Impact of Lymph Node Ratio on the Survival of Patients with Hypopharyngeal Squamous Cell Carcinoma: A Population-Based Analysis

Objective

To analyze the impact of the lymph node ratio (LNR, ratio of metastatic to examined nodes) on the prognosis of hypopharyngeal cancer patients.

Methods

SEER (Surveillance, Epidemiology and End Results)-registered hypopharyngeal cancer patients with lymph node metastasis were evaluated using multivariate Cox regression analysis to identify the prognostic role of the LNR. The categorical LNR was compared with the continuous LNR and pN classifications to predict cause-specific survival (CSS) and overall survival (OS) rates of hypopharyngeal cancer patients.

Results

Multivariate analysis of 916 pN+ hypopharyngeal cancer cases identified race, primary site, radiation sequence, T classification, N classification, M classification, the number of regional lymph nodes examined, the continuous LNR (Hazard ratio 2.415, 95% CI 1.707–3.416, P<0.001) and age as prognostic variables that were associated with CSS in hypopharyngeal cancer. The categorical LNR showed a higher C-index and lower Akaike information criterion (AIC) value than the continuous LNR. When patients (n = 1152) were classified into four risk groups according to LNR, R0 (LNR = 0), R1 (LNR ≤0.05), R2 (LNR 0.05–0.30) and R3 (LNR >0.30), the Cox regression model for CSS and OS using the R classification had a higher C-index value and lower AIC value than the model using the pN classification. Significant improvements in both CSS and OS were found for R2 and R3 patients with postoperative radiotherapy.

Conclusions

LNR is a significant prognostic factor for the survival of hypopharyngeal cancer patients. Using the cutoff points 0.05/0.30, the R classification was more accurate than the pN classification in predicting survival and can be used to select high risk patients for postoperative treatment.     

Prognostic Value of Metastatic Axillary Lymph Node Ratio for Chinese Breast Cancer Patients

Objective

The prevalence of breast cancer varies among countries and regions. This retrospective study investigated the prognostic value of the lymph node ratio (LNR) compared with the number of positive lymph nodes (pN) in Chinese breast cancer patients.

Methods

The medical records of female breast cancer patients (N = 2591) were retrospectively evaluated. The association of LNR and TMN staging system were compared with respect to overall, disease-free, and distant metastasis-free survival.

Results

Out of 2591 patients, 2495 underwent modified radical surgery and 96 received breast conserving surgery. All patients had adjuvant chemotherapy following surgery. The median follow up period 66.9 months (range 5–168 months). The 5-year and 10-year overall survival rates were 89.3% and 78.8%, respectively, and 5-year disease-free survival and distant metastasis-free survival rates were 81.6% and 83.5%, respectively. Univariate analysis indicated that in general T, pN, LNR, as well as tumor expression of the estrogen receptor, progesterone receptor, and HER2 were associated with overall, disease-free, and distant metastasis-free survival (all P-values <0.05). Mutlivariate analysis found pN stage and LNR were independent predictors of overall, disease-free, and distant metastasis-free survival (all P-values <0.001). If pN stage and LNR were both included in a multivariate analysis, LNR was still an independent prognostic factor for overall, disease-free, and distant metastasis-free survival (all P-values <0.001).

Conclusion

Our findings support the use of LNR as a predictor of survival in Chinese patients with breast cancer, and that LNR is superior to pN stage in determining disease prognosis.     

The Prognostic Value of Harvested Lymph Nodes and the Metastatic Lymph Node Ratio for Gastric Cancer Patients: Results of a Study of 1,101 Patients

Aim

To investigate whether the recommendation to remove 15 lymph nodes that is used in the staging system is necessary to assess gastric cancer progression and to evaluate whether our metastatic lymph node ratio dividing method, adapted from the AJCC’s (American Joint Committee on Cancer) 7^th TNM staging system, is helpful for the patients with fewer than 15 harvested lymph nodes.

Methods

We performed a retrospective study of 1101 patients with histologically diagnosed gastric cancer who underwent a D2 gastrectomy at the Sun Yat-sen University Cancer Center between January 2001 and December 2010. The Kappa and Chi-squared tests were employed to compare the clinicopathological variables. The Kaplan-Meier method and Cox regression were employed for the univariate and multivariate survival analyses.

