histology by the Lauren classification (P<0.001). Kaplan-Meier survival analysis revealed significantly poor OS rates in the groups with low LATS1 (P=0.037) and LATS2 (P=0.037) expression.ConclusionsExpression of LATS1 or LATS2 is a significant marker for a good prognosis in patients with gastric cancer.

Black Patients with Colorectal Cancer Have More Advanced Cancer Stage at Time of Diagnosis: A Community-Based Safety-Net Hospital Experience.

Colorectal cancer (CRC) remains a leading cause of morbidity and mortality in the U.S. Disparities in access to care contribute to advanced CRC stage at diagnosis, and these disparities are most pronounced among underserved populations and ethnic minorities. We aim to evaluate race/ethnicity-specific disparities in CRC stage at diagnosis among an ethnically diverse, urban safety-net hospital. We retrospectively evaluated all adult CRC patients diagnosed from January 1, 2009 to October 1, 2015. CRC cases were confirmed by histopathology specimens from biopsies and/or surgical resection. CRC staging utilized American Joint Committee on Cancer (AJCC) staging systems and were stratified by race/ethnicity. Multivariate logistic regression models were utilized to evaluate disparities in AJCC stage at presentation (stage 3-4 vs. stage 0-2). Among 311 patients with CRC [51.5% male, 25.3% black, 18.7% Hispanic, 32.0% Asian, and mean age at diagnosis 58.1years (SD 10.3)] 61.4% had advanced ACC stage 3-4 CRC at diagnosis. Among black patients with CRC, 73.3% had AJCC stage 3-4 cancer at time of diagnosis. On multivariate regression, blacks were nearly four times more likely to have advanced AJCC stage 3-4 CRC at diagnosis compared to whites (OR 3.70; 95% CI 0.97-14.11; p = 0.055). Among a diverse underserved population, over 60% of CRC were AJCC stage 3-4 at diagnosis, and nearly 75% of blacks with CRC had AJCC stage 3-4 at diagnosis. Advanced stage CRC at diagnosis limits options for potentially curative therapies, and increases the risk for cancer recurrence and mortality.

Glutamate Decarboxylase 1 Overexpression as a Poor Prognostic Factor in Patients with Nasopharyngeal Carcinoma

Background: Glutamate decarboxylase 1 (GAD1) which serves as a rate-limiting enzyme involving in the production of γ-aminobutyric acid (GABA), exists in the GABAergic neurons in the central nervous system (CNS). Little is known about the relevance of GAD1 to nasopharyngeal carcinoma (NPC). Through data mining on a data set derived from a published transcriptome database, this study first identified GAD1 as a differentially upregulated gene in NPC. We aimed to evaluate GAD1 expression and its prognostic effect on patients with early and locoregionally advanced NPC.Methods: We evaluated GAD1 immunohistochemistry and performed an H-score analysis on biopsy specimens from 124 patients with nonmetastasized NPC receiving treatment. GAD1 overexpression was defined as an H score higher than the median value. The findings of such an analysis are correlated with clinicopathological behaviors and survival rates, namely disease-specific survival (DSS), distant-metastasis-free survival (DMeFS), and local recurrence-free survival (LRFS) rates.Results: GAD1 overexpression was significantly associated with an increase in the primary tumor status (p < 0.001) and American Joint Committee on Cancer (AJCC) stages III-IV (p = 0.002) and was a univariate predictor of adverse outcomes of DSS (p = 0.002), DMeFS (p < 0.0001), and LRFS (p = 0.001). In the multivariate comparison, in addition to advanced AJCC stages III-IV, GAD1 overexpression remained an independent prognosticator of short DSS (p = 0.004, hazard ratio = 2.234), DMeFS (p < 0.001, hazard ratio = 4.218), and LRFS (p = 0.013, hazard ratio = 2.441) rates.Conclusions: Our data reveal that GAD1 overexpression was correlated with advanced disease status and may thus be a critical prognostic indicator of poor outcomes in NPC and a potential therapeutic target to facilitate the development of effective treatment modalities.

Prediction of survival and cancer recurrence using metabolic volumetric parameters measured by 18F-FDG PET/CT in patients with surgically resected rectal cancer.

