High-sensitivity C-reactive Protein and Regression of Low-grade Squamous Intraepithelial Lesion: The Role of Low-grade Inflammation in Cervical Carcinogenesis.

BACKGROUND: Inflammation is emerging as a potential mechanism of cervical carcinogenesis. However, few studies have investigated the association between host inflammatory status and the natural course of cervical precursor lesion. The aim of this study was to assess the probability of LSIL regression, associated with an inflammatory biomarker, high-sensitivity C-reactive protein (hs-CRP). METHODS: In a longitudinal cohort study, female participants were examined annually or biannually using cervical cytology between 2006 and 2015. Incident LSIL cases were included in the analysis, with regression defined as at least one consecutive normal cytologic result. A total of 520 women aged 22-64 years were followed up for LSIL regression. The multivariable-adjusted hazard ratios (HRs) for LSIL regression were estimated using a parametric proportional hazards model. RESULTS: During 827.5 person-years of follow-up, 486 out of 520 subjects (93.5%) showed LSIL regression. After adjusting several important potential confounders, a higher quartile of hs-CRP levels was significantly associated with a lower rate of regression (for quartile 4 vs quartile 1, inverse HR 1.33; 95% CI, 1.04-1.69; P for trend = 0.028). CONCLUSIONS: The low rate of spontaneous regression recorded in women with higher hs-CRP lends support to the role of the perturbated host inflammatory status in cervical carcinogenesis, and suggests that hs-CRP level could help monitor LSIL.

Clinicopathologic characteristics of early gastric cancer according to specific intragastric location.

BACKGROUND: Although the incidence of early gastric cancer (EGC) continues to rise, there have been few studies on the intra-gastric distribution and locational characteristics of EGCs. In addition, there has been no attempt to visualize the intra-gastric distribution of EGCs using a merged tumor map. METHODS: We investigated the anatomic distribution of 644 cases of EGCs and analyzed the correlation between clinicopathologic findings and location by dividing areas of the stomach vertically and transversely. Merged tumor maps were generated using 310 surgically resected cases. RESULTS: Early gastric cancer was most commonly located in the antrum (57.5%) along the lesser curvature (37.8%). The intra-gastric distributions were similar in the merged tumor maps. Vertically, cancers of the middle third were associated with younger patient age, larger tumor size, and more frequent poorly differentiated (PD) or signet ring cell histology than cancers in other sites. Submucosal invasion was most frequently observed in the upper third. When divided transversely, tumors in the anterior or posterior wall showed more frequent PD or signet ring cell histology than those along the lesser or greater curvatures. CONCLUSIONS: EGC is the most prevalent in the antrum along the lesser curvature and has characteristic locational features, including histologic type, invasion depth, patient age, and tumor size. These results will improve the endoscopic detection rate of EGC and help to determine endoscopic resectability.

Expression Pattern of Smad4/GATA3 as a Predictor of Survival in Invasive Ductal Carcinoma of the Breast.

BACKGROUND: Smad4 and GATA3 proteins are known prognostic markers in various cancers. Smad4 is a mediator linked to both tumour suppression and progression. GATA3 is a regulator of development and morphogenesis of the mammary gland. We assessed and compared the predictive performance of Smad4 and GATA3 for clinical outcomes in patients with breast cancer. METHODS: The combined expression pattern based on Smad4+/- and GATA3+/- was evaluated by immunostaining using breast cancer tissue microarray, and the relationships between protein expression and clinicopathological variables were analysed. RESULTS: Smad4 expression was only associated with an ill-defined tumour border, whereas GATA3 was associated with several good prognostic factors. On analysis of combined markers, there was a significant difference in the expression of fascin (an important factor for cancer invasiveness) between the Smad4+/GATA3- and Smad4-/GATA3+ groups. Smad4+/GATA3- was correlated with worse clinicopathological parameters, relapse-free survival (RFS), and overall survival (OS), compared to Smad4-/GATA3+. CONCLUSION: Combined markers of Smad4/GATA3 showed a superior performance compared to single markers for predicting RFS and OS in patients with breast cancer.

Decreased expression of p27 is associated with malignant transformation and extrathyroidal extension in papillary thyroid carcinoma.