Results

In the trial, 346, 601 and 154 patients had 0–14, 15–30 and more than 30 lymph nodes harvested, respectively. The median survival times of patients with different lymph nodes harvested in N0, N1, N2 and N3a groups were 45.43, 54.28 and 66.95 months (p = 0.068); 49.22, 44.25 and 56.72 months (p<0.001), 43.94, 47.97 and 35.19 months (p = 0.042); 32.88, 42.76 and 23.50 months (p = 0.016). Dividing the patients who had fewer than 15 lymph nodes harvested by the metastatic lymph node ratio at 0, 0.13 and 0.40, the median survival times of these 4 groups were 70.6, 50.5, 53.5 and 30.7 months (p<0.001). After re-categorising these 4 groups into the N0, N1, N2, N3a groups, the histological grade, T staging, premier N staging, and restaged N staging were the independent prognostic factors.

Conclusions

Large numbers of lymph nodes harvested in radical gastrectomy do not cause stage migration. For those patients with a small number of harvested lymph nodes, their stage should be divided by the metastatic lymph node ratio, referred to in the TNM staging system, to assign them an accurate stage.     

Non-Sentinel Lymph Node Metastasis Prediction in Breast Cancer with Metastatic Sentinel Lymph Node: Impact of Molecular Subtypes Classification

Introduction

To decipher the interaction between the molecular subtype classification and the probability of a non-sentinel node metastasis in breast cancer patients with a metastatic sentinel lymph-node, we applied two validated predictors (Tenon Score and MSKCC Nomogram) on two large independent datasets.

Materials and Methods

Our datasets consisted of 656 and 574 early-stage breast cancer patients with a metastatic sentinel lymph-node biopsy treated at first by surgery. We applied both predictors on the whole dataset and on each molecular immune-phenotype subgroups. The performances of the two predictors were analyzed in terms of discrimination and calibration. Probability of non-sentinel lymph node metastasis was detailed for each molecular subtype.

Results

Similar results were obtained with both predictors. We showed that the performance in terms of discrimination was as expected in ER Positive HER2 negative subgroup in both datasets (MSKCC AUC Dataset 1 = 0.73 [0.69–0.78], MSKCC AUC Dataset 2 = 0.71 (0.65–0.76), Tenon Score AUC Dataset 1 = 0.7 (0.65–0.75), Tenon Score AUC Dataset 2 = 0.72 (0.66–0.76)). Probability of non-sentinel node metastatic involvement was slightly under-estimated. Contradictory results were obtained in other subgroups (ER negative HER2 negative, HER2 positive subgroups) in both datasets probably due to a small sample size issue. We showed that merging the two datasets shifted the performance close to the ER positive HER2 negative subgroup.

Discussion

We showed that validated predictors like the Tenon Score or the MSKCC nomogram built on heterogeneous population of breast cancer performed equally on the different subgroups analyzed. Our present study re-enforce the idea that performing subgroup analysis of such predictors within less than 200 samples subgroup is at major risk of misleading conclusions.     

Mediastinal Lymph Node Dissection versus Mediastinal Lymph Node Sampling for Early Stage Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

Objective

This systematic review and meta-analysis aimed to evaluate the overall survival, local recurrence, distant metastasis, and complications of mediastinal lymph node dissection (MLND) versus mediastinal lymph node sampling (MLNS) in stage I–IIIA non-small cell lung cancer (NSCLC) patients.

Methods

A systematic search of published literature was conducted using the main databases (MEDLINE, PubMed, EMBASE, and Cochrane databases) to identify relevant randomized controlled trials that compared MLND vs. MLNS in NSCLC patients. Methodological quality of included randomized controlled trials was assessed according to the criteria from the Cochrane Handbook for Systematic Review of Interventions (Version 5.1.0). Meta-analysis was performed using The Cochrane Collaboration’s Review Manager 5.3. The results of the meta-analysis were expressed as hazard ratio (HR) or risk ratio (RR), with their corresponding 95% confidence interval (CI).

Results

We included results reported from six randomized controlled trials, with a total of 1,791 patients included in the primary meta-analysis. Compared to MLNS in NSCLC patients, there was no statistically significant difference in MLND on overall survival (HR = 0.77, 95% CI 0.55 to 1.08; P = 0.13). In addition, the results indicated that local recurrence rate (RR = 0.93, 95% CI 0.68 to 1.28; P = 0.67), distant metastasis rate (RR = 0.88, 95% CI 0.74 to 1.04; P = 0.15), and total complications rate (RR = 1.10, 95% CI 0.67 to 1.79; P = 0.72) were similar, no significant difference found between the two groups.

Conclusions

Results for overall survival, local recurrence rate, and distant metastasis rate were similar between MLND and MLNS in early stage NSCLC patients. There was no evidence that MLND increased complications compared with MLNS. Whether or not MLND is superior to MLNS for stage II–IIIA remains to be determined.     