The goal of the present study was to determine whether the volumetric parameters such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG) measured by F-FDG PET/CT could be used as prognostic factors for the recurrence-free survival (RFS) and overall survival (OS) in patients with surgically resected rectal cancer. A retrospective review identified 73 patients with surgically resected rectal cancer who received F-FDG PET/CT. Survival analysis was conducted using Kaplan-Meier analysis, and survival curves stratified by age, sex, lymph node status, surgical resection margin, American Joint Committee on Cancer (AJCC) stage, and volumetric parameters of F-FDG PET/CT were generated for the estimation of OS and RFS. Independent predictive factors for survival were determined using Cox proportional hazards model. High MTV, high TLG, advanced AJCC stage, lymph node (+), and surgical margin (+) group showed shorter OS in rectal cancer patients. Cox proportional hazards regression analysis showed that only surgical margin (+) was associated with poor OS. The early AJCC stage, lower MTV, and lower TLG were associated with better RFS in the current study. Cox proportional hazards regression analysis reveals that the surgical margin (+) was the potent predictor of OS. However, none of the factors was associated with RFS. In conclusion, the results of this study suggest that volumetric parameters of F-FDG PET/CT could be significant prognostic factors in surgically resected rectal cancer.

The Expression of PTEN Is Associated With Improved Prognosis in Patients With Ampullary Adenocarcinoma After Pancreaticoduodenectomy

Phosphatase and tensin homolog (PTEN) is one of the most frequently inactivated tumor suppressor genes in sporadic cancers. Somatic mutations of PTEN occur in many tumors including those of the gastrointestinal and hepatobiliary tracts. Loss of PTEN expression is associated with poor prognosis in patients with metastatic colonic adenocarcinoma, gastroesophageal junction adenocarcinoma, gastric adenocarcinoma, and pancreatic ductal adenocarcinoma. To study the expression of PTEN and its significance in ampullary adenocarcinoma (AA). We constructed tissue microarrays by using archival tissue from 92 patients (55 males, 37 females; median age, 63 years; age range, 37 to 87 years) with previously untreated AA who underwent pancreaticoduodenectomy at our institution. PTEN expression was evaluated by immunohistochemistry, scored semiquantitatively (based on staining intensity and percentage positive tumor cells), and correlated with clinicopathologic features and survival. Of 92 cases, 23 (25.0%) were PTEN negative. Loss of PTEN expression correlated with lymph node metastasis (P = .004), advanced American Joint Committee on Cancer (AJCC) stage (P = .02), and higher frequency of recurrence (P = .03). Patients with PTEN-negative tumors had shorter disease-free survival (DFS, mean: 89.0 ± 20.8 months) and overall survival (OS, mean: 93.1 ± 19.1 months) than those with PTEN-positive tumors (DFS, mean: 161.4 ± 11.7 months, P = .01; OS, mean: 175.4 ± 11.0 months, P = .001). In multivariate analyses, PTEN expression was a prognostic factor for both DFS and OS, independent of AJCC stage, lymph node status, pathologic tumor (pT) stage, and differentiation. Loss of PTEN expression is associated with poor DFS and OS in patients with AA after curative surgery. PTEN expression may be used as a prognostic marker for patients with resected AA.

Fibronectin overexpression is associated with latent membrane protein 1 expression and has independent prognostic value for nasopharyngeal carcinoma

Despite recent improvements in the diagnosis and treatment, the final outcomes in patients with nasopharyngeal carcinomas (NPC) still remain suboptimal. Through data mining from published transcriptomic database with further bioinformatic validation, fibronectin (FN1) was identified as a differentially upregulated gene in NPC tissues, which implicates the transition from epithelial to mesenchymal phenotype (EMT) and promotes metastasis. Given the roles of fibronectin in risk stratification and in the frontline therapeutics of common carcinomas, such as renal cell cancer, we explored fibronectin immunoexpression status and its associations with clinicopathological variables and survival in a well-defined cohort of NPC patients. Fibronectin immunohistochemistry was retrospectively performed and analyzed using H-score for 124 biopsy specimens from NPC patients who received standard treatment without distant metastasis at initial diagnosis. Those cases with H-score higher than the median value were regarded as fibronectin overexpression. The findings were correlated with clinicopathological variables, EBV latent membrane protein 1 (LMP1) expression, disease-specific survival (DSS), distant metastasis-free survival (DMFS), and local recurrence-free survival (LRFS). Fibronectin overexpression was significantly associated with American Joint Committee on Cancer (AJCC) stages III-IV (p = 0.019) and LMP1 expression (p = 0.004), and univariately predictive of adverse outcomes for DSS, DMFS, and LRFS (all p < 0.0001). In the multivariate comparison, fibronectin overexpression still remained prognostically independent to portend worse DSS (p < 0.01, hazard ratio = 5.958), DMFS (p < 0.01, hazard ratio = 5.728), and LRFS (p < 0.01, hazard ratio = 5.411) together with a vanced AJCC stages III-IV. Fibronectin is upregulated in a subset of NPCs, and its increased immunoexpression significantly correlated with advanced features, justifying the potentiality of fibronectin as a theragnostic biomaker of NPC.

