Il-6 and MSH3 in colorectal carcinoma: Expression, relationship, and prognostic significance in 171 colorectal carcinoma cases.

AIMS: Colorectal cancer (CRC), the most common type of gastrointestinal cancer, mostly develops as a result of environmental factors. Inflammation is a relatively uncommon but crucial contributor to its etiology, and inflammation is also thought to pose a risk in patients without a clinical diagnosis of inflammatory bowel disease. In cell lines, the proinflammatory cytokine interleukin-6 (IL-6) causes a cytosolic shift in the mismatch repair protein MSH3, accompanied by functional loss. This study aimed to evaluate IL-6 and MSH3 expression in 171 sporadic CRC samples by immunohistochemistry (IHC). High levels of IL-6 are hypothesized to cause MSH3 expression loss. We also explored the clinical/pathological aspects of IHC-detected MSH3 loss and the relationship between MSH3 expression and tumor-infiltrating lymphocytes (TILs). MATERIALS AND METHODS: IL-6 and MSH3 IHC and H and E slides were evaluated by two pathologists. Clinical data were obtained from the institution's database. RESULTS: A relationship between MSH3 loss and IL-6 expression was not proven (P = 0.963). MSH3 staining was significantly reduced in the patient group with high TILs (P = 0.035). We observed 104 CRC cases (60.8%) with IL-6 expression and 85 cases (49.7%) with reduced MSH3 expression. CONCLUSION: This study did not demonstrate an association between IL-6 and MSH3 expression. As MSH3 is a relatively little-known protein, further large-scale studies are needed. The use of IHC to identify patients who may benefit from anti-IL-6 therapies in CRC in the future may be critical.

The effect of Pilates-based exercise applied with hybrid telerehabilitation method in children with adolescent idiopathic scoliosis: A randomized clinical trial.

This study aimed to investigate the effect of Pilates-based exercise training applied with hybrid telerehabilitation on Cobb angle, respiratory function, respiratory muscle strength, and functional capacity in patients with adolescent idiopathic scoliosis (AIS). This is an evaluator-blinded, randomized, controlled trial. For the study, 32 patients were randomly allocated into two groups: a hybrid telerehabilitation group (training group), provided with modified Pilates-based exercises with synchronous sessions; and a home-based group (control group), doing the same exercises in their home. The Pilates-based exercise program consists of stretching and strengthening exercises combined with postural corrections and breathing exercises modified according to the curve type and localization of the patients, done every day of the week for 12 weeks. Analyses were made based on the comparison between the angle of trunk rotation, Cobb angle, spirometry, maximal inspiratory (MIP) and expiratory pressures (MEP), and incremental shuttle walk tests done at the beginning and end of the study. The training group showed statistically significant improvements in Cobb angle, PEF%, MIP, and MEP values compared with the control group (p < 0.05). CONCLUSION:  Pilates-based exercises applied with the hybrid telerehabilitation method can improve Cobb angle and respiratory muscle strength in patients with AIS. The hybrid telerehabilitation method can be used as an alternative to home-based programs, especially in locations and times where there may be limited access to supervised training. Also, the nature of the disease that requires long-term follow-up is another factor where hybrid telerehabilitation may be an advantage. TRIAL REGISTRATION:  ClinicalTrials.gov ID: NCT05761236. WHAT IS KNOWN: • Exercise training is one of the main approaches to treating scoliosis. WHAT IS NEW: • Application of exercises via telerehabilitation method may contribute more to the improvement of scoliosis-related parameters than home-based programs. • Telerehabilitation may be a preferable alternative exercise method in scoliosis, considering the advantages of accessibility and long-term follow-up.

Tumor-Infiltrating Lymphocytes (TIL), Tertiary Lymphoid Structures (TLS), and Expression of PD-1, TIM-3, LAG-3 on TIL in Invasive and In Situ Ductal Breast Carcinomas and Their Relationship with Prognostic Factors.