Prognostic Value of the Lymph Node Ratio in Stage III Gastric Cancer Patients Undergoing Radical Resection

Objective

The aim of this study was to investigate the prognostic value of metastatic lymph node ratio (LNR) in patients having radical resection for stage III gastric cancer.

Methods

A total of 365 patients with stage III gastric cancer who underwent radical resection between 2002 and 2008 at Tianjin Medical University Cancer Institute and Hospital were analyzed. The cut-point survival analysis was adopted to determine the appropriate cutoffs for LNR. Kaplan–Meier survival curves and log-rank tests were used for the survival analysis.

Results

By cut-point survival analysis, the LNR staging system was generated using 0.25 and 0.50 as the cutoff values. Pearson''s correlation test revealed that the LNR was related with metastatic lymph nodes but not related with total harvested lymph nodes. Cox regression analysis showed that depth of invasion and LNR were the independent predictors of survival (p<0.05). There was a significant difference in survival between each pN stages classified by the LNR staging, however no significant difference was found in survival rate between each LNR stages classified by the pN staging.

Conclusions

The LNR is an independent prognostic factor for survival in stage III gastric cancer and is superior to the pN category in TNM staging. It may be considered as a prognostic variable in future staging system.     

Drug Allergy and the Risk of Lymph Node Metastasis in Rectal Cancer

Background

Previous epidemiologic studies have reported that a history of allergy is associated with reduced risk of colorectal cancer and other malignancies. However, no information is available for the association between allergy and the risk of lymph node metastasis. Our study was designed to determine this association in rectal cancer.

Methods

Patients who were treated at our hospital in the period from January 2003 to June 2011, and with a pathologically hospital discharge diagnosis of rectal adencarcinoma, were included. The clinical, laboratory, and pathologic parameters were analyzed. A multivariate logistic regression model was used to determine the association. Moreover, for type of allergic drug, sub-group analysis was performed.

Results

469 patients were included, including 231 with pathological lymph node metastasis (pLNM) (49.3%) and 238 without pLNM. Univariate analysis showed, compared with patients without pLNM, patients with pLNM had a younger age (60.6±12.8 yr vs. 63.6±12.2 yr, P = 0.012), a lower percentage of drug allergy (8.7% vs. 16.0%, P = 0.016), an increased CEA (median/interquartile-range 5.40/2.40–13.95 vs. 3.50/2.08–8.67, P = 0.009), and a lower serum sodium (141±3.1 mmol/L vs. 142±2.9 mmol/L, P = 0.028). Multivariate analysis showed that drug allergy was associated with a reduced risk of pLNM (OR = 0.553; 95% CI, 0.308–0.994; P = 0.048). In addition, our results showed that: (1) for tumor classification, patients with drug allergy had a higher percentage of group patients with pT1/pT2; and (2) for type of allergic drug, this inverse association was found for penicillins, not for other allergic drugs.

Conclusion

Drug allergy is associated with a reduced risk of pLNM in rectal cancer.     

Human Papillomavirus Prevalence in Invasive Laryngeal Cancer in the United States

Purpose

Human papillomavirus (HPV) is a major risk factor for specific cancers of the head and neck, particularly malignancies of the tonsil and base of the tongue. However, the role of HPV in the development of laryngeal cancer has not been definitively established. We conducted a population-based, cancer registry study to evaluate and characterize the genotype-specific prevalence of HPV in invasive laryngeal cancer cases diagnosed in the U.S.

Methods

The presence of genotype-specific HPV DNA was evaluated using the Linear Array HPV Genotyping Test and the INNO-LiPA HPV Genotyping Assay in formalin-fixed paraffin embedded tissue from 148 invasive laryngeal cancer cases diagnosed in 1993–2004 within the catchment area of three U.S. SEER cancer registries.

Results

HPV DNA was detected in 31 of 148 (21%) invasive laryngeal cancers. Thirteen different genotypes were detected. Overall, HPV 16 and HPV 33 were the most commonly detected types. HPV was detected in 33% (9/27) of women compared with 18% (22/121) of men (p = 0.08). After adjustment for age and year of diagnosis, female patients were more likely to have HPV-positive laryngeal tumors compared to males (adjusted OR 2.84, 95% CI 1.07–7.51). Viral genotype differences were also observed between the sexes. While HPV 16 and 18 constituted half of HPV-positive cases occurring in men, among women, only 1 was HPV 16 positive and none were positive for HPV 18. Overall 5-year survival did not vary by HPV status.

