Number Of Tumor-positive Lymph Nodes Research Articles

Prognostic value of PSMA, c-MET and E-cadherin in salivary duct carcinoma.

Salivary duct carcinoma (SDC) is a rare and aggressive subtype of salivary gland cancer. Androgen receptor (AR) (96%) and HER2 (29-46%) expression, and a high propensity for regional lymph node metastases are hallmarks of the disease. We hypothesized that c-MET, E-cadherin, PSMA tumor and PSMA neovascular expression may be prognostic factors in SDC. Expression levels of these proteins were established on tissue microarrays containing 165 primary SDC tumor specimens. Association with survival was studied with Kaplan-Meier curves, and univariable and multivariable Cox regression models. Furthermore, association with lymph node status, AR and HER2 expression, and gender was studied. We found that patients with high PSMA tumor expression showed a significantly longer overall survival (OS) (median 83 vs. 43 months, P = 0.022), a trend towards a longer DFS (median 51 vs. 22 months, P = 0.094), and significantly reduced hazard ratio for death in the univariable Cox regression model (HR 0.46, P = 0.034). In the multivariable model only a high number of tumor-positive lymph nodes and high age (>80) at diagnosis were prognostic for poor OS. High PSMA tumor expression was also significantly associated with low N-stage (P = 0.001) and expression was higher in women versus men (P = 0.029). High PSMA tumor expression and E-cadherin loss were significantly associated with strong and weak AR-expression, respectively (P = 0.033 and P = 0.007). None of the factors were significantly associated with HER2 expression. c-MET, E-cadherin, and tumor and neovascular PSMA expression are no independent prognostic factors in SDC.

The Negative Impact of Body Mass Index on the Tumor Microenvironment in Colon Cancer: Results of a Prospective Trial

The association between tumor mismatch repair status and obesity in colon cancer is not well understood. The authors of this study hypothesized that mismatch repair deficiency in colon cancer may be associated with a lower Body Mass Index (BMI) and improved patient outcome due to an enhanced tumor immune microenvironment. For this study, 70 patients were randomly selected from a prospective trial evaluating nodal ultrastaging for colon cancer. The mismatch repair status of tumors and immunomarker expression were correlated with clinicopathologic characteristics and evaluated for disease-free survival. Patients with mismatch repair-deficient tumors (n=11) had a lower mean BMI than those with mismatch repair-proficient tumors (n=59) (22.16 vs. 26.30 kg/m2, respectively; p=0.029).The findings showed that CD3+ T cells were inversely associated with mismatch repair proficiency (p=0.048). Mismatch repair-proficient tumors in nonobese patients (BMI <30kg/m2) versus obese patients had a higher density of CD8+ (p=0.008) and FOXP3+ (p=0.005) T cells. Multivariable analysis linked CD4+ (hazard ratio [HR] 0.52; 95% confidence interval [CI] 0.35-0.76), CD8+ (HR 0.67; 95% CI 0.50-0.89), and number of tumor-positive lymph nodes (HR 1.19; 95% CI 1.03-1.36) to disease-free survival for patients with mismatch repair-proficient tumors. Tumor mismatch repair status and obesity are correlated in patients with colon cancer. Increased intratumoral T cells in nonobese patients suggests an unexplored link between tumor mismatch repair and immunoprofile.

Prognostic Utility of Immunoprofiling in Colon Cancer: Results from a Prospective, Multicenter Nodal Ultrastaging Trial