INTRODUCTION: Immunotherapy has been determined as an important choice in breast carcinomas, especially in tumors with markedly inflammatory response. About this promising subject, tumor-infiltrating lymphocytes (TIL) and the expression of immune control point receptors on TIL have gained importance. MATERIALS AND METHODS: In this study, stromal TIL and tertiary lymphoid structures (TLS) were determined in tumor tissues of 312 invasive and 68 in situ breast cancer patients. Expression rates of PD-1, LAG-3, and TIM-3 on intratumoral and stromal TIL were immunohistochemically evaluated. RESULTS: In invasive breast carcinomas, stromal TIL was found to be significantly associated with lymph node metastasis, HR and HER2 expression, and basal-like phenotype, as the presence of TLS with neoadjuvant therapy, recurrence, death, and expression of HR and HER2. PD-1, LAG-3, and TIM-3 expressions were found to be associated with HR and HER2 status, stromal TIL rates, and TLS. In multivariate analysis, high stromal TIL and PD-1 expression in intratumoral TIL were found to be independent prognostic factors in terms of overall survival and disease-free survival. CONCLUSION: Evaluation of TIL and immune control point receptor expressions in breast cancer is particularly important in terms of planning the therapeutic approaches based on immunotherapy protocols.

Could there be an association between Hashimoto's thyroiditis and demodex infestation?

BACKGROUND: Human demodex mites are parasites that live in the pilosebaceous unit and can result in the disease demodicosis. While demodicosis may occur as a primary skin disease; immunosuppression, and topical or systemic immunosuppressive treatments can cause secondary demodicosis. It is known that thyroid hormones may cause skin changes, such as xerosis, and thereby may also modulate immune responses in the skin. OBJECTIVES: The aim of this study is to investigate whether or not that the changes occurring in the skin of patients with Hashimoto's Thyroiditis (HT) predispose to demodex infestation. METHODS: Seventy-eight patients being followed for a diagnosis of HT at Kocaeli University Endocrinology Outpatient Clinic, between January 2019 and March 2020, constituted the patient group. The control group consisted of 41 patients who did not have any chronic systemic or dermatological disease and were shown to have no thyroid disease by laboratory tests. Demodex intensity in the malar regions of the patient and control groups was determined using the standardized skin surface biopsy (SSSB) method and compared with each other. RESULTS: HT patients were significantly more likely to have increased demodex density and suggestive SSSB results than the controls (p < 0.001, p = 0.012, respectively). A significant correlation was found between demodex intensity and the findings of xerosis (p = 0.010, p = 0.011) and spiny follicular papules (p = 0.008, p = 0.008) in the patient or control groups, respectively. However, a significant correlation was identified between the demodex density and the symptoms of burning-stinging (p = 0.028), and feelings of dryness (p = 0.018) roughness (p = 0.028) only in the control group. CONCLUSION: Xerotic skin and/or impaired immune responses as a result of autoimmune changes in patients with HT may lead to secondary demodicosis.

Comparison of the efficiency of transgelin, smooth muscle myosin, and CD31 antibodies for the assessment of vascular tumor invasion and free tumor deposits in gastric, pancreatic, and colorectal adenocarcinomas.

BACKGROUND: This study aimed to compare CD31, smooth muscle myosin (SMM), and transgelin antibodies for their efficiency in detecting venous invasion (VI) and the nature of free tumor deposits (TDs) in gastric, pancreatic, and colorectal adenocarcinomas. MATERIALS AND METHODS: Eleven Whipple, 5 gastrectomy, and 3 colectomy specimens and 1 low anterior resection specimen were reviewed and examined, revealing 254 probable foci. Foci were reviewed and divided into 3 types: Type A, the "orphan artery" pattern; Type F, free TDs in the periorgan adipose and connective tissue without an unaccompanied artery; and Type X, a focus that could be detected only with the immunohistochemical procedures mentioned. RESULTS: No foci were positive for CD31. Transgelin staining was more sensitive than SMM staining in all focus types, Type A only and Type F only (P < 0.001, P = 0.001, and P = 0.10, respectively). In free TDs (Type F), 35.7% of the samples were negative for all four stains, and 64.2% of the samples were positive for SMM and transgelin. We did not make the distinction between a metastatic lymph node and VI in positive foci. CONCLUSION: We conclude that hematoxylin and eosin (H and E) staining is inadequate and that smooth muscle markers, such as transgelin and/or SMM, are more effective than endothelial markers, such as CD31, in revealing VI and lymph node/large extramural invasion.