Conclusions

HPV may be involved in the development of a subset of laryngeal cancers and its role may be more predominant in women compared to men.     

Insulin-Like Growth Factor 1 Receptor (IGF1R) Expression and Survival in Operable Squamous-Cell Laryngeal Cancer

Introduction

Prognosis of patients with operable laryngeal cancer is highly variable and therefore potent prognostic biomarkers are warranted. The insulin-like growth factor receptor (IGFR) signaling pathway plays a critical role in laryngeal carcinogenesis and progression.

Patients and Methods

We identified all patients with localized TNM stage I–III laryngeal cancer managed with potentially curative surgery between 1985 and 2008. Immunohistochemical (IHC) expression of IGF1R-alpha, IGF1R-beta and IGF2R was evaluated using the immunoreactive score (IRS) and mRNA levels of important effectors of the IGFR pathway were assessed, including IGF1R, IGF-binding protein 3 (IGFBP3), suppressor of cytokine signaling 2 (SOCS2) and members of the MAP-kinase (MAP2K1, MAPK9) and phosphatidyl-inositol-3 kinase (PIK3CA, PIK3R1) families. Cox-regression models were applied to assess the predictive value of biomarkers on disease-free survival (DFS) and overall survival (OS).

Results

Among 289 eligible patients, 95.2% were current or ex smokers, 75.4% were alcohol abusers, 15.6% had node-positive disease and 32.2% had received post-operative irradiation. After a median follow-up of 74.5 months, median DFS was 94.5 months and median OS was 106.3 months. Using the median IRS as the pre-defined cut-off, patients whose tumors had increased IGF1R-alpha cytoplasm or membrane expression experienced marginally shorter DFS and significantly shorter OS compared to those whose tumors had low IGF1R-alpha expression (91.1 vs 106.2 months, p = 0.0538 and 100.3 vs 118.6 months, p = 0.0157, respectively). Increased mRNA levels of MAPK9 were associated with prolonged DFS (p = 0.0655) and OS (p = 0.0344). In multivariate analysis, IGF1R-alpha overexpression was associated with a 46.6% increase in the probability for relapse (p = 0.0374). Independent predictors for poor OS included node-positive disease (HR = 2.569, p<0.0001), subglottic/transglottic localization (HR = 1.756, p = 0.0438) and IGF1R-alpha protein overexpression (HR = 1.475, p = 0.0504).

Conclusion

IGF1R-alpha protein overexpression may serve as an independent predictor of relapse and survival in operable laryngeal cancer. Prospective evaluation of the IGF1R-alpha prognostic utility is warranted.     

Clinical Outcomes of Patients with Oral Cavity Squamous Cell Carcinoma and Retropharyngeal Lymph Node Metastasis Identified by FDG PET/CT

Purpose

Retropharyngeal lymph node (RPLN) metastasis is an uncommon finding in patients with oral cavity squamous carcinoma (OSCC). We sought to investigate the clinical outcomes, clinicopathological characteristics, and the priority of treatment with curative intent in OSCC patients with RPLN involvement.

Methods and Materials

Between January 2007 and January 2011, we identified 36 patients with primary RPLN metastases (n = 10) or RPLN relapse (n = 26). The follow-up continued until June 2013. Disease-specific survival (DSS), disease-free survival (DFS), and the potential benefits of salvage therapy served as the main outcome measures.

Results

The 2-year DSS and DFS rates of untreated patients with RPLN involvement were 20% and 24%, respectively. Level IV/V neck lymph node involvement was an adverse prognostic factor for DSS (P = 0.048) and DFS (P = 0.018). All of the patients presenting with neck lymph node involvement at level IV/V died within 6 months. Among patients who were treated for RPLN relapse, the 2-year DSS and DFS rates from the relapse day were 12.8% and 9.6%, respectively. Concomitant contralateral neck lymph node metastases (N2c) were associated with lower 2-year DSS (P = 0.005) and DFS (P = 0.011) rates. Moreover, five (55%) of the nine patients with recurrent disease in the contralateral RPLN had distant metastases within 6 months. Salvage therapy yielded the maximum survival benefit in patients without N2c disease and ipsilateral RPLN involvement alone (P = 0.005).

Conclusion

OSCC patients with RPLN involvement have poor outcomes. The risk factor for definitive treatment in OSCC patients with FDG PET/CT defined RPLN disease in primary disease was neck lymph node involvement at level IV/V and N2c and/or contralateral RPLN disease in recurrent disease. Treatment efforts with curative intent should be tailored according to individual risk factors.     

