Metastatic Lymph Node Ratio (mLNR) is a Useful Parameter in the Prognosis of Colorectal Cancer; A Meta-Analysis for the Prognostic Role of mLNR.

Background and objectives: The presenting study aimed to elucidate the prognostic role of the metastatic lymph node ratio (mLNR) in patients with colorectal cancer (CRC), using a meta-analysis. Materials and Methods: Using data from 90,274 patients from 14 eligible studies, we performed a meta-analysis for the correlation between mLNR and survival rate. Besides, subgroup analyses were performed, based on tumor stage, tumor location, and mLNR. Results: A high mLNR showed significant correlation with worse overall survival and disease-free survival rates in CRC patients (hazard ratio (HR), 1.617, 95% confidence interval (CI) 1.393-1.877, and HR 2.345, 95% CI 1.879-2.926, respectively). In patients with stage III, who had regional LN metastasis, the HRs were 1.730 (95% CI 1.266-2.362) and 2.451 (95% CI 1.719-3.494) for overall and disease-free survival, respectively. According to tumor location, rectal cancer showed a worse survival rate when compared to colon cancer. In the analysis for overall survival, when mLNR was 0.2, HR was the highest across the different subgroups (HR 5.040, 95% CI 1.780-14.270). However, in the analysis for disease-free survival, the subgroup with an mLNR < 0.2 had a higher HR than the other subgroups (HR 2.878, 95% CI 1.401-5.912). Conclusions: The mLNR may be a useful prognostic factor for patients with CRC, regardless of the tumor stage or tumor location. Further studies are necessary for the detailed criteria of mLNR before its application in daily practice.

Gland Attenuation, a Novel Morphological Feature of Colorectal Cancer: Evidence for an Epithelial-Mesenchymal Transition.

PURPOSE: Along the invasive margin, colorectal cancer may show distinctive morphologic changes characterized by an asymmetrically attenuating tumor gland with loss of polarity. The author coined the term 'gland attenuation (GA)' for these peculiar changes. The aims of this study were to compare the immunoreactivity of the epithelial-mesenchymal transition (EMT) markers E-cadherin and ß-catenin and thus determine whether EMTs occurs at tumor budding (TB) or GA sites and to assess the association of TB and/or GA levels with clinicopathological parameters and prognosis. METHODS: Expression patterns of E-cadherin and ß-catenin in the tumor centers at GA and TB sites were examined in 101 patients with well or moderately differentiated CRCs, and the prognostic significance of TB and/or GA was statistically evaluated. RESULTS: GA foci, as well as TB foci, revealed loss of membranous and cytoplasmic E-cadherin expressions and aberrant ß-catenin expression with reduced membranous expression and increased localization to the nucleus, suggesting that EMTs occur in GA as well as in TB. The high-TB and the TB-dominant groups were significantly correlated with advanced invasion depth, presence of lymph node metastasis, advanced pathologic staging and presence of lymphovascular invasion. The high-TB and the TB-dominant groups showed poor overall survival (OS) and recurrence-free survival (RFS), and high TB was an independent prognostic factor in the multivariate analyses for OS and RFS. CONCLUSION: This study showed evidence that EMTs occurs at GA sites as well as TB foci. TB is a strong and independent prognostic factor, and TB-dominance may be an indicator of adverse clinical outcome.

Difference of the Nuclear Green Light Intensity between Papillary Carcinoma Cells Showing Clear Nuclei and Non-neoplastic Follicular Epithelia in Papillary Thyroid Carcinoma.

BACKGROUND: There is subjective disagreement regarding nuclear clearing in papillary thyroid carcinoma. In this study, using digital instruments, we were able to quantify many ambiguous pathologic features and use numeric data to express our findings. METHODS: We examined 30 papillary thyroid carcinomas. For each case, we selected representative cancer cells showing clear nuclei and surrounding non-neoplastic follicular epithelial cells and evaluated objective values of green light intensity (GLI) for quantitative analysis of nuclear clearing in papillary thyroid carcinoma. RESULTS: From 16,274 GLI values from 600 cancer cell nuclei and 13,752 GLI values from 596 non-neoplastic follicular epithelial nuclei, we found a high correlation of 94.9% between GLI and clear nuclei. GLI between the cancer group showing clear nuclei and non-neoplastic follicular epithelia was statistically significant. The overall average level of GLI in the cancer group was over two times higher than the non-neoplastic group despite a wide range of GLI. On a polygonal line graph, there was a fluctuating unique difference between both the cancer and non-neoplastic groups in each patient, which was comparable to the microscopic findings. CONCLUSIONS: Nuclear GLI could be a useful factor for discriminating between carcinoma cells showing clear nuclei and non-neoplastic follicular epithelia in papillary thyroid carcinoma.