Compared With Elastin Stains, h-Caldesmon and Desmin Offer Superior Detection of Vessel Invasion in Gastric, Pancreatic, and Colorectal Adenocarcinomas.

BACKGROUND: The presence of vessel invasion is considered indicative of a poor prognosis in many malignant tumors. We aimed to compare the sensitivity of elastin stains (van Gieson's and orcein methods) with 2 smooth muscle markers (h-caldesmon and desmin) in gastric, pancreatic, and colorectal adenocarcinoma specimens. MATERIALS AND METHODS: We used 27 (29.3%) gastric, 35 (38.0%) pancreatic, and 30 (32.6%) colorectal resection specimens. We applied a provisional classification of vessel invasion patterns: type A, a focus with a nearby artery unaccompanied by a vein; type T, a focus at the invasive front without an unaccompanied artery; and type X, foci that only appeared by any of the 4 stains used. RESULTS: There were 369 foci. The smooth muscle markers were more sensitive than the elastin stains, and h-caldesmon more sensitive than desmin, in all types. Among the 139 type A foci, 33 (23.7%) were positive by desmin and h-caldesmon, whereas the elastin stains were not ( P = .001). h-Caldesmon was the only positive marker in 11 (7.9%; P = .011). Among the 78 type T foci, 21 (26.9%) were positive by desmin and h-caldesmon, when both elastin stains were negative ( P = .000). In 16 (20.5%) foci, h-caldesmon was the only positive marker ( P = .002). Among 152 type X foci, 91 (59.9%) were positive by all markers, 26 (17.1%) by both desmin and h-caldesmon, and 9 (5.9%) by only the 2 elastin stains ( P = .001). CONCLUSION: We recommend these stains for suspect foci in gastric, pancreatic, and colorectal adenocarcinoma specimens. They might highlight both predictable and unpredictable foci.

Thymosin beta-4 overexpression correlates with high-risk groups in gastric gastrointestinal stromal tumors: A retrospective analysis by immunohistochemistry.

BACKGROUND: Thymosin beta-4 (Tß4) is a protein that is linked to a number of important biological actions and recently tumor progression and poor prognosis of some tumors. The aim of this study was to evaluate Tß4 expression in gastric GISTs and correlate with some clinicopathological characteristics related with prognosis and clinical outcome in order to add further data to the current literature. METHODS: Tß4 antibody was applied to the 4µm-thick paraffin sections of 57 gastric GISTs by immunohistochemistry. RESULTS: Tß4 expression was found to be directly corrrelated with higher risk groups, tumor size, mitotic count, cellularity, and necrosis while it was inversely correlated with overall survival (OS) by univariate analysis (p=0.000, p=0.001, p=0.000, p=0.025, p=0.023, and p=0.042, respectively). The direct association between Tß4 expression and risk groups were also supported by multivariate analysis (p=0.000, ß=0.497, t=4.374). CONCLUSION: Overexpression of Tß4 was found to be related with predictive characteristics for tumor progression and adverse prognosis. Thus, we suggest that overexpression of Tß4 might play a role in the progression of gastric GISTs and might be used as a potential prognostic tool as well as a target for novel therapies.

The prognostic significance of ING4 expression on gastric gastrointestinal stromal tumors by immunohistochemistry.