Association between Lymph Node Ratio and Disease Specific Survival in Breast Cancer Patients with One or Two Positive Lymph Nodes Stratified by Different Local Treatment Modalities

Purpose

Results of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial indicated that complete axillary node dissection (ALND) may not be warranted in some breast cancer patients with low tumor burden who are undergoing breast-conserving surgery following whole-breast irradiation. However, this study did not address patients undergoing mastectomy or those undergoing breast-conserving surgery without whole-breast radiotherapy. Given that lymph node ratio (LNR; ratio of positive lymph nodes to the total number removed) has been shown to be a prognostic factor in breast cancer, we first sought to determine the prognostic value of LNR in a low risk population comparable to that of the Z0011 trial and further to investigate whether the prognostic significance differs with local treatment modality.

Method

We used the Surveillance Epidemiology and End Results (SEER) database to identify breast cancer patients with T1-T2 tumor and 1–2 positive nodes. Patients were subclassified by the local therapy they underwent for the primary tumor. The prognostic value of LNR in predicting disease-specific survival (DSS) was examined in each treatment group.

Results

A total of 53,109 patients were included. In the subgroup of 20,602 patients who underwent lumpectomy following radiotherapy, LNR was not found to be significantly associated with DSS in both the univariate and multivariate model. For the 4,664 patients treated with mastectomy following radiotherapy, 6,811 treated with lumpectomy without radiotherapy and 21,031 with mastectomy without radiotherapy, LNR independently predict DSS in each of these subgroups.

Conclusions

Our results add evidence to the concept that axillary dissection could be omitted in patients with one or two positive nodes following breast-conserving surgery and whole breast radiation.     

Prognostic Value and Staging Classification of Retropharyngeal Lymph Node Metastasis in Nasopharyngeal Carcinoma Patients Treated with Intensity-modulated Radiotherapy

Background

The development of intensity-modulated radiotherapy (IMRT) has revolutionized the management of nasopharyngeal carcinoma (NPC). The purpose of this study was to evaluate the prognostic value and classification of TNM stage system for retropharyngeal lymph node (RLN) metastasis in NPC in the IMRT era.

Material and Methods

We retrospectively reviewed data from 749 patients with biopsy-proven, non-metastatic NPC. All patients received IMRT as the primary treatment. Chemotherapy was administered to 86.2% (424/492) of the patients with stage III or IV disease.

Results

The incidence of RLN metastasis was 64.2% (481/749). Significant differences were observed in the 5-year disease-free survival (DFS; 70.6% vs. 85.4%, P<0.001) and distant metastasis-free survival (DMFS; 79.2% vs. 90.1%, P<0.001) rates of patients with and without RLN metastasis. In multivariate analysis, RLN metastasis was an independent prognostic factor for disease failure and distant failure (P = 0.005 and P = 0.026, respectively), but not for locoregional recurrence. Necrotic RLN metastases have a negative effect on disease failure, distant failure and locoregional recurrence in NPC with RLN metastasis (P = 0.003, P = 0.018 and P = 0.005, respectively). Survival curves demonstrated a significant difference in DFS between patients with N0 disease and N1 disease with only RLN metastasis (P = 0.020), and marginally statistically significant differences in DMFS and DFS between N1 disease with only RLN metastasis and other N1 disease (P = 0.058 and P = 0.091, respectively). In N1 disease, no significant differences in DFS were observed between unilateral and bilateral RLN metastasis (P = 0.994).

Conclusions

In the IMRT era, RLN metastasis remains an independent prognostic factor for DFS and DMFS in NPC. It is still reasonable for RLN metastasis to be classified in the N1 disease, regardless of laterality. However, there is a need to investigate the feasibility of classifying RLN metastasis as N1a disease in future by a larger cohort study.     

Analysis of Lymph Node Metastasis Correlation with Prognosis in Patients with T2 Gastric Cancer

Purpose

To investigate the correlated factors for lymph node metastasis and prognosis for patients with T2 gastric cancer.

Methods

A total of 442 patients with T2 gastric cancer who underwent gastrectomy from January 1996 to December 2009 were evaluated. The clinicopathological parameters were analyzed for lymph node metastasis and prognosis, including gender, age, tumor size, tumor location, histological type, depth of invasion, vascular tumor emboli, nervous invasion, resection type, and pathological stage.

