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1.
Rom J Morphol Embryol ; 62(4): 971-979, 2021.
Article in English | MEDLINE | ID: mdl-35673816

ABSTRACT

BACKGROUND AND AIM: Colonic serrated lesions are premalignant lesions, using an alternative malignization pathway, including multiple genetic and epigenetic alterations, as: mismatch repair deficiency due to MutL homolog 1 (MLH1) promoter methylation, tumor protein p53 (TP53) mutations, activating mutations of v-Raf murine sarcoma viral oncogene homolog B (BRAF) and Kirsten rat sarcoma viral oncogene homolog (KRAS). Our study aims to evaluate MLH1, BRAF and p53 immunohistochemical (IHC) status in sessile serrated lesions (SSLs), with and without dysplasia. MATERIALS AND METHODS: This is a retrospective case-control study including 20 SSLs with dysplasia and 20 SSLs without dysplasia (matching sex and age). IHC expression of MLH1, BRAF and p53 was evaluated as the percent of nuclear loss of MLH1, cytoplasmic positivity of BRAF and nuclear positivity of p53. Data concerning age, sex, localization of the lesion, dysplasia and IHC results were statistically processed using Microsoft Excel. RESULTS: We had very polymorphous patterns of IHC expression for BRAF, MLH1 and p53, especially in the dysplastic group. Thus, two patients were BRAF+∕MLH1-∕p53+, three were BRAF+∕MLH1-∕p53-, one was BRAF+∕MLH1+∕p53- and six were BRAF+∕MLH1+∕p53+. Dysplastic lesions without BRAF mutation exhibited the following phenotype: one case BRAF-∕MLH1-∕p53+, four BRAF-∕MLH1-∕p53- and three BRAF-∕MLH1+∕p53+. In the control group (SSLs without dysplasia), there was a more homogenous distribution of cases: eight cases BRAF+∕MLH1+∕p53-, seven BRAF-∕MLH1+∕p53-, one BRAF-∕MLH1-∕p53+, two BRAF-∕MLH1-∕p53- and two BRAF-∕MLH1+∕p53+. CONCLUSIONS: There are more routes on the serrated pathway, with different mutations and time of acquisition of each genetic or epigenetic lesion with the same morphological result. These lesions should be stratified according to their risk to poor outcome and their need to further surveillance.


Subject(s)
Adenocarcinoma , Adenoma , Colonic Polyps , Colorectal Neoplasms , Tumor Suppressor Protein p53/metabolism , Adenocarcinoma/pathology , Adenoma/pathology , Animals , Case-Control Studies , Colonic Polyps/pathology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Humans , Hyperplasia , Mice , MutL Protein Homolog 1/genetics , Mutation/genetics , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Retrospective Studies , Tumor Suppressor Protein p53/genetics
2.
Rom J Intern Med ; 54(2): 113-20, 2016.
Article in English | MEDLINE | ID: mdl-27352440

ABSTRACT

Mast cells proteases, tryptase and chymase are directly involved in the growth and progression of solid tumors due to their important role in tumor angiogenesis. We examined the density of tryptase positive mast cells and the mean density of new blood vessels in gastric malignant tumors of patients with and without Helicobacter pylori infection, using immunohistochemical staining for tryptase (for mast cells) and CD 105 (for new vessels). Tryptase and CD 105 expression was detected in gastrectomy specimens. In this study, mast cell density correlates with angiogenesis and the growth and progression of gastric cancer. It also shows that the participation of Helicobacter pylori infection in the growth and progress of gastric neoplasia is due to an increase of peritumoral angiogenesis, with subsequent local and distant tumor spread and perivascular growth, but without perineural and nodal involvement.


Subject(s)
Adenocarcinoma/enzymology , Adenocarcinoma/pathology , Antigens, CD/metabolism , Biomarkers, Tumor/metabolism , Mast Cells/metabolism , Neovascularization, Pathologic , Receptors, Cell Surface/metabolism , Stomach Neoplasms/enzymology , Stomach Neoplasms/pathology , Tryptases/metabolism , Adenocarcinoma/metabolism , Adenocarcinoma/microbiology , Adenocarcinoma/surgery , Adult , Aged , Case-Control Studies , Endoglin , Female , Gastrectomy , Helicobacter Infections/complications , Helicobacter pylori/isolation & purification , Humans , Male , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Prognosis , Retrospective Studies , Risk Factors , Sensitivity and Specificity , Stomach Neoplasms/metabolism , Stomach Neoplasms/microbiology , Stomach Neoplasms/surgery
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