Association of Positive Transection Margins with Gastric Cancer Survival and Local Recurrence

To examine the association between positive resection margins and survival and local recurrence in patients with gastric cancer undergoing resection with curative intent. Patients who underwent curative intent resection for gastric carcinoma from 1985 to 2010 were identified from a prospectively maintained database. Positive margins were defined as disease present at the line of luminal transection. Clinicopathological features and outcome of patients undergoing gastrectomy with negative and positive margins were compared. Among 2384 patients undergoing curative intent resection, 108 (4.5%) had positive margins. Positive margins were associated with higher American Joint Committee on Cancer (AJCC) stage, T stage, N stage, median number of positive nodes, diffuse Lauren type, and poorly differentiated tumors. Treatment of positive margins consisted of: observation (39%), chemoradiotherapy (26%), chemotherapy (20%), repeat resection (10%), radiotherapy (4%), and unknown (1%). Multivariate analysis of the entire cohort demonstrated margin status, T stage, N stage, grade, and perineural invasion to be independent predictors of survival. Margin status was an independent predictor of survival in patients with ≤3 positive nodes or T1-2 disease but was not in patients with >3 positive nodes or T3-4 disease. Local recurrence occurred in 16% of patients with a positive margin. We identified no factors predictive of local recurrence in patients with positive margins. Positive resection margin is associated with advanced AJCC stage and aggressive tumor biology but remains an independent predictor of worse survival. The significance of a positive margin in gastric cancer is confined to patients with nontransmural disease and/or limited nodal involvement.

The correlation of cortactin and fascin‐1 expression with clinicopathological parameters in pancreatic and ampulla of Vater adenocarcinoma

Cortactin and fascin-1 are important factors affecting progression and metastasis of carcinomas. We tested the hypothesis that cortactin and fascin expression has significant correlation with clinicopathological parameters in pancreatic and ampulla of Vater adenocarcinomas. Immunohistochemical analysis of cortactin and fascin-1 was performed in 50 pancreatic and 40 ampulla of Vater adenocarcinomas. The specimens were from 29 R0, 8 R1, and 13 palliative resections of pancreatic adenocarcinomas and 18 R0, 14 R1, and 8 palliative resections of ampulla of Vater adenocarcinomas. 'R0' resection is defined by complete removal of the tumor and histologically negative surgical margins and 'R1' resection indicates the presence of microscopically residual disease at the surgical margins. The level of expression was assessed by scoring the intensity of cytoplasmic or membranous immunostaining on a 4-point scale. Higher immunostaining scores of cortactin and fascin-1 were both significantly correlated with histological grade, American Joint Committee on Cancer (AJCC) stage, and survival rate in all patients. In conclusion, overexpression of cortactin and fascin-1 implies poorer tumor differentiation, advanced AJCC stage, and shorter survival rate in pancreatic and ampulla of Vater adenocarcinomas.

Clinical Correlates of NRAS and BRAF Mutations in Primary Human Melanoma

NRAS and BRAF mutations are common in cutaneous melanomas, although rarely detected mutually in the same tumor. Distinct clinical correlates of these mutations have not been described, despite in vitro data suggesting enhanced oncogenic effects. This study was designed to test the hypothesis that primary human cutaneous melanomas harboring mutations in NRAS or BRAF display a more aggressive clinical phenotype than tumors wild type at both loci. Microdissection of 223 primary melanomas was carried out, followed by determination of the NRAS and BRAF mutational status. Genotypic findings were correlated with features known to influence tumor behavior including age, gender, Breslow depth, Clark level, mitotic rate, the presence of ulceration, and American Joint Committee on Cancer (AJCC) staging. Breslow depth and Clark level varied significantly among the genotypes, with NRAS mutants showing the deepest levels and wild-type tumors the least depth. Ulceration also differed significantly among the genotypes, with BRAF mutants demonstrating the highest rate. In addition, tumors with mutated NRAS were more likely to be located on the extremities. Patients whose tumors carried either mutation presented with more advanced AJCC stages compared with patients with wild-type tumors, and specifically, were more likely to have stage III disease at diagnosis. Overall survival did not differ among the 3 groups. Distinct clinical phenotypes exist for melanomas bearing NRAS and BRAF mutations, whether considered together or separately, and are associated with features known to predict aggressive tumor behavior. The impact of these mutations is most evident at earlier stages of disease progression.