Expression of let-7a, miR-106b and miR-29b is changed in human gastric cancer.

MicroRNA (miRNA) are small, noncoding RNA sequences that post-transcriptionally regulate the proliferation, activity and apoptosis of human gastric cancer cells by controlling various signaling cascades. Processes that involve miRNA molecules can create a specific network of interactions in a cell, and disruption of its functioning may contribute to the transformation of normal cells into cancerous cells. Aims of our survey were: 1) study the relationship between the expression of selected miRNA types (let-7a, miR-106b, miR-29b, miR-21, miR-155, miR-222) in the gastric mucosa and pathomorphological changes determined by classical histopathological methods, 2) perform in silico analysis to select target genes for selected miRNAs and to perform functional analysis of these genes. Eighty-three subjects (45 women, 38 men; mean age 39±14 years, range: 21-80 years, were examined). Among them were 18 (21.5%) patients with chronic active gastritis, 42 (50.6%) people with chronic inactive gastritis, 9 (10.8%) patients with gastric cancer and 14 (16.9%) patients without histopathological changes. The study demonstrated that mainly the expression of 3 (miR-29b, let-7a miR-106b) out of 6 selected miRNAs are significantly different depending on the site of biopsy (body of the stomach or antrum) and the group of patients. Expression of miR-106b in the antrum and body was the highest in the group of cancer patients and the lowest in patients with chronic active gastritis. The expression of let-7a differed depending on group of patients and location. The highest expression was in the body in the group with inactive gastritis and the lowest in gastric cancer. Patients with cancer had the lowest expression of miR-29b in stomach body and it was the highest in the patients with inactive gastritis in this location. Expression of miR-21 and miR-155 determinations were not statistically significant in comparison to groups or locations, and of miR-222 was not different between the groups, but only in the control group was higher in the antrum than in the body. We conclude that identification of miRNAs may represent a promising modern complementary method in the diagnosis of gastric diseases, especially cancer.

Histopathological Revision for Gastroenteropancreatic Neuroendocrine Neoplasms in Expert Centers: Does It Make the Difference?

BACKGROUND: The correct histopathological diagnosis of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) is crucial for treatment selection and prognostication. It is also very challenging due to limited experience in nonexpert centers. Revision of pathology is standard of care for most patients who are referred to NEN expert centers. OBJECTIVES: To describe the clinical impact of histopathological revision for GEP-NEN patients referred to an expert center. METHODS: Retrospective multicenter analysis of all GEP-NENs receiving a histopathological revision in 6 European NEN expert centers (January 2016 to December 2016) to evaluate the impact on patient management. RESULTS: 175 patients were included and 14.7% referred for a second opinion. Histological samples were 69.1% biopsies, 23.4% surgical specimens, and 7.5% endoscopic resections. Histopathological changes due to revision included first assessment of Ki67 in 8.6% of cases, change in grading in 11.4% (3.4% G1 to G2; 5.7% G2 to G1; 0.6% G2 to G3; 1.7% G3 to G2), definition of tumor invasion in 10.8%, additional immunohistochemical staining in 2.3%, diagnosis of mixed adenoneuroendocrine carcinoma in 3.4%, exclusion of NEN in 3.4%, first diagnosis of NEN in 2.3%, and tumor differentiation for G3 in 1.7%. The revision had a clinical impact in 36.0% of patients, leading to a new therapeutic indication in 26.3%. The indication to then perform a new imaging test occurred in 21.1% and recommendation to follow-up with no further treatment in 6.3%. CONCLUSIONS: Histopathological revision in expert centers for NENs can change the diagnosis, with a significant clinical impact in about one third of patients.

The NETest liquid biopsy is diagnostic for gastric neuroendocrine tumors: observations on the blood-based identification of microscopic and macroscopic residual diseaseOK.