Gender differences in the association between socioeconomic status and hypertension incidence: the Korean Genome and Epidemiology Study (KoGES).

BACKGROUND: Hypertension is a leading cause of cardiovascular events. We examined whether there was a gender difference in the association between SES, measured by education and income, and hypertension incidence. METHODS: Data for 2596 men and 2686 women aged 40-69 years without hypertension at baseline from the Korean Genome and Epidemiology Study (KoGES) were analyzed. Participants had two follow-up examinations during 4 years, and were classified into three categories by self-reported educational attainment: ≥ 10 years, 7-9 years, and 0-6 years, and monthly household income (×10,000 Korean Won): ≥ 200, 100-199, and <100. The association between SES and incidence hypertension was examined by Cox's proportional hazard regression analyses. RESULTS: Adjusting for conventional risk factors, compared with the high education group (reference), the hazard ratios (95% confidence interval) for incident hypertension across the education categories were 1.54 (1.16-2.06) and 1.80 (1.36-2.38) in women and 1.15 (0.92-1.43), and 1.08 (0.84-1.38) in men. Women with the low household income were more likely to have hypertension than those with the high household income and incident hypertension had an inverse association with household income level in women: multivariate adjusted hazard ratios were 1.00 (reference), 1.10 (0.83-1.45), and 1.63 (0.75-2.16). Men with medium income were less likely to have hypertension compared with those with high income (0.76, 0.61-0.90). CONCLUSIONS: Educational level and economic status had stronger impacts on hypertension in Korean women than men. Thus, a stratified approach for women of low socioeconomic status, especially those with low educational attainment, is needed for the prevention of hypertension.

Anthropometric indices as predictors of hypertension among men and women aged 40-69 years in the Korean population: the Korean Genome and Epidemiology Study.

BACKGROUND: Obesity is one of the most significant risk factors for hypertension. However, there is controversy regarding which measure is the best predictor of hypertension risk. We compared body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) in subjects as predictive indicators for development of hypertension. METHODS: The data were obtained from the Korean Genome and Epidemiology Study (KoGES), a large population-based prospective cohort study. A total of 4,454 subjects (2,128 men and 2,326 women) aged 40-69 years who did not have hypertension at baseline were included in this study. Incident hypertension was defined as systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or anti-hypertensive medication use during the 4-year follow up. Receiver operating characteristic (ROC) analysis was used to compare discrimination abilities for anthropometric indices for hypertension. Hazard ratios were calculated by Cox proportional hazard model with adjustment for age, smoking status, alcohol consumption, diabetes and family history of hypertension by sexes. RESULTS: In men, the area under the ROC curve (AROC) was 0.62 for WC, WHR, and WHtR and 0.58 for BMI. In women, the AROCs for BMI, WC, WHR, and WHtR were 0.57, 0.66, 0.68, and 0.68, respectively. After adjustment for risk factors, a 1 standard deviation increase in BMI, WC, WHR, WHtR were significantly related to incident hypertension, respectively (hazard ratio: 1.39, 1.50, 1.40 and 1.49 in men, 1.31, 1.44, 1.35 and 1.48 in women). CONCLUSIONS: The central obesity indices WC, WHR, and WHtR were better than BMI for the prediction of hypertension in middle-aged Korean people. WHtR facilitates prediction of incident hypertension because of the single standard regardless of sex, ethnicity, and age group. Therefore, WHtR is recommended as a screening tool for the prediction of hypertension.

Age at menarche and its association with dysglycemia in Korean middle-aged women.

