Prognostic significance of pretreatment lymphocyte percentage and age at diagnosis in patients with locally advanced cervical cancer treated with definite radiotherapy

OBJECTIVE: This study aimed to evaluate the prognostic impact of age at diagnosis, and pretreatment hematologic markers, including lymphocyte percentage and the neutrophil-to-lymphocyte ratio (NLR), in patients with locally advanced cervical cancer (LACC) treated with definitive radiotherapy (RT). METHODS: A total of 392 patients with LACC (stage IIb to IVa) treated with cisplatin-based concurrent chemoradiotherapy or RT alone between 2001 and 2012 were retrospectively enrolled. Clinical data and pretreatment complete blood counts were extracted from electronic medical records of the patients, and analyzed. Treatment outcomes, progression-free survival (PFS), and overall survival (OS) were evaluated. RESULTS: Low lymphocyte percentage and a high NLR were associated with younger age, advanced stage, larger tumor size, lymph nodes metastasis, and treatment failure. The cut-off value for lymphocyte percentage and NLR was determined using a receiver operating characteristic curve. In univariate analysis, low lymphocyte percentage (≤24%) was associated with poor PFS and OS, while high NLR ( > 2.8) was significantly associated only with PFS. In multivariate analysis, both lymphocyte percentage (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.40–0.85; P=0.005) and NLR (HR, 1.55; 95% CI, 1.07–2.25; P=0.022) had independent prognostic value for PFS. Compared to younger patients (age ≤50 years), older patients (age > 60 years) had a lower risk of death. CONCLUSION: Although the lymphocyte percentage did not remain significant in multivariate analysis for OS, it was predictive of PFS and OS. Thus, lymphocyte percentage is a simple hematologic parameter with a significant prognostic value in patients with LACC treated with definitive RT.

Epigenetic inactivation of RUNX3 in colorectal cancer

PURPOSE: Emerging evidence indicates that runt-related transcription factor 3 (RUNX3) is an important tumor suppressor gene in several cancer types, including colorectal cancer (CRC). However, the clinical significance of RUNX3 inactivation in CRC remains unclear. The aim of this study was to examine the correlation between clinicopathologic factors and RUNX3 hypermethylation/expression in CRC. METHODS: Sixty-two CRC patients who were treated at the Soonchunhyang University College of Medicine were recruited in this study. The hypermethylation of CpG islands in the RUNX3 promoter and the expression of RUNX3 mRNA were identified by methylation-specific polymerase chain reaction (PCR) and reverse transcriptase-PCR, respectively. The expression of RUNX3 was determined by immunohistochemical staining. RESULTS: Of the 62 CRC tissue samples, 20 (32.3%) presented hypermethylated RUNX3 promoters. Aberrant RUNX3 hypermethylation was found to be associated with vascular (P = 0.006) and lymphatic (P = 0.002) invasion. Hypermethylation of RUNX3 was associated with poor survival outcomes (P = 0.038). However, expression of RUNX3 was not a prognostic factor (P = 0.363). CONCLUSION: Hypermethylation of RUNX3 may be a predictor of a poor prognosis in CRC.

Association Between c-Met and Lymphangiogenic Factors in Patients With Colorectal Cancer

PURPOSE: Animal models show a strong relationship between lymphangiogenesis and lymph node metastasis. However, the clinical significance of lymphangiogenesis in patients with colorectal cancer (CRC) remains uncertain. This study aimed to evaluate the association between c-Met and lymphangiogenic factors and to elucidate the prognostic significance of c-Met in patients with CRC. METHODS: A total of 379 tissue samples were obtained from surgically resected specimens from patients with CRC at Soonchunhyang University Cheonan Hospital between January 2002 and December 2010. The expressions of c-Met, vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3, and podoplanin were examined using immunohistochemistry. The expression of c-Met and clinical factors were analyzed. RESULTS: Of the 379 tissues, 301 (79.4%) had c-Met expression. High expression of c-Met in tumor cells was significantly associated with high expression of VEGF-C (P < 0.001) and VEGFR-3 (P = 0.001). However, no statistically significant association with podoplanin (P = 0.587) or VEGF-D (P = 0.096) was found. Of the 103 evaluable patients, expression of c-Met in tumor cells was significantly associated with advanced clinical stage (P = 0.020), positive lymph node status (P = 0.038), and high expression of VEGF-C (P = 0.020). However, no statistically significant association with podoplanin (P = 0.518), VEGFR-3 (P = 0.085), VEGF-D (P = 0.203), or overall survival (P = 0.360) was found. CONCLUSION: Our results provide indirect evidence for an association and possible regulatory link of c-Met with the lymphangiogenic markers, but c-Met expression in patients with CRC is not a prognostic indicator for overall survival.