OBJECTIVE: Inhibitor of growth 4 (ING4) is a novel tumor suppressor gene that is reported to be down-regulated in various tumors including gastrointestinal stromal tumors (GISTs) originated from different locations, recently. Herein, we aimed to evaluate ING4 expression and its prognostic significance on gastric GISTs in order to add further data to the current literature. MATERIAL AND METHODS: ING4 was evaluated in samples of gastric GISTs from 62 patients, by immunohistochemistry. The association between ING4 expression and clinicopathological features related with prognosis and overall survival (OS) were analyzed statistically. RESULTS: There was statistically significant inverse correlation between ING4 expression and risk groups according to both NIH and AFIP, Ki67 index, tumor diameter, and mitotic count by univarite analysis (p=0.000, p=0.000, p=0.08, p=0.01, and p=0.028, respectively). The negative association between ING4 expression and risk groups according to both NIH (p=0.002, ß=-0.263, t=-3.166) and AFIP (p=0.016, ß=-0.244, t=-2.492) was supported by multivariate analysis. There was statistically significant direct correlation between low levels of ING4 expression and shorter OS by univariate (p=0.000) and multivariate analysis (p=0.000, ß=0.769, t=9.798), as well as Kaplan-Meier method (p=0.035). CONCLUSIONS: The low ING4 expression level was found to be related with unfavorable prognosis. Thus, we suggest that loss of ING4 expression might play a role in the progression of GISTs and might be used as a potential prognostic tool. Additionally, this is the first study that has evaluated the association of ING4 expression on gastric GISTs, to the best of our knowledge. Therefore, we claim that more comprehensive future studies including higher number of patients and longer follow-up might clarify the potential role of ING4 on pathogenesis and prognosis of GISTs. KEY WORDS: Clinicopathological features, Gastrointestinal stromal tumor, ING4, Immunohistochemistry.

Clinicopathologic and prognostic significance of immunohistochemical expression of HIF-1α, CXCR4 and CA9 in colorectal carcinoma.

OBJECTIVE: To investigate the immunohistochemical expressions of HIF-1α, CA9 and CXCR4 in resected human CRC specimens in relation to clinicopathologic and prognostic variables. METHODS: A total of 186 patients (mean(SD) age: 56.7(12.6) years, 54.0% were males) with colorectal adenocarcinoma were included in this retrospective study. Resection specimens of the primary tumor were reviewed to confirm the diagnoses and the stage of the disease. Data on age, gender, tumor characteristics (localization, size, macroscopic growth pattern, histologic type, grade, angiolymphatic invasion, TNM stage), applied treatments and clinical outcome (overall survival, local recurrence and distant metastasis) were obtained from the hospital records. Immunohistochemical analysis of tissue specimens was performed to determine HIF-1α, CA9 and CXCR4 expressions. RESULTS: Overall, 94.0% of cases showed HIF-1α immunoreactivity, 89% showed CXCR4 immunoreactivity, and 15.6% showed CA9 immunoreactivity, while weak expression of immunohistochemical markers was noted in 51.1%, 93.0% and 50.5% of cases, respectively. HIF-1α expression was higher among males than in females (median (min-max) final score of 6 (0-9) vs. 3 (0-9), p=0.013). CA9 expressed at higher levels in ulcerovegetative and depressed tumors than in polypoid ones [0(0-9) vs. 0(0-6), p=0.039]. CXCR4 expression was significantly higher in tumors <5cm than ≥5cm [6(0-9) vs. 3(0-9), p=0.028] and in grade 1-2 than grade 3 tumors [4(0-9) vs. 3(0-9), p=0.030]. No significant difference was noted in survival with respect to strength of HIF-1α, CA9 and CXCR4 immunoreactivity. CONCLUSION: In conclusion, our findings revealed weak-to-moderate HIF-1α and CXCR4 immunoreactivity in majority of resection samples, and weak CA9 immunoreactivity in majority of CA9 positive cases. Other than gender (HIF-1α), macroscopic growth pattern (CA9) and tumor size and histologic grade (for CXCR4), none of the clinicopathologic and prognostic factors investigated were associated with expression of immunohistochemical markers and level of immunoreactivity had no impact on survival.

The Diagnostic and Prognostic Utility of DOG1 Expression on Gastrointestinal Stromal Tumors.