Retrospective data indicate that immunoprofiling of T cell markers can be prognostic in colon cancer. Prospective T cell immunoprofiling of colon cancer has not been well defined for patients whose lymph nodes are ultrastaged. A prospective cohort was selected from patients enrolled in an ongoing phase II multicenter trial of nodal ultrastaging for colon cancer. Primary tumor specimens from 89 patients were analyzed by immunohistochemistry for the T cells CD3(+), CD4(+), CD8(+), and FOXP3(+). Lymphocyte populations were quantified with digital image analysis. Results were examined for their association with 5-year disease-free survival along with TNM stage and clinicopathologic variables. Longer disease-free survival was associated with higher CD3(+) counts at the invasive margin (IM) (p= 0.005), higher CD8(+) counts at the tumor center (TC) and IM (p= 0.002), a lower CD4(+)/CD8(+) ratio at the TC+IM (p= 0.027), and a higher CD8(+)/FOXP3(+) ratio at the TC+IM (p= 0.020). After multivariable analysis, CD8(+) at the TC+IM (p= 0.002), the CD8(+)/FOXP3(+) ratio at the TC+IM (p= 0.004), and the number of tumor-positive lymph nodes (p= 0.003) remained significant. This is the first prospective demonstration of the prognostic utility of immunoprofiling in colon cancer after nodal ultrastaging. Staging based on tumor immunoprofile can augment TNM staging and provide targets for specific immunotherapies.

Relationships between TIMP-1, CAIX, and clinical outcomes in Egyptian breast cancer

Serum levels of carbonic anhydrase IX (CAIX) and the tissue inhibitor of metalloproteinase 1 (TIMP-1) have been demonstrated to be associated with clinical outcomes. Elevated TIMP-1 levels have been associated with a poor prognosis of breast cancer. Therefore, this study was performed to explore the relationships between serum CAIX, TIMP-1, and clinical outcomes. One hundred and five female breast cancer patients, who do not receive adjuvant therapy at Mansoura University Hospital were recruited with informed consent for this study. Preoperative serum levels of CAIX and TIMP-1 were measured using an enzyme-linked immunosorbent assay. Among the breast cancer patients, 16.1 and 20.9 % had elevated TIMP-1 and CAIX l levels, respectively. In addition, 13.3 % had elevated both CAIX and TIMP-1 levels. Elevated serum levels CAIX was significantly associated with advanced histological grade, estrogen receptor status and progesterone receptor status. Moreover, Elevated TIMP-1 was significantly associated with number of tumor-positive lymph nodes and advanced histological grade. In Kaplan–Meier analysis, the disease-free survival (DFS) was lower in patients with high serum levels of CAIX and TIMP-1 compared to patients with normal serum concentration of CAIX and TIMP-1. Including TIMP-1, CAIX, and established prognostic factors in the multivariate analysis, the presence of elevated CAIX and TIMP-1 levels remained independent predictors of overall survival time (OS). A high serum TIMP-1 and CAIX levels were significantly associated with poorer DFS and OS among Egyptian primary breast cancer patients with elevated serum levels of CAIX and TIMP-1.

Reduced Lymph Node Yield in Rectal Carcinoma Specimen After Neoadjuvant Radiochemotherapy Has No Prognostic Relevance

In colorectal surgery UICC/AJCC criteria require a yield of 12 or more locoregional lymph nodes for adequate staging. Neoadjuvant radiochemotherapy for rectal carcinoma reduces the number of lymph nodes in the resection specimen; the prognostic impact of this reduced lymph node yield has not been determined. One hundred two patients with uT3 rectal carcinoma who were receiving neoadjuvant radiochemotherapy were compared with 114 patients with uT3 rectal carcinoma who were receiving primary surgery followed by adjuvant radiochemotherapy. Total lymph node yield and number of tumor-positive lymph nodes were determined and correlated with survival. After neoadjuvant radiochemotherapy both total lymph node yield (12.9 vs. 21.4, p < 0.0001) and number of tumor-positive lymph nodes (1.0 vs. 2.3, p = 0.014) were significantly lower than after primary surgery plus adjuvant radiochemotherapy. Reduced total lymph node yield in neoadjuvantly treated patients had no prognostic impact, with overall survival of patients with 12 or more lymph nodes the same as that of patients with less than 12 lymph nodes. Overall survival of neoadjuvantly treated patients was significantly influenced by the number of tumor-positive lymph nodes with 5-year-survival rates of 88, 63, and 39% for 0, 1-3, and more than 3 positive lymph nodes (p < 0.0001). The UICC/AJCC criterion of a total lymph node yield of 12 or more should be revised for rectal carcinoma patients.

Patterns of initial recurrence and prognosis after sentinel lymph node biopsy and selective lymphadenectomy for melanoma.