Cell cycle regulatory proteins including p16, p27, and p53 are well studied in various cancers. However, their single or concurrent roles related with the clinicopathological parameters are not clearly recognized. We analyzed the expression of p16, p27, and p53 cell cycle regulatory proteins in papillary thyroid carcinoma (PTC). To determine the prognostic significance of cell cycle regulatory proteins, 107 PTCs were examined. We analyzed the individual expression of p16, p27, and p53 and their concurrent expressions, with the relationship to various clinicopathological parameters including differentiation from benign lesions. High expression of p16 and p53 and low expression of p27 were related with the distinguishing of PTC from benign lesions. In addition, normal thyroidal tissue showed higher p27 expression than nodular hyperplasia. In relation to extrathyroidal extension (ETE), the low expression of p27 was related with the presence of ETE. The low expression of p27 and high expression of p16 and p53 may affect the development of PTC. In addition, low p27 expression is related with the existence of ETE.

Pre- and post-ESD discrepancies in clinicopathologic criteria in early gastric cancer: the NECA-Korea ESD for Early Gastric Cancer Prospective Study (N-Keep).

BACKGROUND: Discrepancies in the clinicopathologic parameters pre- and post-endoscopic submucosal dissection (ESD) sometimes necessitate additional surgical resection. The aim of this study was to assess such discrepancies in clinicopathologic parameters before and after ESD in the context of reducing the risk of failure of curative ESD. METHODS: Data on 712 early gastric cancer patients were prospectively collected from 12 university hospitals nationwide. The inclusion criteria were differentiated carcinoma <3 cm in size, no ulceration, submucosal invasion <500 µm, and no metastasis. Clinicopathologic factors were compared retrospectively. RESULTS: The discrepancy rate was 20.1 % (148/737) and the most common cause of discrepancy was tumor size (64 cases, 8.7 %). Ulceration, undifferentiated histology, and SM2 invasion were found in 34 (4.6 %), 18 (2.4 %), and 51 cases (6.9 %), respectively. Lymphovascular invasion (LVI) was observed in 34 cases (4.6 %). Cases with lesions exceeding 3 cm in size showed more frequent submucosal invasion, an elevated gross morphology, and upper and middle locations (p < 0.05). In the cases with ulceration, depth of invasion (DOI) was deeper than in the cases without ulceration (p = 0.005). Differentiation was correlated with DOI and LVI (p = 0.021 and 0.007). DOI was correlated with tumor size, ulceration, differentiation, LVI, gross type, and location. There were statistically significant differences between mucosal cancer cases and submucosal cancer cases in tumor size, differentiation, ulceration, LVI, and location. CONCLUSIONS: The overall discrepancy rate was 20.1 %. To reduce this rate, it is necessary to evaluate the DOI very cautiously, because it is correlated with other parameters. In particular, careful checking for SM-invasive cancer is required due to the high incidence of LVI irrespective of the depth of submucosal invasion.

Diagnostic and prognostic roles of the mean platelet volume in malignant tumors: a systematic review and meta-analysis.

The aim of this study was to elucidate the diagnostic and prognostic roles of the mean platelet volume (MPV) in various malignant tumors through a systematic review and meta-analysis. The current study included 2,053 patients and 1,396 healthy subjects in 18 eligible studies. We performed a meta-analysis of MPV levels and the mean difference between healthy subjects and pre- and post-treatment patients. Subgroup analysis was conducted based on specific organs and platelet counts. In addition, the correlation between MPV and survival was investigated. The pooled MPVs of healthy subjects, pre-treatment, and post-treatment patients were 8.428 fL (95% confidence interval [CI] 8.118-8.738), 8.831 fL (95% CI 8.582-9.087), and 8.521 fL (95% CI 8.162-8.880), respectively. The mean difference in MPV between healthy subjects and pre-treatment patients was 0.502 (95% CI 0.285-0.719, P < 0.001). However, in lung cancer, the mean difference between pre-treatment patients and healthy subjects was -0.352 (95% CI -0.763-0.060, P = 0.094). The pooled MPV of post-treatment patients was significantly decreased compared to pre-treatment patients. There was no correlation between MPV and disease-free survival rate (hazard ratio 1.033, 95% CI 0.369-2.895). Our results showed that the MPV level was significantly higher in malignant tumors than in healthy subjects and was decreased after treatment. Further cumulative studies will be required before MPV levels can be applied for screening malignant tumors and predicting prognosis.