Results

The rate of lymph node metastasis was 45.9%. Univariate analysis showed that depth of invasion, tumor size, and vascular tumor emboli were associated with lymph node metastasis. Logistic regression demonstrated that depth of invasion, tumor size, and vascular tumor emboli were independently predictive factors for lymph node metastasis. The 5-year survival rate was 64.0%. Multivariate analysis showed that tumor size, tumor location, resection type, and pathological stage were independent prognostic factors. Based on tumor size, there were significant differences of 5-year survival between small size tumor (<6 cm) and large size tumor (≥6 cm) according to stage IIA (P = 0.006). Based on tumor location, there were significant differences of 5-year survival among different tumor location according to stage IB. Based on resection type, there were significant differences of overall 5-year survival between curative surgery and palliative surgery according to stage IIB (P = 0.015) and IIIA (P = 0.001).

Conclusion

Depth of invasion, tumor size, and vascular tumor emboli were independently predictive factors for lymph node metastasis. Tumor size, tumor location, resection type, and pathological stage were independent prognostic factors.     

Increased Expression of ATG10 in Colorectal Cancer Is Associated with Lymphovascular Invasion and Lymph Node Metastasis

Background

Autophagy has paradoxical and complex functions in cancer development, and autophagy-related genes (ATG) are key regulators in autophagy. Until now, more than 30 different ATG proteins have been identified in yeast, and their mammalian counterparts also have been reported. Although the roles of a few ATG proteins in cancer have been characterized, the role of ATG10 is almost completely unknown.

Methodology/Principal Findings

To investigate the clinicopathological role of ATG10 in colorectal cancer, we analyzed ATG10 expression in colorectal cancer tissues and cell lines. Protein expression analysis showed that ATG10 is highly increased in colorectal cancer (tissue - 18/37 cases, 48%; cell line –8/12 cell lines, 66%). Immunohistochemical analysis with clinicopathological features indicated a strong association of the up-regulation of ATG10 with tumor lymph node metastasis (p = 0.005) and invasion (p<0.001). Moreover, both 5-year disease free survival and overall survival rates of patients bearing tumors that did not express ATG10 were significantly higher than those of patients bearing ATG10-expressing tumors (p = 0.012).

Conclusion/Significance

Increased expression of ATG10 in colorectal cancer is associated with lymphovascular invasion and lymph node metastasis indicating that ATG10 may be a potential prognostic maker in colorectal cancer.     

Reduced Expression of ZDHHC2 Is Associated with Lymph Node Metastasis and Poor Prognosis in Gastric Adenocarcinoma

Background

Zinc finger, DHHC-type containing 2 (ZDHHC2), originally named as reduced expression associated with metastasis protein (REAM), has been proposed as a putative tumor/metastasis suppressor gene and is often aberrantly decreased in human cancers. However ZDHHC2 expression pattern and its clinical significance have not yet been investigated in gastric adenocarcinoma.

Methodology/Principal Findings

Quantitative Real-Time PCR (qRT-PCR) and immunostaining were performed to detect ZDHHC2 expression in gastric adenocarcinoma, and then the correlation between ZDHHC2 expression and clinicpathologic parameters, and patient survival was analyzed. Compared to the adjacent normal tissues, ZDHHC2 expression was significantly reduced in gastric tumor tissues as shown by qRT-PCR and immunostaining. Low expression of ZDHHC2 was observed in 44.7% (211/472) of gastric adenocarcinoma patients, and was associated significantly with lymph node metastasis (p<0.001) and histological grade (p<0.001). Multivariate Cox regression analysis indicated that ZDHHC2 expression had a significant, independent predictive value for survival of gastric cancer patients (HR = 0.627, p = 0.001).

Conclusions/Significance

Our data suggest that reduced ZDHHC2 expression is associated with lymph node metastasis and independently predicts an unfavorable prognosis in gastric adenocarcinoma patients.     

Mesenchymal Phenotype of CTC-Enriched Blood Fraction and Lymph Node Metastasis Formation Potential

Introduction

Circulating tumor cells (CTCs) that present mesenchymal phenotypes can escape standard methods of isolation, thus limiting possibilities for their characterization. Whereas mesenchymal CTCs are considered to be more malignant than epithelial CTCs, factors responsible for this aggressiveness have not been thoroughly defined. This study analyzed the molecular profile related to metastasis formation potential of CTC-enriched blood fractions obtained by marker unbiased isolation from breast cancer patients without (N−) and with lymph nodes metastases (N+).

Materials and Methods

Blood samples drawn from 117 patients with early-stage breast cancer were enriched for CTCs using density gradient centrifugation and negative selection with anti-CD45 covered magnetic particles. In the resulting CTC-enriched blood fractions, expression of CK19, MGB1, VIM, TWIST1, SNAIL, SLUG, HER2, CXCR4 and uPAR was analyzed with qPCR. Results were correlated with patients'' clinicopathological data.