OBJECTIVE: We aimed to review our archives in order to evaluate both the diagnostic and prognostic significance of DOG1 on gastrointestinal stromal tumors (GISTs), and add further insight about those issues to the current literature including some conflicting results. MATERIAL AND METHOD: DOG1 was evaluated in 100 cases of GISTs, immunohistochemically. Immunostaining index was counted for each antibody by using both the intensity and extent of staining. The association between immunostaining index of DOG1 and CD117, CD34, SMA desmin, S-100, and Ki-67 index and clinicopathological features were analyzed. RESULTS: Ninety cases were positive for DOG1, and 89 were positive for CD117. All CD117-negative tumors were positive for DOG1. High-risk group was directly correlated with tumor diameter, cellularity, necrosis, nuclear pleomorphism, mitotic count and Ki-67 index, by univariate analysis. The association between high-risk group and tumor diameter, mitotic count, and Ki-67 index was proved by multivariate analysis. Immunostaining index of DOG1, Ki-67 index, mitotic count, ulceration and hemorrhage were inversely correlated with overall survival by univariate analysis. The adverse impact of DOG1 ISI and mitotic count on overall survival were supported by multivariate analysis. CONCLUSION: DOG1 positivity was detected in most of GISTs and all in CD117-negative cases as a result underlining its diagnostic utility. Additionally, DOG1 overexpression was related with adverse prognosis. Thus, we suggest that immunostaining index of DOG1 should routinely be used while diagnosing GIST, and DOG1 might be considered as a potential prognostic tool and a target for novel therapies.

Proliferation markers RacGAP1 and Ki-67 in gastrointestinal stromal tumors by immunohistochemistry with respect to clinicopathological features and different risk stratification systems.

RacGAP1 is a protein associated with cell proliferation, cell growth regulation, cell transformation and metastasis. The present study was designed to evaluate RacGAP1 expression in gastrointestinal stromal tumors (GISTs) for the first time in the literature and to determine its association with some predictive clinicopathological features, Ki-67 proliferation index, and risk stratification systems of Armed Forces Institute of Pathology (AFIP) and modified National Institutes of Health (NIH). Paraffin-embedded tissues of 100 GISTs were investigated, retrospectively. High (≥10%) Ki-67 proliferation index, higher mitotic count, high cellularity, small intestinal location, and high-risk groups according to both AFIP and modified NIH criteria were found to be correlated with RacGAP1 positivity in the univariate analysis (all P values <0.05). The association between RacGAP1 expression and higher cellularity was supported by the multivariate analysis (P=0.023). High (≥10%) Ki-67 proliferation index was correlated with higher nuclear pleomorphism, necrosis, ulceration, small intestinal location, greater tumor size, higher mitotic count, and high risk group according to AFIP and NIH criteria in the univariate analysis (all P values <0.05). The correlation of Ki-67 proliferation index and mitotic count and high risk group according to AFIP criteria was confirmed by the multivariate analysis (all P values <0.05). In conclusion, higher RacGAP1 expression and Ki-67 index might be considered as effective complementation of risk stratification systems and unfavorable clinicopathological features in predicting poor outcome of GISTs. However, the utility of RacGAP1 expression in GISTs should be further validated in larger cohorts of patients with long-term follow-up data.

Relationship between indoleamine 2,3-dioxygenase activity and lymphatic invasion propensity of colorectal carcinoma.

AIM: To evaluate whether serum and tumor indoleamine 2,3-dioxygenase activities can predict lymphatic invasion (LI) or lymph node metastasis in colorectal carcinoma. METHODS: The study group consisted of 44 colorectal carcinoma patients. The patients were re-grouped according to the presence or absence of LI and lymph node metastasis. Forty-three cancer-free subjects without any metabolic disturbances were included into the control group. Serum neopterin was measured by enzyme linked immunosorbent assay. Urinary neopterin and biopterin, serum tryptophan (Trp) and kynurenine (Kyn) concentrations of all patients were determined by high performance liquid chromatography. Kyn/Trp was calculated and its correlation with serum neopterin was determined to estimate the serum indoleamine 2,3-dioxygenase activity. Tissue sections from the studied tumors were re-examined histopathologically and were stained by immunohistochemistry with indoleamine-2,3-dioxygenase antibodies. RESULTS: Neither serum nor urinary neopterin was significantly different between the patient and control groups (both P > 0.05). However, colorectal carcinoma patients showed a significant positive correlation between the serum neopterin levels and Kyn/Trp (r = 0.450, P < 0.01). Urinary biopterin was significantly higher in cancer cases (P < 0.05). Serum Kyn/Trp was significantly higher in colorectal carcinoma patients (P < 0.01). Lymphatic invasion was present in 23 of 44 patients, of which only 12 patients had lymph node metastasis. Eleven patients with LI had no lymph node metastasis. Indoleamine-2,3-dioxygenase intensity score was significantly higher in LI positive cancer group (44.56% ± 6.11%) than negative colorectal cancer patients (24.04% ± 6.90%), (P < 0.05). Indoleamine 2,3-dioxygenase expression correlated both with the presence of LI and lymph node metastasis (P < 0.01 and P < 0.05, respectively). A significant difference between the accuracy of diagnosis by using either total indoleamine-2,3-dioxygenase immunostaining score or of lymph node metastasis was found during the evaluation of cancer patients. CONCLUSION: Indoleamine-2,3-dioxygenase expression may predict the presence of unrecognized LI and lymph node metastasis and may be included in the histopathological evaluation of colorectal carcinoma cases.