High Ki67/BCL2 index is associated with worse outcome in early stage breast cancer.

AIMS: Breast cancers are heterogeneous, making it essential to recognise several biomarkers for cancer outcome predictions. Ki67 proliferation index and B cell lymphoma 2 (BCL2) proteins are widely used as prognostic indicators in many types of malignancies. While Ki67 is a marker of normal or tumour cell proliferation, BCL2 plays a central role in antiproliferative activities. A combination of these two biomarkers with contrary purposes can provide enhanced prognostic accuracy than an analysis using a single biomarker. METHODS: We evaluated Ki67 and BCL2 expression with 203 cases of breast cancer. The relative expression of each biomarker named as Ki67/BCL2 index was divided into two groups (low vs high) with the use of area under receiver operating characteristic curves. RESULTS: There were significant correlations between Ki67/BCL2 index and clinicopathological findings such as age, tumour stage, size and necrosis, histological grade, extensive intraductal component, lymphatic and vascular invasion, oestrogen receptor, progesterone receptor, human epithelial growth factor receptor 2 and p53 expression (all p<0.05). In univariate and multivariate analyses, high Ki67/BCL2 index correlated with shorter disease-free survival and overall survival in patients with early stage invasive ductal carcinoma (all p<0.05). CONCLUSIONS: The Ki67/BCL2 index should be considered as a prognostic predictor in patients with early stage invasive ductal carcinoma.

Using Forceps Biopsy after Small Submucosal Dissection in the Diagnosis of Gastric Subepithelial Tumors.

The current tissue sampling techniques for subepithelial tumors (SETs) of the gastrointestinal (GI) tract have limited diagnostic efficacy. We evaluated the diagnostic yield and safety of forceps biopsies after small endoscopic submucosal dissection (SESD biopsies) in the diagnosis of gastric SETs. A total of 42 patients with gastric SETs > 10 mm were prospectively enrolled between May 2013 and October 2014. A dual knife was used to incise the mucosa and submucosa and forceps biopsies were then introduced deep into the lesion. To compare SESD biopsies with EUS-FNA, we used the retrospective data of 30 EUS-FNA cases. The diagnostic yield of SESD biopsies was comparable to that of EUS-FNA (35/42, 83.3% vs. 24/30, 80.0%, P = 0.717). The mean procedure time of SESD biopsies was shorter than that of EUS-FNA (10 vs. 37 minutes, P < 0.001). There were no procedure-related adverse events in the both group. The pathological diagnoses in SESD biopsies group included 15 leiomyomas, 7 GISTs, 10 heterotopic pancreases, 2 lipomas, and one other lesion. SESD biopsies are an easy, effective and safe technique for the diagnosis of gastric SETs and its diagnostic yield is comparable to that of EUS-FNA. This technique may be a reliable alternative to conventional EUS-FNA (Clinical trial registration No. KCT0000730).

Focal adhesion kinase and Src expression in premalignant and malignant skin lesions.

Focal adhesion kinase (FAK) and Src are non-receptor tyrosine kinases. FAK and Src play a critical role in inducing malignant transformation in tumor cells. We performed immunohistochemical staining for total and phosphorylated forms of FAK and Src, to evaluate the role of FAK and Src in the development of premalignant and malignant skin lesions. A total of 59 facial skin samples (30 actinic keratoses, 10 Bowen's diseases, 13 squamous cell carcinomas and six perilesional skins) were immunohistochemically stained for Ki-67, total (t) and phosphorylated (p) form of FAK and Src. Cells positive for t-Src, p-Src-y530, t-FAK and pFAK-s722 were detected in premalignant intra-epithelial lesions (PELs) and squamous cell carcinomas (SCCs), but not in the perilesional skin. There was a tendency towards high correlation between Ki-67 and t-FAK or pFAK-s722, suggestive of the active role of FAK in cell proliferation. However, our findings of higher t-Src and p-Src-y530 positive cells in PELs, as compared to SCCs (with higher Ki-67 level), are suggestive of the other role of Src in tumor formation and progression, which requires further investigation.

