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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 β-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 β-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 β-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.

Diabetes is an increasing global health and economic problem.1 Upon diagnosis of diabetes (even prediabetes), some individuals already experience various complications including microvascular and macrovascular complications.2-4 Thus, it has become more important to identify individuals at risk for diabetes earlier in life so that they may benefit from early intervention. Age at menarche has been suggested to be associated with future risk of adverse health consequences, including higher body mass index (BMI),5 metabolic syndrome,6 cardiovascular disease,7 and mortality.7,8 A series of studies have shown an inverse correlation between age at menarche and risk of diabetes.9-13 However, relatively few inconsistent results on the association between age at menarche and prediabetes have been reported.11,14 In addition, most studies reporting an association on these issues have been conducted in western countries, whereas the association remains unclear in nonwhite populations, including Asian populations. The mechanisms that underlie these connections have yet to be fully identified. Studies have demonstrated associations between earlier age at menarche and elevated fasting glucose, fasting insulin, and insulin resistance5,8; however, the results have been inconclusive. Furthermore, some studies have suggested that the association between age at menarche and diabetes is completely mediated by obesity,9,10 whereas other studies have found no such relationship.11,12 Therefore, these issues must be revisited. In this study, we determined whether there was an independent association between age at menarche and prediabetes or diabetes, and we clarified if these associations were mediated by adiposity in Korean women.

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.

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.

Background: There is a subjective disagreement about nuclear chromatin in the field of patholo gy. Objective values of red, green, and blue (RGB) light intensities for nuclear chromatin can be obtained through a quantitative analysis using digital images. Methods: We examined 10 cases of well differentiated neuroendocrine tumors of the rectum, small cell lung carcinomas, and moderately differentiated squamous cell lung carcinomas respectively. For each case, we selected 30 representative cells and captured typical microscopic findings. Using an image analyzer, we de termined the longest nuclear line profiles and obtained graph files and Excel data on RGB light intensities. We assessed the meaningful differences in graph files and Excel data among the three different tumors. Results: The nucleus of hematoxylin and eosin-stained tumor cells was expressed as a combination of RGB light sources. The highest intensity was from blue, whereas the lowest intensity was from green. According to the graph files, green showed the most noticeable change in the light intensity, which is consistent with the difference in standard deviations. Conclusions: The change in the light intensity for green has an important implication for differentiating between tumors. Specific features of the nucleus can be expressed in specific values of RGB light intensities.

Background Malignant lymphomas are classified on the basis of morphology, immunohistochemistry, and genetic and molecular biological features. Morphology is considered the most important and basic feature. Lymphomas can be classified as small, medium, or large depending on the cell size, but this criterion tends to be rather subjective. The aim of this study was to investigate the usefulness of an objective approach based on quantitative measurements. Methods Twenty specimens of mantle cell lymphoma and 2 specimens of the tonsil were examined. The nuclear area of 6,401 tumor cells of mantle cell lymphoma and 743 normal mantle cells of reactive tonsils were measured by 3 authors by using a user-controlled image-analyzer. The images of the nuclei were outlined using the spline method and the i-solution software, and the data were assessed using ANOVA and Student's t-test. Results The mean nuclear areas of mantle cell lymphoma cells measured by the 3 authors were 37.9 [7.9] µm2, 37.9 [7.2] µm2, and 38.2 [7.7] µm2 and those of normal mantle cells in reactive tonsil were 28.6 [2.3] µm2, 28.8 [2.0] µm2, and 27.0 [3.0] µm2. There was no statistical difference between the 3 observations of mantle cell lymphoma (P=0.580) and normal tonsils. Conclusion For morphology, nuclear area is considered an important feature in the classification schemes of lymphoma. We showed that nuclear area measurement by using image analyzer can be used as an objective quantitative method. We think that nuclear morphometry may play a significant role in the diagnosis of lymphoma.

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 (x10,000 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.

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.

Background: Decay accelerating factor (DAF/CD55), regulates the complement system by accelerating decay of the C3 convertase, has been described in several malignancies, however, the clinicopathologic significance of CD55 and its receptor CD97 has not been fully investigated. We examined the expression patterns of both CD55 and CD97 and their association with clinicopathologic parameters in colorectal cancers (CRCs). Methods: Expression patterns of CD55 and CD97 in the stroma and tumor cells at tumor center and invasive front were examined in 130 CRCs, and their significance was statistically evaluated. Results: CD55-high stroma was correlated with tumor border (p= 0.006) and invasion depth (p= 0.013). CD55-high tumor cells at tumor center and invasive front were correlated with histologic grade, and CD55-high tumor cells at invasive front with tumor, node and metastasis (TNM) stage (p < 0.05). CD97-high stroma was correlated with lymph node metastasis (p= 0.016) and TNM stage (p= 0.030). CD97-high tumor cells at tumor center and invasive front were correlated with tumor size and CD97-high tumor cells at tumor center with tumor border (p< 0.05). Patients with CD55-high stroma showed poor overall and recurrence-free survival (p< 0.05) in univariate analysis, and were independently associated with short recurrence-free survival (p= 0.025) in multivariate analysis. Conclusions: Stromal CD55 overexpression would be an indicator of adverse clinical outcome and a useful prognostic factor.

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.