Two gastrointestinal conditions with similar symptoms and endoscopic appearance: irritable bowel syndrome and microscopic colitis.

BACKGROUND/AIM: Irritable bowel syndrome (IBS) is a gastrointestinal condition characterized by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits in the absence of any organic cause. This trial investigated the presence of microscopic colitis (MC) and associated factors related to MC in patients diagnosed with IBS. MATERIALS AND METHODS: The study group (group I) consisted of 91 consecutive patients diagnosed with IBS based on the Rome III Criteria for whom colonoscopic examination was requested. The control group (group II) had 41 patients diagnosed with IBS considered as eligible for colonoscopic investigation due to specific conditions, and for whom colonoscopic examination was recommended for screening purposes due to a familial history of colon cancer. Clinical data, endoscopic findings, and the effects of the therapy were evaluated. RESULTS: In the diarrhea-predominant IBS group, nine patients (9.89%) were diagnosed with microscopic colitis, seven with lymphocytic colitis (7.69%), and two with collagenous colitis (CC) (2.19%). None of the patients in group II were found to have MC (P = 0.007). There were no diagnoses of MC in the constipation-predominant and mixed type IBS groups. CONCLUSION: Clinicians should keep MC in mind for patients presenting with diarrhea-predominant IBS symptoms.

Discordances in HER2 status between primary gastric cancer and corresponding metastatic sites.

OBJECTIVE: Determination of human epidermal growth factor receptor-2 status in advanced gastric cancer is important in clinical decision making. In the trastuzumab for GC trial, trastuzumab-based therapy demonstrated a significant overall survival benefit in patients with human epidermal growth factor receptor-2-positive advanced gastric cancer. Human epidermal growth factor receptor-2 discordance in gastric cancer primary and its metastases has been long debated. The aim of the study was to evaluate the rate of human epidermal growth factor receptor-2 discordance and its effect on treatment decisions in advanced gastric cancer. METHODS: A total of 74 patients with advanced gastric cancer were included in the study. Both immunohistochemical staining and dual-color silver in situ hybridization were performed in all patients to evaluate the human epidermal growth factor receptor-2 status of the primary lesion and paired metastasis. RESULTS: The assessment of human epidermal growth factor receptor-2 status with the immunohistochemical staining method and dual-color silver in situ hybridization revealed a discordance rate of 9.5 and 16.2%, respectively. However, this discordance was clinically meaningful in only one patient leading to a change in treatment decision. While this patient had a human epidermal growth factor receptor-2-negative status in primary tumor (immunohistochemical = 0, dual-color silver in situ hybridization = negative), the human epidermal growth factor receptor-2 status was positive for liver metastasis (immunohistochemical = 2+, dual-color silver in situ hybridization = positive). Trastuzumab was added to the chemotherapy regimen. CONCLUSIONS: In this study, we found a higher rate of human epidermal growth factor receptor-2 discordance between primary gastric tumor and metastatic lesions compared with the rates reported in previous studies. Detection of a human epidermal growth factor receptor-2-positive metastasis with a human epidermal growth factor receptor-2-negative primary tumor suggests that investigation of human epidermal growth factor receptor-2 is also required for the metastatic lesion and that trastuzumab could be administered in the case of a positive result.