Results

CTCs (defined as expression of either CK19, MGB1 or HER2) were detected in 41% (20/49) of N− and 69% (34/49) of N+ patients (P = 0.004). CTC-enriched blood fractions of N+ patients were more frequently VIM (P = 0.02), SNAIL (P = 0.059) and uPAR-positive (P = 0.03). Positive VIM, CXCR4 and uPAR status correlated with >3 lymph nodes involved (P = 0.003, P = 0.01 and P = 0.045, respectively). In the multivariate logistic regression MGB1 and VIM-positivity were independently related to lymph node involvement with corresponding overall risk of 3.2 and 4.2. Moreover, mesenchymal CTC-enriched blood fractions (CK19−/VIM+ and MGB1+ or HER2+) had 4.88 and 7.85-times elevated expression of CXCR4 and uPAR, respectively, compared with epithelial CTC-enriched blood fractions (CK19+/VIM− and MGB1+ or HER2+).

Conclusions

Tumors of N+ patients have superior CTC-seeding and metastatic potential compared with N- patients. These differences can be attributed to VIM, uPAR and CXCR4 expression, which endow tumor cells with particularly malignant phenotypes.     

The Incidence and Survival Rate of Population-Based Pancreatic Cancer Patients: Shanghai Cancer Registry 2004–2009

Background

Pancreatic cancer is a devastating disease with dismal prognosis. Large population-based evidence on its survival rate and influence factors is lacking in China.

Objective

This study aimed to depict the demographic factors, tumor characteristics, incidence rate and survival rate of pancreatic cancer cases in urban China.

Methods

The demographic factors, tumor characteristics were collected for all the pancreatic cancer cases identified during 2004 to 2009 from the Shanghai Cancer Registry. The survival time was ascertained through linkage of the Shanghai Cancer Registry and the Shanghai Vital Statistics Registry. The deadline of death certificates was the end of December 2012. Kaplan-Meier method and Cox proportional-hazards regression model were used to explore the survival rate and influence factors.

Results

11,672 new pancreatic cancer cases were identified among Shanghai residency during 2004 to 2009. The crude incidence rate of pancreatic cancer was increasing from 12.80/100,000 in 2004 to 15.66/100,000 in 2009, while the standardized incidence rate was about 6.70/100,000 and didn''t change a lot. The overall 5-year survival rate was 4.1% and the median survival time was 3.9 (95% Confidence Interval (CI) 3.8–4.0) months. Subjects had received surgical resection had improved survival (HR  = 0.742, 95% CI: 0.634–0.868) than its counterparts. In adjusted multivariable Cox proportional-hazard models, factors associated with poor survival included older age at diagnosis (age > = 70 years: hazard ratio (HR)  = 1.827, 95% CI: 1.614–2.067), male sex (HR  = 1.155, 95% CI: 1.041–1.281), distant disease at diagnosis (HR =  1.257, 95% CI: 1.061–1.488), positive lymph node (HR  = 1.236, 95% CI: 1.085–1.408), tumor stage (Stage IV HR  = 2.817, 95% CI: 2.029–3.909).

Conclusion

The age-adjusted incidence rate was stable and overall survival rate was low among pancreatic cancer patients of Shanghai residency. Early detection and improved treatment strategies are needed to improve prognosis for this deadly disease.     

Identification and Validation of a Multigene Predictor of Recurrence in Primary Laryngeal Cancer

Purpose

Local recurrence is the major manifestation of treatment failure in patients with operable laryngeal carcinoma. Established clinicopathological factors cannot sufficiently predict patients that are likely to recur after treatment. Additional tools are therefore required to accurately identify patients at high risk for recurrence. This study attempts to identify and independently validate gene expression models, prognostic of disease-free survival (DFS) in operable laryngeal cancer.

Materials and Methods

Using Affymetrix U133A Genechips, we profiled fresh-frozen tumor tissues from 66 patients with laryngeal cancer treated locally with surgery. We applied Cox regression proportional hazards modeling to identify multigene predictors of recurrence. Gene models were then validated in two independent cohorts of 54 and 187 patients (fresh-frozen and formalin-fixed tissue validation sets, respectively).