BACKGROUND: NETest, a novel multi-gene liquid biopsy has utility in neuroendocrine tumor (NET) diagnosis and identification of residual disease. We independently assessed utility of the NETest to diagnose gastric neuroendocrine neoplasms (GNENs) and identify micro- and macroscopic residual disease. METHODS: Cohorts comprised histologically confirmed GNENs at biopsy, n = 46; GNETs Type 1: 42 (32 NET G1, 10 NET G2), a GNET Type 3: 1 well-differentiated NET G3, neuroendocrine carcinomas (NECs) (n = 3), and controls (n = 63). Disease status at sampling was assessed by gastroscopy, histology (resection margin [R] positivity of polypectomy or biopsy), EUS, CT or MRI, and/or 68Ga-DOTA-TATE PET/CT. Groups included image- (gastroscopy, EUS, and anatomical and/or functional imaging) positive or image negative disease. NETest assay by PCR (spotted plates, normal cut-off: 20). DATA: mean ± SD. RESULTS: Disease extent: Image-negative (n = 30) (21 R0, 9 R1); Image-positive, n = 16. DIAGNOSIS: NETest was increased in GNETs (23 ± 11) vs. controls (7 ± 4, p < 0.0001). In histology-positive, the NETest accuracy was 100% (25/25). Microscopic disease: In image-negative but R1, NETest was elevated in 100% (9/9; 28 ± 9). Levels were elevated vs. controls (7 ± 4, p < 0.0001), or R0 (16 ± 11, p = 0.02). Eight of 21 R0, exhibited positive NETest. Macroscopic disease: Gastric lesions were multiple: 38%, single: 62%, submucosal: 13%, or ulcerated: 13%. Lesions size was ≤5 mm (50%), > 5-9.9 mm (17%), 10-19.9 mm (17%), ≥20 mm (17%) [≥10 mm: 34%). The NETest accuracy was 100% (16/16). Levels (28 ± 7) were higher than controls (7 ± 4, p < 0.0001) or R0 (16 ± 11, p = 0.002) but not to R1 (28 ± 9, p = 0.5). CONCLUSIONS: NETest is diagnostic for gastric NETs. Elevated levels identify both microscopic and macroscopic residual disease. In histology/image-negative disease, elevated NETest may reflect early evidence of increased neuroendocrine gene expression of hypergastrinemia-induced neoplastic transformation of enterochromaffin-like (ECL) cells to tumor status. A sensitive liquid biopsy has utility in the management and surveillance of gastric NET disease.

[Assessment of utility of nm 23 antigen as a metastatic potential marker in laryngeal cancers: preliminary study]. / Ocena przydatnosci oznaczania antygenu nm 23 jako markera potencjalu przerzutowego raków krtani--doniesienie wstepne.

The aim of the study was the analysis of the utility of nm 23 protein in prediction of cervical lymph node metastases in patients with laryngeal cancer. A preliminary study was performed in 35 patients with laryngeal cancer with cervical lymph node metastases, which were confirmed by histopathologist. The control group consisted of 30 patients with laryngeal cancer without cervical lymph node metastases. In statistical analysis T and N were taken into account. In the investigated group with metastases the presence of positive immunostaining was found in 11% of cases while in the control group in 20%. The analysis of the presence of nm 23 protein revealed a weak usefulness of this marker as a factor which predicts the presence of the cervical metastases.

Breast cancer progression and expression of blood group-related tumor-associated antigens.

There is sufficient evidence that blood group related Lewis antigens are tumor-associated molecules. We have conducted immunohistochemical analysis of the expression of Lewis antigens in breast cancer tissue as an indicator of the degree of malignancy and as a prognostic factor. The studies were performed by examining 43 female patients diagnosed with invasive ductal carcinoma of the breast. Postoperative specimens were stained immunohistochemically using a panel of monoclonal antibodies (MAbs) specific for tumor-associated antigens: sialosyl LewisA, LewisA, LewisB, Lewisx, and LewisY. The aims of the study were to compare the appearance of metastases, degree of cancer stage (pTNM), and its histologic differentiation with the expression of Lewis phenotype. The evaluation of antigen expression was performed quantitatively and independently by two pathologists. Statistical significance was defined by Mann-Whitney test. The presented analysis of Lewis antigens showed higher expression of LeB and LeA (p = 0.03) in patients in stage N2 than in stage N1. The expression of LeB and LeY was higher in patients in stage T4 than in stage T1 (p = 0.02). No differences were observed for histologic differentiation. These data suggest that the expression of sialosyl-LeA and LeB antigens in breast cancer may predict metastases to lymph nodes.

[Difficulties in diagnosis of cytomegalovirus mononucleosis syndrome]. / Trudnosci w rozpoznaniu zespolu mononukleozy cytomegalowirusowej.

A case of a healthy 23-year-old woman is reported with cytomegalovirus mononucleosis as a result of infection of cytomegalovirus probably primary. The patient presented with symptoms of generalized adenopathy, migratory arthralgias and arthritis, hepatosplenomegaly, long lasting rash as well as complications of pneumonia and myocarditis. Because on histopathological examination of lymph node the Hodgkin-Reed-Sternberg-like cells were found a misdiagnosis of Hodgkin's disease was initially made. After about 8 weeks period there was a complete recovery. The current problems related to cytomegalovirus infection are presented.