A rare cause of protein losing enteropathy: collagenous sprue.

Collagenous sprue is a clinicopathological entity with an unknown etiology. Its clinical features include progressive malabsorption, diarrhea, weight loss, unresponsiveness to treatment, and high mortality rates. The age interval of collagenous sprue is quite broad and ranges between 2 and 85 years. As far as to our knowledge, the presented case is the first reported case in infancy.

Comparison of WHO 2000 and WHO 2010 classifications of gastroenteropancreatic neuroendocrine tumors.

BACKGROUND/AIMS: Grading and staging are important in gastroenteropancreatic neuroendocrine tumors for directing treatment. In this study, we evaluated the histopathological parameters of gastroenteropancreatic neuroendocrine tumors and statistically analyzed the correlations of these parameters between the World Health Organization (WHO) 2000 and 2010 classifications. MATERIALS AND METHODS: A total of 77 cases diagnosed as neuroendocrine tumors were included in the study. Cases were classified according to the WHO 2000 and WHO 2010 classification systems, and the differences and correlations between the two systems were discussed. RESULTS: Among the 50 cases that were diagnosed as well-differentiated neuroendocrine tumor according to WHO 2000, 45 were found to be Grade 1 and 5 were found to be Grade 2 according to the WHO 2010 classification. Among the 8 cases with well-differentiated neuroendocrine carcinoma according to WHO 2000; 5 and 3 were Grade 1 and Grade 2, respectively, according to the WHO 2010 classification. All of the 19 cases with poorly differentiated neuroendocrine carcinoma according to WHO 2000 were found to be Grade 3 according to the WHO 2010 classification. No differences were found between the classifications in the poorly differentiated group with a full correlation between the two classifications. CONCLUSION: Although WHO 2000 seems to be a better classification to predict prognosis, since it is based on various parameters, such as depth of invasion, angiolymphatic invasion, and presence of metastasis, it was concluded that there was no difference between the WHO 2000 and WHO 2010 classification, which is based on only the number of mitoses and Ki-67 proliferation index.

The role of interleukin-1 gene polymorphisms and Helicobacter pylori in gastroesophageal reflux disease.

BACKGROUND/AIMS: Our aim is to assess the relationship between interleukin 1ß (IL-1 ß), (-511,-31 alleles), interleukin 1RN (IL-RN), Helicobacter pylori (HP) status and gastroesophageal reflux disease (GERD) diagnosed by pH monitoring in the Turkish population. MATERIALS AND METHODS: A Total of 100 consecutive patients with GERD were enrolled in the study. Genotypes of IL-1ß (-511,-31), IL-1RN gene polymorphisms and HP status of the patients were analyzed. RESULTS: While thirty-two patients were diagnosed as esophagitis with varying severity the remaining patients had no esophagitis. Seventy six participants were positive for HP and the remaining patients were negative. The difference between erosive and non-erosive groups was statistically significant when we compared IL-1ß (-511) but no difference regarding IL-1ß (-31) and IL-1RN variations. We also analyzed T/T, C/T and C/C alleles and the difference was significant statistically in T/T allele between patients with and without erosive GERD 1 (3.1%) vs. 12 (17.9%), respectively with a p value<0.05. But C/C, C/T alleles of (-511), (-31) and IL-1RN polymorphisms were not statistically significant between the groups. CONCLUSION: IL-1ß genetic polymorphisms may take part in the pathophysiology of gastroesophageal reflux disease.

Assessment of COX-2 expression presence and severity by immunohistochemical method in patients with chronic active gastritis and intestinal metaplasia.