Pathological Predictors for Defining a Therapeutic Strategy for Early Colon Cancer after Endoscopic Resection: Multicenter Retrospective Analysis from Surgically Resected Specimens.

BACKGROUND/AIMS: For the possibility of regional lymph node metastasis (LNM), early colon cancer (ECC) is a boundary lesion between endoscopic resection and surgery. The aim of study is to clarify risk factors for LNM and to determine therapeutic strategy after endoscopic resection in patients with ECC. METHODOLOGY: The histopathology of patients with ECC underwent surgery with LN dissection in 8 university hospitals were reviewed by experienced pathologist blinded to LN status. RESULTS: In total, 370 patients (107 with mucosal cancer, 263 with submucosal invasive colorectal carcinoma [SICC]) were enrolled. Excluding mucosal cancer, the LNM rate was 11.8% (31/263, including 15.4% [8/52] with pedunculated SICC [P-SICC] and 10.9% [23/211] with non-pedunculated SICC [NP-SICC]). Multivariate analysis showed that tumor sprouting (P < 0.001; odds ratio [OR], 8.83; 95% confidence interval [CI], 3.04-25.69), submucosal invasion depth (SM depth) > 2000 µm (P = 0.024; OR, 3.68; 95% CI, 1.19-11.37), and lymphatic invasion (P = 0.022; OR, 3.48; 95% CI, 1.19-10.13) were related to LNM. All LNMs with SM depth < 2000 µm showed tumor sprouting without lymphatic invasion. CONCLUSIONS: Significant risk factors for predicting LNM in patients with SICC were tumor sprouting, SM depth > 2000 µm, and lymphatic invasion.

Diagnostic and prognostic relevance of MMP-11 expression in the stromal fibroblast-like cells adjacent to invasive ductal carcinoma of the breast.

BACKGROUND: Matrix metalloproteinase 11 (MMP-11) is a matrix degrading enzyme known to be involved in the remodeling of extracellular matrix proteins. This enzyme recently has been reported to play a key role in tumor progression and results in poor clinical outcomes for several different types of tumors. METHODS: A total of 192 patients diagnosed with invasive ductal carcinoma between 2000 and 2005 were included in this study. MMP-11 expression in tumors and stromal fibroblast-like cells was analyzed by immunohistochemical staining on a tissue microarray. Subsequently, evaluation of the associations between MMP-11 expression and clinicopathological characteristics was performed. RESULTS: MMP-11 expression of stromal fibroblast-like cells was correlated with prognostic factors, including tumor size, metastasis, histological grade, central tumor fibrosis, p53 expression, and luminal A subtype and was linked to therapeutic markers, such as ER and HER2 (all p < 0.05). There was a significant relationship between worse overall survival and MMP-11 expression in both tumors and stromal fibroblast-like cells (all p < 0.05). In multivariate analysis, MMP-11 expression of stromal fibroblast-like cells was still significantly associated with poor prognosis (p = 0.043). CONCLUSIONS: MMP-11 expression was significantly related to clinicopathological parameters, which may be essential to the prediction of disease outcome in patients with invasive ductal carcinoma of the breast.

Complete biopsy resection of diminutive polyps.

BACKGROUND AND STUDY AIMS: Cold biopsy forceps polypectomy (CBP) is commonly used for the removal of diminutive polyps; however, evidence for the efficacy of CBP is lacking. The aim of this study was to evaluate the adequacy of resection of diminutive polyps and to identify predictors for complete resection using CBP. PATIENTS AND METHODS: This was a prospective study from a tertiary referral hospital in Korea. A total of 196 patients were screened, and 65 patients with diminutive polyps were enrolled. CBP was used to resect diminutive polyps until no polyp was visible by chromoendoscopy using indigo carmine spray. Each polyp base was then resected using endoscopic mucosal resection (EMR) with a 1-3-mm free margin. CBP and EMR specimens were sent to the histopathology department for the evaluation of the completeness of the resection. Cross sections of the EMR specimens made at 1-mm intervals were examined by a pathologist. RESULTS: A total of 86 diminutive polyps were available for assessment. Overall, 90.7% (78/86) of the diminutive polyps were completely resected using CBP (95%CI 84.6-96.8%). The complete resection rate for all diminutive adenomas was 92.3 % (60/65; 95%CI 85.8-98.8%) and for 1-3-mm adenomas 100% (95%CI 81.5-100%). Polyp size, histology, and location, and number of biopsies were not different between the complete and incomplete resection groups. CONCLUSIONS: In this small study approximately 90 % of all diminutive polyps and 100% of 1-3-mm adenomatous polyps were completely resected using CBP and chromoendoscopy. CBP appears to be adequate for the resection of the majority of diminutive polyps, especially small sized adenomas (≤ 3 mm) if no residual tissue is visible by chromoendoscopy.