CORRIGENDUM: Correction of funding statement in ACKNOWLEDGEMENTS section: Epigenetic inactivation of RUNX3 in colorectal cancer

Correction of funding statement in ACKNOWLEDGEMENTS section.

Astrocyte elevated gene-1 overexpression in hepatocellular carcinoma: an independent prognostic factor

PURPOSE: Astrocyte elevated gene-1 (AEG-1) plays important roles in tumorigenesis such as proliferation, invasion, metastasis, angiogenesis, and chemoresistance. We examined the expression of AEG-1 in patients with hepatocellular carcinoma (HCC). METHODS: Eighty-five samples were collected from patients with HCC who underwent surgery and were histopathologically confirmed to have HCC. Two independent pathologists, experienced in evaluating immunohistochemistry and blinded to the clinical outcomes of the patients, reviewed all samples. They determined AEG-1 expression semiquantitatively by assessing the percentage of positively stained immunoreactive cells and staining intensity. Clinicopathological data were analyzed in association with prognosis. RESULTS: The association was estimated by univariate and multivariate analyses with Cox regression. Tumor size (hazard ratio [HR], 2.285; 95% confidence interval [CI], 1.175-4.447; P = 0.015), microvascular invasion (HR, 6.754; 95% CI, 1.631-27.965; P = 0.008), and AEG-1 expression (HR, 4.756; 95% CI, 1.697-13.329; P = 0.003) were independent prognostic factors for overall survival. Those for disease-free survival rate were tumor size (HR, 2.245; 95% CI, 1.282-3.933; P = 0.005) and AEG-1 expression (HR, 1.916; 95% CI, 1.035-3.545; P = 0.038). The cumulative 5-year survival and recurrence rates were 89.2% and 50.0% in the low-expressing group and 24.5% and 82.4% in the high-expressing group, respectively. CONCLUSION: The results suggest that AEG-1 overexpression could serve as a valuable prognostic marker in patients with HCC.

Detection of BRAFV600E Mutations in Papillary Thyroid Carcinomas by Peptide Nucleic Acid Clamp Real-Time PCR: A Comparison with Direct Sequencing

BACKGROUND: Papillary thyroid carcinoma (PTC) of the thyroid is the most common endocrine malignancy. High prevalence of an activating point mutation of BRAF gene, BRAFV600E, has been reported in PTC. We assessed the efficiency of peptide nucleic acid clamp real-time polymerase chain reaction (PNAcqPCR) for the detection of BRAFV600E mutation in PTC in comparison with direct sequencing (DS). METHODS: A total of 265 thyroid lesions including 200 PTCs, 5 follicular carcinomas, 60 benign lesions and 10 normal thyroid tissues were tested for BRAFV600E mutation by PNAcqPCR and DS. RESULTS: The sensitivity and accuracy of the PNAcqPCR method were both higher than those of DS for the detection of the BRAFV600E mutation. In clinical samples, 89% of PTCs harbored the BRAFV600E mutation, whereas 5 follicular carcinomas, 50 benign lesions and 10 normal thyroid tissues lacked the mutation. The mutation was associated with aggressive clinical behaviors as extrathyroid invasion (p=0.015), lymph node metastasis (p=0.002) and multiple tumor numbers (p=0.016) with statistical significance. CONCLUSIONS: The PNAcqPCR method is efficiently applicable for the detection of the BRAFV600E mutation in PTCs in a clinical setting.