BACKGROUND/AIMS: The risk of gastric cancer is increased in patients with intestinal metaplasia. Cyclooxygenase-2 activity is crucial for gastric cancer cell survival and proliferation. We aimed to assess cyclooxygenase-2 expression in patients with intestinal metaplasia or chronic active gastritis and in patients with or without a family history of gastric cancer, i.e. a first-degree relative with gastric cancer. MATERIALS AND METHODS: One hundred and six patients with histologically proven intestinal metaplasia, chronic active gastritis or normal gastric mucosa were included. Immunohistochemical staining was performed using the immunoperoxidase method. RESULTS: Cyclooxygenase-2 expression was detected in 23.1% of normal gastric mucosa, 70.6% of chronic active gastritis, and 90.5% of intestinal metaplasia patients. Cyclooxygenase-2 expression was significantly higher in intestinal metaplasia than in chronic active gastritis (p=0.018). Cyclooxygenase-2 expression was significantly more severe in the intestinal metaplasia group when compared to the chronic active gastritis group (p=0.017). Severe cyclooxygenase-2 expression (>60% of cells) was more frequent in the intestinal metaplasia group. Cyclooxygenase-2 expression was higher in the Helicobacter pylori-positive group when compared to the Helicobacter pylori-negative group (80.3% vs 57.1%, respectively; p=0.012). Cyclooxygenase-2 expression did not significantly differ according to presence of a first-degree relative with gastric cancer. CONCLUSIONS: Patients with intestinal metaplasia demonstrated increased presence and severity of cyclooxygenase-2 expression. Our findings suggest that cyclooxygenase-2 plays an important role in the stepwise process that eventually leads to gastric cancer. There was no statistically significant difference between the patients with and without a first-degree relative with a history of gastric cancer in terms of cyclooxygenase-2 expression.

Serrated polyps of the colon: how reproducible is their classification?

For several years, the lack of consensus on definition, nomenclature, natural history, and biology of serrated polyps (SPs) of the colon has created considerable confusion among pathologists. According to the latest WHO classification, the family of SPs comprises hyperplastic polyps (HPs), sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas (TSAs). The term SSA/P with dysplasia has replaced the category of mixed hyperplastic/adenomatous polyps (MPs). The present study aimed to evaluate the reproducibility of the diagnosis of SPs based on currently available diagnostic criteria and interactive consensus development. In an initial round, H&E slides of 70 cases of SPs were circulated among participating pathologists across Europe. This round was followed by a consensus discussion on diagnostic criteria. A second round was performed on the same 70 cases using the revised criteria and definitions according to the recent WHO classification. Data were evaluated for inter-observer agreement using Kappa statistics. In the initial round, for the total of 70 cases, a fair overall kappa value of 0.318 was reached, while in the second round overall kappa value improved to moderate (kappa = 0.557; p < 0.001). Overall kappa values for each diagnostic category also significantly improved in the final round, reaching 0.977 for HP, 0.912 for SSA/P, and 0.845 for TSA (p < 0.001). The diagnostic reproducibility of SPs improves when strictly defined, standardized diagnostic criteria adopted by consensus are applied.

Evaluation of apoptosis along with BCL-2 and Ki-67 expression in patients with intestinal metaplasia.

The primary aim is to compare individuals with intestinal metaplasia (IM), chronic active gastritis (CAG), and normal gastric mucosa (NGM) in terms of apoptosis, proliferation, and Bcl-2 expression. The secondary aim is to determine whether these parameters are different between patients with and without gastric cancer in first-degree relatives. We enrolled 106 patients whose histopathological results were consistent with IM (n: 42), CAG (n: 51), or NGM (n: 13). Antral biopsies were immunohistochemically stained for Bcl-2 and Ki-67 expression. Apoptosis was detected using TUNEL assay. While no significant difference was determined between three groups with regard to apoptosis and Bcl-2 expression (p>0.05), Ki-67 expression was significantly higher in the IM group when compared with the CAG and NGM groups (29.90±22.87 vs. 18.18±16.22 vs. 18.54±20, respectively; p=0.012). Helicobacter pylori was determined to increase apoptosis (49.3% vs. 25.7%, p<0.05), nevertheless, it had no significant effect on proliferation and Bcl-2 expression. Bcl-2 and Ki-67 expression and apoptosis were not different among patients with and without a history of gastric cancer in first degree relatives. Although intestinal metaplasia cases demonstrate an increase in proliferation, no elevation is observed in apoptosis. This can be an important factor in the progression to gastric cancer.