Vascular endothelial growth factor receptor 2 gene polymorphisms as predictors for tumor recurrence and overall survival in non-small-cell lung cancer.

PURPOSE: VEGFR-2 gene displays several functional germline polymorphisms with impact on VEGFR-2 mediated angiogenesis. Our purpose was to evaluate VEGFR-2 polymorphisms as prognostic markers for tumor recurrence and overall survival (OS) in non-small-cell lung cancer (NSCLC). METHODS: In total, 209 Caucasian patients who had been surgically treated for NSCLC between 1996 and 2010 were included in this study. Genotyping of peripheral blood cells was performed by TaqMan® genotyping assays or polymerase chain reaction for five VEGFR-2 polymorphisms. Chi- square test, Kaplan-Meier estimator, and Cox regression hazard model were used to assess the prognostic value of VEGFR-2 polymorphisms. RESULTS: VEGFR-2+4422 (AC)10-14 polymorphism was identified as a positive prognostic marker for time to metastasis (11/12 vs. 11/11 (AC) repeats: hazard ratio (HR), 0.28; 95% confidence interval (CI), 0.11-0.75; p=0.012) and OS (11/12 vs. 11/11 (AC) repeats: HR, 0.41; 95% CI, 0.21-0.82; p=0.012) in squamous cell carcinoma. For adenocarcinoma, VEGFR-2-906 C>T (C/T vs. CC: HR, 0.19; 95% CI, 0.43-0.82; p=0.027) and VEGFR-2-271 G>A (G/A vs. G/G: HR, 0.25; 95% CI, 0.07-0.86; p=0.027) predicted longer time to local recurrence and VEGFR-2-906 C>T was a predictor for better OS (T/T vs. C/C: HR, 0.28; 95% CI, 0.09-0.84; p=0.024). CONCLUSIONS: VEGFR2 germline polymorphisms predict tumor recurrence and OS in NSCLC.

Lymphatic invasion predicts survival in patients with early node-negative non-small cell lung cancer.

OBJECTIVE: The aim of this study was to assess the influence of lymphatic and vascular invasion on overall survival in patients with surgically resected non-small cell lung cancer (NSCLC) without lymph node and distant metastases. METHODS: From January 1999 to December 2009, a total of 190 NSCLC patients with node-negative pT1-pT4 disease underwent radical resection with lymphadenectomy. Pathologic reports were reclassified to the TNM-7 version, and the influence of lymphatic and vascular invasion on overall survival was examined using Kaplan-Meier and adjusted Cox proportional hazards analyses. RESULTS: Lymphatic invasion was present in 34 (17.9%) and vascular invasion in 28 (14.7%) of 190 cases. Lymphatic and vascular invasions were correlated with higher Union for International Cancer Control stages (P = .056 and P = .011, respectively) and poor differentiated tumors (P = .051 and P = .012, respectively). There was no difference between pT1a and pT1b tumors in the presence of lymphatic (P = .912) or vascular (P = .134) invasion. Survival analyses revealed lymphatic (P < .001) and vascular (P = .008) invasion as statistically significant for the entire study population. Multivariable Cox analysis adjusted for age, Union for International Cancer Control stage, and lymphatic and vascular invasion confirmed lymphatic, but not vascular, invasion as an independent prognostic factor (P < .001; hazard ratio, 3.002; 95% confidence interval, 1.780-5.061). Especially in early stages, lymphatic invasion was associated with poorer overall survival in pT1a (P < .001), pT1b (P = .019), and pT2a (P = .028) tumors. CONCLUSIONS: Lymphatic invasion represents an independent risk factor for node-negative NSCLC. Its implications on therapy decision making should be further evaluated, especially in early stages.

PTEN deletion is rare but often homogeneous in gastric cancer.

BACKGROUND AND AIM: Gastric carcinoma is the second most frequent cause of cancer-related death worldwide. As PTEN is a potential modifier of tumour response to trastuzumab, a recently approved therapy in metastatic HER2 positive gastric cancer, the existence of PTEN deletions in primary gastric cancer was investigated. METHODS: 230 primary gastric cancers were analysed in a tissue microarray format by dual labelling fluorescence in situ hybridisation for PTEN deletion. HER2 analysis was also performed. To study PTEN deletion heterogeneity, all available large tissue sections from primary cancer and corresponding metastases were analysed in seven patients. RESULTS: Eight of 180 interpretable primary gastric cancer spots showed PTEN deletions (4.4%), including seven hemizygous and one homozygous deletion. PTEN deletion was correlated with nodal (8 of 122 cases (6.6%); p=0.041) and distant metastases (4 of 19 (21.1%); p<0.001). Large section validation showed a homogeneous distribution of PTEN deletion. HER2 positivity was seen in one PTEN deleted case. CONCLUSION: Genomic PTEN deletion is a rare event in gastric adenocarcinoma but correlates with metastatic disease. The homogeneous distribution pattern indicates that this alteration occurs early in tumour development.