OBJECTIVE: Recent studies have demonstrated that earlier menarche is associated with increased risks of prediabetes and diabetes in white women; however, the associations have not been fully explored in Asian populations. We investigated the associations between age at menarche and prediabetes and/or diabetes in Korean middle-aged women. METHODS: This was a cross-sectional study of 2,039 premenopausal and postmenopausal women aged 44 to 56 years who visited the health promotion center for medical checkups. Participants were divided into three groups based on age at menarche: early (<13 y), average (13-16 y), and late (>16 y). RESULTS: The mean (SD) age at menarche was 14.6 (1.6) years. Of 2,039 women, 820 and 85 women had prediabetes (impaired fasting glucose and/or 5.7%-6.4% glycated hemoglobin) and diabetes, respectively. On logistic regression analysis, earlier menarche was significantly associated with prediabetes (odds ratio [OR], 1.80; 95% CI, 1.24-2.61; P = 0.002), diabetes (OR, 2.43; 95% CI, 1.04-5.69; P = 0.04), and dysglycemia (OR, 1.85; 95% CI, 1.28-2.66; P = 0.001), after adjusting for a number of confounding factors, compared with average age at menarche. On linear regression analysis, earlier age at menarche was significantly associated with increased fasting insulin, homeostatic model assessment for insulin resistance, homeostatic model assessment for ß-cell function, body mass index, and waist circumference. CONCLUSIONS: Age at menarche is inversely associated with various forms of dysglycemia. A history of earlier menarche may be helpful in predicting prediabetes and subsequent diabetes in Korean women.

Expression of HuR and Cyclooxygenase-2 in Nodular Fasciitis and Low-Grade Sarcoma: An Immunohistochemical Study.

BACKGROUND: Nodular fasciitis is the most common reactive mesenchymal lesion to be misidentified as a type of sarcoma. HuR is an mRNA-binding protein that can stabilize cyclooxygenase-2 (COX-2) mRNA leading to COX-2 overexpression. The aim of this study is a comparison of the expressions of COX-2 and HuR and the relationships between their expressions and the clinicopathological parameters in nodular fasciitis and low-grade sarcoma. METHODS: We measured the expression of HuR and COX-2 in 21 cases of nodular fasciitis and 37 cases of low-grade sarcoma using immunohistochemistry. RESULTS: The frequency of cytoplasmic immunoreactivity for HuR was 5 of 21 cases of nodular fasciitis (23.8%) and 23 of 37 cases of low-grade sarcoma (62.1%) (p=.013). COX-2 expression was moderate or strong in nodular fasciitis (12/21, 57.1%) and in low-grade sarcoma (29/37, 78.4%) (p=.034). In addition, a significant difference existed between these two entities in terms of the relationship between moderate or strong COX-2 expression and HuR cytoplasmic immunoreactivity (p=.009). Moderate or strong COX-2 immunoreactivity correlated with nuclear (p=.016) or cytoplasmic HuR (p=.024) expression in low-grade sarcoma but not in nodular fasciitis. CONCLUSIONS: This study suggests that HuR and COX-2 expression may be useful to differentiate nodular fasciitis from low-grade sarcoma.

Collagen triple helix repeat containing-1 (CTHRC1) expression in invasive ductal carcinoma of the breast: the impact on prognosis and correlation to clinicopathologic features.

CTHRC1 has been known as a regulator of collagen expression and cell migration. The aim of this research was to clarify the clinicopathologic significance of CTHRC1 expression in human breast cancer. 22 cases of breast cancer tissues, randomly selected from clinically diagnosed patients, showed a significant increase of CTHRC1 mRNA expression compared to the normal tissue from the same patients using RT-PCR and real-time PCR. Additionally we investigated breast cancers from 189 patients by immunohistochemistry (IHC). A high level of CTHRC1 expression was observed in 111 (58.7 %) out of 189 breast cancer patients and the expression was significantly correlated with histologic grade (P = 0.026), nodal status (P < 0.001), and TNM pathologic stage (P = 0.002). High CTHRC1 expression was associated with a shorter recurrence free survival (P = 0.008). Taken together, the results showed that CTHRC1 over-expression was significantly associated with clinicopathological factors of poor prognosis in invasive ductal carcinoma. CTHRC1 could be used as a supplementary prognostic biomarker and a potential therapeutic target in breast cancer.