The prognostic relevance of psammoma bodies and ultrasonographic intratumoral calcifications in papillary thyroid carcinoma.

BACKGROUND: Although psammoma bodies (PB) are found in up to 50 % of papillary thyroid carcinomas (PTC), their clinicopathological significance remains uncertain. The aim of the present study was to determine the clinicopathological significance of PB and the correlation between PB and ultrasonographic intratumoral calcification in PTC. METHODS: The clinicopathological parameters, ultrasonographic calcifications, and the presence of PB were evaluated in 258 surgically resected conventional PTC. RESULTS: Psammoma bodies were found in 141 of 258 PTC (54.7 %). The presence of PB was significantly correlated with tumor multifocality, extrathyroidal extension, and lymph node metastasis (P = 0.009, P = 0.004, and P < 0.001, respectively), but not with the BRAF(V600E) mutation. Higher incidences of both intratumoral and extratumoral PB were found in overt PTC (>1 cm) than in papillary microcarcinomas (≤1 cm) (P < 0.001 and P = 0.015, respectively). Extratumoral PB were only identified in 48.9 % of 141 PTC with PB, and PTC with extratumoral PB showed higher incidences of tumor multifocality, extrathyroidal extension, and nodal metastasis compared to PTC with intratumoral PB (P = 0.014, P = 0.005 and P = 0.001, respectively). Ultrasonographic intratumoral calcification corresponded to clusters of intratumoral PB (P < 0.001) and was associated with nodal metastasis (P = 0.026). CONCLUSIONS: The findings of the present study suggest that the presence of PB may be a useful prognostic indicator of aggressive PTC behaviors. In addition, confirmation of ultrasonographic intratumoral calcification would be a useful decision-making criterion when determining the need for preoperative or intraoperative surveillance of nodal metastasis.

Chronic administration of ezetimibe increases active glucagon-like peptide-1 and improves glycemic control and pancreatic beta cell mass in a rat model of type 2 diabetes.

Ezetimibe is a cholesterol-lowering agent targeting Niemann-Pick C1-like 1, an intestinal cholesterol transporter. Inhibition of intestinal cholesterol absorption with ezetimibe may ameliorate several metabolic disorders including hepatic steatosis and insulin resistance. In this study, we investigated whether chronic ezetimibe treatment improves glycemic control and pancreatic beta cell mass, and alters levels of glucagon-like peptide-1 (GLP-1), an incretin hormone involved in glucose homeostasis. Male LETO and OLETF rats were treated with vehicle or ezetimibe (10 mg kg(-1)day(-1)) for 20 weeks via stomach gavage. OLETF rats were diabetic with hyperglycemia and significant decreases in pancreatic size and beta cell mass compared with LETO lean controls. Chronic treatment of OLETF rats with ezetimibe improved glycemic control during oral glucose tolerance test compared with OLETF controls. Moreover, ezetimibe treatment rescued the reduced pancreatic size and beta cell mass in OLETF rats. Interestingly, ezetimibe significantly decreased serum dipeptidyl peptidase-4 activity and increased serum active GLP-1 in OLETF rats without altering serum total GLP-1. These findings demonstrated that chronic administration of ezetimibe improves glycemic control and pancreatic beta cell mass, and increases serum active GLP-1 levels, suggesting possible involvement of GLP-1 in the ezetimibe-mediated beneficial effects on glycemic control.

Tumor-to-tumor metastasis: Hepatocellular carcinoma metastatic to parathyroid adenoma.