Results

We focused on genes univariately associated with DFS (p<0.01) in the training set. Among several models comprising different numbers of genes, a 30-probe set model demonstrated optimal performance in both the training (log-rank, p<0.001) and 1^st validation (p = 0.010) sets. Specifically, in the 1^st validation set, median DFS as predicted by the 30-probe set model, was 34 and 80 months for high- and low-risk patients, respectively. Hazard ratio (HR) for recurrence in the high-risk group was 3.87 (95% CI 1.28–11.73, Wald''s p = 0.017). Testing the expression of selected genes from the above model in the 2^nd validation set, with qPCR, revealed significant associations of single markers, such as ACE2, FLOT1 and PRKD1, with patient DFS. High PRKD1 remained an unfavorable prognostic marker upon multivariate analysis (HR = 2.00, 95% CI 1.28–3.14, p = 0.002) along with positive nodal status.

Conclusions

We have established and validated gene models that can successfully stratify patients with laryngeal cancer, based on their risk for recurrence. It seems worthy to prospectively validate PRKD1 expression as a laryngeal cancer prognostic marker, for routine clinical applications.     

Retrospective Analysis of Prognostic Factors in 205 Patients with Laryngeal Squamous Cell Carcinoma Who Underwent Surgical Treatment

Objectives

To investigate the most important factors affecting the prognosis of the patients with squamous cell carcinoma (SCC) of the larynx.

Methods

Based on the clinical and follow-up data, 205 patients with SCC of the larynx receiving total laryngectomy, partial laryngectomy, or CO₂ laser surgery in GuangDong General Hospital were retrospectively analyzed. A survival analysis was performed by the Kaplan-Meier method and a multivariable analysis of prognostic factors was carried out using the Cox proportional hazard model.

Results

Subtypes of carcinoma included 69.8% glottic and 30.2% supraglottic. Most patients were in N0 stage (77.6%), and 22.4% patients were in N1∼N3 stage. Over half of the patients were in T1∼T2 stage (55.1%), 20.0% in T3, and 24.9% in T4. Mean follow-up duration was 49.2 months. The survival rates 1, 2, and 3 years after the surgery were 99.0%, 91.7%, and 81.5%, respectively. The survival rate for those patients with clinical stage IV was significantly lower than for those with clinical stage I and II (p<0.001 and p = 0.013, respectively). The disease-free progression rates 1, 2, and 3 years after the surgery were 83.9%, 74.6%, and 71.2%, respectively. Futhermore, those patients with a Charlson score of 1 to 2 and ≥3 had higher risk of mortality than those with a Charlson score of 0 (hazard ratios of 1.8 and 2.41 p = 0.042 and p = 0.008). Multivariable analysis revealed that clinical stage, surgical margin, and comorbidity were significantly associated with both mortality and disease-free progression.

Conclusion

The surgical resection margin, clinical stage, and comorbidity were independent factors affecting the laryngeal cancer prognosis. The survival rates were lower for patients with advanced laryngeal cancer, positive surgical margins, or severe comorbidity, suggesting the importance of early diagnosis, early treatment, negative surgical margins, and conditions of comorbidity.     

Prognostic Value of CD166 Expression in Cancers of the Digestive System: A Systematic Review and Meta-Analysis

Objective

Many studies have reported the prognostic predictive value of CD166 as a cancer stem cell marker in cancers of the digestive system; however, its predictive value remains controversial. Here, we investigate the correlation between CD166 positivity in digestive system cancers and clinicopathological features using meta-analysis.

Methods

A comprehensive search in PubMed and ISI Web of Science through March of 2013 was performed. Only articles containing CD166 antigen immunohistochemical staining in cancers of the digestive system were included,including pancreatic cancer, esophageal cancer, gastric cancer and colorectal cancer. Data comparing 3- and 5-year overall survival along with other clinicopathological features were collected.

Results

Nine studies with 2553 patients who met the inclusion criteria were included for the analysis. The median rate of CD166 immunohistochemical staining expression was 56% (25.4%–76.3%). In colorectal cancer specifically, the results of a fixed-effects model indicated that CD166-positive expression was an independent marker associated with a smaller tumor burden (T category; RR = 0.93, 95%, CI: 0.88–0.98) but worse spread to nearby lymph nodes (N category; RR = 1.17, 95% CI: 1.05–1.30). The 5-year overall survival rate was showed relationship with cytoplasmic positive staining of CD166 (RR = 1.47 95% 1.21–1.79), but no significant association was found in the pool or any other stratified analysis with 3- or 5- year overall survival rate.

Conclusion

Based on the published studies, different cellular location of CD166 has distinct prognostic value and cytoplasmic positive expression is associated with worse prognosis outcome. Besides, our results also find CD166 expression indicate advanced T category and N-positive status in colorectal cancer specifically.