The histologic status of the sentinel lymph node is a highly significant prognostic factor for patients with clinically localized cutaneous melanoma. The patterns of initial treatment failure of patients with positive sentinel lymph node biopsy versus those with negative results have not been well described. The purpose of this study was to determine the relative prognostic importance of sentinel lymph node status and to compare patterns of initial treatment failure and prognosis of node-positive versus node-negative cutaneous melanoma patients staged by sentinel lymph node biopsy and selective lymphadenectomy. The authors reviewed the pertinent demographic and surgical data in a consecutive series of patients with cutaneous melanoma who underwent sentinel lymph node staging of nonpalpable regional nodes. Sentinel lymph node biopsy was performed using a combination of blue dye and radiolocalization. Patients with positive biopsy results underwent selective lymphadenectomy, whereas those with negative results were observed. Site(s) and date(s) of initial recurrence and death were determined, and disease-free and overall survival probabilities were compared between positive and negative groups using the log-rank test and multivariable Cox regression analysis. Between February of 1994 and August of 2000, 408 patients with melanoma underwent sentinel lymph node biopsy to stage 518 regional lymph node basins. Mean Breslow tumor thickness was 2.27 mm (range, 0.2 to 14.0 mm). Eighty-five patients (20.8 percent) had at least one histologically positive sentinel lymph node, and selective lymphadenectomy yielded additional positive lymph nodes in 18 of 84 patients (21.4 percent). Recurrences were noted in 70 patients (17 percent) at a median follow-up period of 31.4 months. Recurrences were more frequent in patients with positive biopsy results (36.5 percent) than in those with negative results (12.1 percent, p < 0.0001). Distant sites of initial recurrence were more likely in the positive group than in the negative group (71 percent versus 49 percent of recurrences, respectively; p = 0.06). The false-negative rate for sentinel lymph node staging was 4.5 percent and overall accuracy was 99 percent compared with clinical follow-up. Disease-free and overall survival correlated significantly with tumor thickness, ulceration, sentinel lymph node status, and the number of tumor-positive lymph nodes (two-sided p < 0.0001 for all comparisons). Multivariable analysis revealed that sentinel lymph node status (p = 0.003), tumor thickness (p = 0.016), ulceration (p = 0.006), and age (p = 0.003) were significant independent predictors of survival for the entire group. Tumor thickness and ulceration were significant predictors of recurrence and survival in sentinel node-negative patients but not in sentinel node-positive patients. Sentinel lymph node histology is possibly the most important negative predictor of early recurrence and survival in patients with American Joint Committee on Cancer stage I and II melanoma. The number of positive lymph nodes provides additional prognostic information. Although sentinel node-negative patients are a prognostically favorable group, various combinations of local and regional recurrences comprise the most common pattern of initial relapse after a negative sentinel lymph node biopsy result.

Tumor-Associated Trypsin Inhibitor (Tati) in Primary Esophageal Carcinoma

Esophageal carcinoma has a catastrophic clinical course with a very low 5 year survival rate of 5%. A circulating tumor marker with good specificity and sensitivity would be useful in the management strategy of the disease. So far, no tumor marker effective in esophageal carcinoma has been identified. Preliminary reports suggest satisfactory positivity rates of tumor-associated trypsin inhibitor (TATI) in esophageal carcinoma. We measured TATI levels in 71 patients with primary squamous cell esophageal carcinoma as well as in 30 tissue samples from both carcinoma and normal esophageal mucosa. Detectable TATI levels were not found in tumor tissue samples. The marker showed significantly higher serum levels in patients than in controls, with an overall positivity rate of 28%. TATI levels were significantly lower in patients with a high number of tumor-positive lymph nodes. No relationship was found between TATI and several other clinical and pathological parameters. High TATI levels correlated with a lower probability of overall survival as well as in cases without clinical evidence of lymph node metastases. TATI did not show any relationship with CEA, TPA, ferritin or SCC. The results of the present study suggest that TATI shows a satisfactory positivity rate in esophageal carcinoma, and TATI levels are related to local disease spread and prognosis.