Tumor-to-tumor metastasis is a rare, but well-recognized phenomenon. Here, we report a unique case of hepatocellular carcinoma (HCC) metastatic to parathyroid adenoma. A 53-year-old-man with a history of HCC presented with hypercalcemia. It was found that he also had hyperparathyroidism with a hypoechoic mass in the lower portion of the right thyroid gland area. The patient underwent parathyroidectomy, and a mass measuring 1.5 × 1.0 cm was detected. Microscopic and immunohistochemical examination disclosed parathyroid adenoma with a focus of metastatic HCC. For the patient, it was the only distant metastasis revealed until the last follow-up. To the best of our knowledge, this is the first reported case of tumor-to-tumor metastasis in which HCC is the donor.

The effect of intra-articular autogenous bone marrow injection on healing of an acute posterior cruciate ligament injury in rabbits.

PURPOSE: The purpose was to identify the effect of intra-articular autogenous bone marrow injection on the healing of an acute posterior cruciate ligament (PCL) rupture in a rabbit model. The effect of autogenous bone marrow on the healing process was assessed serially by gross inspection, histologic examination, and immunohistochemical study of growth factors. METHODS: In both knee joints, the PCL was completely transected surgically near the femoral attachment site in 24 rabbits. Autogenous bone marrow was obtained from both tibias and delivered only to the right knee joint by direct intra-articular injection. Gross inspection, histologic examination, and immunohistochemical study of growth factors were performed at 8, 12, and 16 weeks after severing of the posterior cruciate ligament (PCL) among 8 randomly chosen specimens. The degree of healing in both marrow-stimulated and untreated control ligaments was evaluated by gross inspection using an ordinal scale consisting of 5 grades. The degree of fibroblast and vessel proliferation and alignment of collagen fibers were evaluated by histologic examination. The degree of expression of transforming growth factor ß1, epidermal growth factor receptor, and vascular endothelial growth factor was evaluated by immunohistochemical study. Statistical analysis was performed with the Mann-Whitney U test. RESULTS: In the group with marrow-stimulated ligaments, the degree of healing was higher at 8 and 12 weeks by gross examination, whereas there was no significant difference at 16 weeks between the 2 groups. According to histologic examination, the healing process was faster in the bone marrow injection group than in the control group at 8 and 12 weeks because the degree of fibroblast and vessel proliferation significantly declined and collagen fibers were arranged more regularly compared with the control group. Similar to the results of histologic examination, the results of immunohistochemical studies showed that the healing process was faster in the bone marrow injection group. However, the recovery of the PCL was completed at 16 weeks after PCL resection in both the bone marrow injection group and the control group. CONCLUSIONS: Intra-articular autogenous bone marrow injection appeared to promote the initiation of healing response in acutely injured PCLs in rabbits. CLINICAL RELEVANCE: Intra-articular autogenous bone marrow injection can be a viable option for treating acutely injured PCLs.

Proto-oncogene Pokemon in thyroid cancer: a potential promoter of tumorigenesis in papillary thyroid carcinoma.

BACKGROUND: Pokemon is an oncogenic transcription regulator that plays a critical role in cellular differentiation. Although it has been found to be overexpressed in several types of cancer involving different organs, its role in thyroid gland has yet to be reported. The objective of this study was to evaluate the expression of Pokemon in papillary thyroid carcinoma (PTC) based on clinicopathological parameters. METHODS: Tissue microarray samples derived from patients with PTC or benign thyroid disease were used to evaluate Pokemon expression based on immunohistochemical analysis. Correlations of its expression with various clinicopathological parameters were then analyzed. RESULTS: Pokemon expression was observed in 22.0% of thyroid follicular cells from the normal group, 44.0% from the group with benign thyroid diseases, and 92.1% from the group with PTC (p < .001). The intensity of Pokemon expression was markedly higher in the PTC group. Pokemon expression level and PTC tumor size showed an inverse correlation. T1a tumors showed strong expression levels of Pokemon. However, larger tumors showed weak expression (p = .006). CONCLUSIONS: Pokemon expression is associated with tumorigenesis of PTC, with expression showing an inverse correlation with PTC tumor size. This might be related to the negative regulation of aerobic glycolysis by Pokemon.

Clinicopathological characteristics and outcomes of gastrointestinal stromal tumors with high progranulin expression.

