Paired Metastatic Lymph Nodes Research Articles

High epidermal growth factor receptor expression in metastatic lymph nodes may be more prognostic than in primary tumor for colorectal cancer survival

15031 Background: High epidermal growth factor receptor (EGFR) expression in the primary tumor is prognostic for poor survival in colorectal cancer (CRC). Discordance of EGFR expression has been noted in the paired primary versus nodal or distant metastasis. The aim of this study was to evaluate prognostic value of elevated EGFR expression in nodal or distant metastasis versus primary tumor tissue. Methods: Tissue microarrays from 93 surgically resected CRC primaries were analyzed for EGFR expression using immunohistochemistry along with 49 paired metastatic lymph nodes (MLN) and 19 distant metastases. Logistic regression, Kaplan-Meier survival curves, and the log-rank test were used to describe the association of tumor stage and survival with EGFR level dichotomized to low expression (0,1) versus high expression (2,3). Results: High EGFR expression in primary tumor, MLN and distant metastasis were 18%, 24%, and 21% respectively. In stage III/IV patients, eight of 14 patients (57%) with EGFR+ primary tumors did not show high expression in MLN, and 6/35 (17%) patients with EGFR- primary tumors gained high EGFR expression in MLN. High EGFR expression in primary tumor was associated with stage III/IV versus stage I/II disease (odds ratio 5.5, P = 0.012) and therefore predicted poor survival (P = 0.046). High EGFR expression in the primary or in distant metastasis was not associated with poor survival, whereas only high EGFR expression in MLN was associated with poor survival in stage III and stage IV disease combined or separately (Table 1) Conclusions: High EGFR expression in MLN appears more accurate in predicting survival than its expression in the primary or distant metastasis, thus may aid in selecting patients to receive adjuvant treatment incorporating anti-EGFR therapy. Prognostic values of discordant EGFR expression in different tissues warrants further investigation. Log rank P-values comparing overall survival for high EGFR expression in primary and metastatic tis Stage III/IV(n=49) Stage III(n=30) Stage IV(n=19) Pirmary tumor 0.332 0.795 0.161 Metastastic lymph node 0.005 0.002 0.014 Distant metastasis 0.246 No significant financial relationships to disclose.

The study of p16 and p15 gene methylation in head and neck squamous cell carcinoma and their quantitative evaluation in plasma by real-time PCR

Epigenetic silencing of the p16 and p15 genes by promoter methylation are commonly observed in human epithelial malignancies, including head and neck squamous cell carcinomas (HNSCC). In this study, a methylation-specific polymerase chain reaction (MSP) was used to evaluate the methylation status of the p16 and p15 genes in 73 HNSCC surgical specimens. p16 and p15 gene methylation was also examined in 29 paired metastatic lymph nodes and 29 paired histologically, normal resection margin mucosae. The quantity of cell-free methylated p16 and p15 DNA in the plasma samples of 20 HNSCC patients and 24 healthy controls was also examined using a fluorescence-based real-time PCR assay. The frequencies of p16 and p15 methylation in the primary tumour were 49% and 60%, respectively. Concordant methylation of p16 and p15 in tumour samples and metastatic lymph nodes was found in 59 and 38% of cases, respectively. A significantly higher prevalence of p15 methylation was found in histologically-normal surgical margin epithelia of HNSCC patients with chronic smoking and drinking habits compared with non-smokers and non-drinkers. In addition, methylated p16 and p15 DNA levels were significantly higher in the plasma of HNSCC patients (mean 56 copies/ml plasma and 65 copies/ml plasma, respectively) compared with normal controls (mean 6 copies/ml plasma and 16 copies/ml plasma, respectively). In conclusion, promoter methylation of the p16 and p15 genes is involved in the pathogenesis of HNSCC and may be related to chronic smoking and drinking. The differential levels of methylated p16 and p15 DNA in plasma might be potential useful markers in screening high-risk populations for early HNSCC and monitoring their treatment response.

EGFR, c-erbB2 and p53 protein in the primary lesions and paired metastatic regional lymph nodes in breast cancer

Aims: Various biological parameters are now being evaluated as predictors for the response of chemohormonal therapy for breast cancer. Few studies compare these parameters between the primary lesions and metastatic regional lymph nodes of breast cancer.Methods: Immunohistochemical analyses for epidermal growth factor receptor (EGFR), c-erbB2 and p53 protein were performed on the primary lesions and matching metastatic regional lymph nodes of 107 breast cancers. The intensity of the immunoreactivity was graded for heterogeneous or 10–50% staining, and diffuse or >50% staining.Results: EGFR, c-erbB2 and p53 protein showed a concordance between the primary lesions and matching regional lymph nodes in terms of a negative or positive finding (+ and ++) in 98 (92%) of 106 cases, 76 (100%) of 76 cases and 79 (93%) of 85 cases respectively, while EGFR, c-erbB2 and p53 protein also showed a concordance in the intensity of the immunoreactivity in 24 (89%) of 27 cases 14 (74%) of 19 cases and 30 (94%) of 32 cases respectively. In 21 of 24 cases which showed a disconcordance in the positivity or the intensity of the positivity of EGFR, c-erbB2 and p53 protein, one of the primary lesions and matching regional lymph nodes showed heterogeneous or 10–50% immunostaining.Conclusions: The immunoreactivity of EGFR, c-erbB2 and p53 protein shows a concordance between the primary lesions and matching metastatic regional lymph nodes in a majority of breast cancers.

Expression of urokinase-type plasminogen activator, its receptor, and its inhibitor in gastric adenocarcinoma tissues.

The plasminogen and plasmin system, which is mainly regulated by urokinase-type plasminogen activator (uPA), its receptor (uPAR) and its inhibitor (PAI-1), is generally believed to play a role in cancer invasion and metastasis. This study was conducted to investigate the role of uPA, uPAR and PAI-1 in the invasion and metastasis of gastric adenocarcinoma. The expression of mRNAs for uPA and PAI-1 was determined by Northern blot analysis in nine primary gastric cancer tissues, nine paired metastatic lymph nodes and normal gastric mucosa. The mRNA of uPA was not or faintly detected in normal mucosa, while the expression was increased in both primary gastric cancer tissues and metastatic lymph nodes to a similar degree. The mRNA expression for PAI-1 in the gastric cancer tissues was not different from that in the paired metastatic lymph nodes and normal mucosae. uPAR was determined by immunohistochemical staining, demonstrating that five (56%) and six (67%) out of nine primary gastric cancer tissues and nine paired metastatic lymph nodes were positive, respectively and the intensity was stronger in metastatic lymph nodes. The results support the concept that most gastric cancer cells may have an innately moderate level of uPA and uPAR, and that increase of uPAR expression can be considered to be closely associated with cancer invasion and metastasis.