BACKGROUND & AIMS: Progranulin (PGRN) is known to promote tumorigenesis and proliferation of several types of cancer cells. However, little is known about the clinicopathological features of patients with gastrointestinal stromal tumors (GISTs) with regard to PGRN expression. METHODS: A retrospective analysis was performed on patients with GISTs who underwent curative surgical resection between 2007 and 2017. PGRN expression was evaluated by immunohistochemical (IHC) analysis and semi-quantitatively categorized (no expression, 0; weak, 1+; moderate, 2+; strong, 3+). Tumors with a staining intensity of 2+ or 3+ were considered high PGRN expression. RESULTS: Fifty-four patients were analyzed; 31 patients (57%) were male. The median age at surgery was 60 years (range, 33-79), and the most common primary site was the stomach (67%). Thirty-five patients (65%) had spindle histology; 42 patients (78%) were separated as a high-risk group according to the modified National Institutes of Health (NIH) classification. High PGRN-expressing tumors were observed in 27 patients (50%), had more epithelioid/mixed histology (68% vs. 32%; p = 0.046), and KIT exon 11 mutations (76% vs. 24%; p = 0.037). Patients with high PGRN-expressing tumors had a worse recurrence-free survival (RFS) (36% of 5-year RFS) compared to those with low PGRN-expressing tumors (96%; p<0.001). Multivariate analysis showed that high PGRN expression and old age (>60 years) were independent prognostic factors for poor RFS. CONCLUSIONS: High PGRN-expressing GISTs showed more epithelioid/mixed histology and KIT exon 11 mutations. PGRN overexpression was significantly associated with poor RFS in patients with GISTs who underwent curative resection.

Standardization of the pathologic diagnosis of appendiceal mucinous neoplasms.

Although the understanding of appendiceal mucinous neoplasms (AMNs) and their relationship with disseminated peritoneal mucinous disease have advanced, the diagnosis, classification, and treatment of AMNs are still confusing for pathologists and clinicians. The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists (GPSG-KSP) proposed a multicenter study and held a workshop for the "Standardization of the Pathologic Diagnosis of the Appendiceal Mucinous Neoplasm" to overcome the controversy and potential conflicts. The present article is focused on the diagnostic criteria, terminologies, tumor grading, pathologic staging, biologic behavior, treatment, and prognosis of AMNs and disseminated peritoneal mucinous disease. In addition, GPSG-KSP proposes a checklist of standard data elements of appendiceal epithelial neoplasms to standardize pathologic diagnosis. We hope the present article will provide pathologists with updated knowledge on how to handle and diagnose AMNs and disseminated peritoneal mucinous disease.

Overexpression of p53 is correlated with poor outcome in premenopausal women with breast cancer treated with tamoxifen after chemotherapy.

The aim of this study was to evaluate the difference in outcomes based on p53 overexpression of patients with breast cancer who received adjuvant therapy following local treatment for invasive ductal carcinoma, not otherwise specified. We analyzed data from 4,683 patients with cancer enrolled in two institutions between 1997 and 2006. We analyzed the correlation between p53 overexpression and relapse, response to adjuvant therapy, breast cancer-specific survival (BCSS), and relapse-free survival (RFS) in patients with primary breast cancer. Overexpression of p53 was noted in 1,091 patients (23.3%). A significant correlation existed between p53 overexpression and poor prognostic factors, an increased frequency of regional recurrence, visceral metastasis, and worse BCSS and RFS. Based upon subgroup analyses, combined age (<35, 35-50, and >50 years) and adjuvant therapy (hormone therapy only, chemotherapy only, and hormone therapy following chemotherapy), the greatest reduction of survival based on p53 overexpression was noted in patients 35-50 years of age who received hormone therapy following chemotherapy (P < 0.05). Multivariate analysis showed that p53 overexpression is an independent prognostic factor in patients treated with hormone therapy and chemotherapy (relative risk for BCSS, 2.003; 95% CI, 1.105-3.631; P = 0.022). The p53-overexpressing patients with breast cancer between 35 and 50 years of age who received tamoxifen following chemotherapy had the greatest adverse effect on outcome. Overexpression of p53 is significantly associated with tamoxifen resistance in premenopausal women with breast cancer.