ABSTRACT
AIM: The rate of rectal cancer locoregional recurrence following radical surgery varies from 4% to 33%. Though the causes are unclear, likely factors include microscopic tumor residues in the lymphatics, positive resection margins and exfoliation of tumor cells and their subsequent intraluminar spread during operation. Other significant factors include type and technique of surgical procedure. Recently, it has been demonstrated that local recurrence may also be associated with the biological behaviour of the tumor and/or with the composition of the cellular microenvironment which creates optimal conditions for the growth and spread of tumor cells. CASE REPORT: The presented case here is interesting because the tumour recurred early following a curative surgical procedure with negative resection margins, without positive lymph nodes, without infiltration of the pelvic wall and without distant metastases. CONCLUSION: In patients with a determined risk of genetically altered tumor field encompassing epithelial or stromal changes, a different treatment strategy, including gene therapy, anti-inflammatory or anti-angiogenic therapy should be chosen to minimize increased tumor risk.
Subject(s)
Rectal Neoplasms/pathology , Rectal Neoplasms/surgery , Tumor Microenvironment , Aged , Female , Humans , Neoplasm Recurrence, Local , Neoplastic Cells, Circulating/pathologyABSTRACT
We report the expression of Snail-1, E-cadherin and claudin-1 by indirect immunohistochemistry in colonic neoplasia. Snail-1 is a zinc finger transcription factor expressed in cells that already have undergone almost complete epithelial-mesenchymal transition (EMT) and have already evaded from the tumor. The main mechanism by which Snail induces EMT is downregulation of E-cadherin, of which expression was shown to be frequently downregulated in many different types of tumors, where it accompanies the invasiveness and metastatic behavior of malignant cells. Moreover, Snail-1 may downregulate the expression of claudin-1, a cell-cell adhesion protein which plays a likely role in progression and dissemination during tumorigenesis. Snail-1 was expressed in both carcinoma and adenoma cells with histologically normal epithelium in the mucosa, adjacent to the tumors, without significant differences, and predominant strong intensity of staining. Statistically significant differences were revealed between normal and tumorous epithelium (p = 0.003) at the subcellular level, where the shift of the protein to the cytoplasm with combined cytoplasmic/nuclear or pure cytoplasmic expression was observed. E-cadherin expression was present in 100% of cases of both adenocarcinomas and adenomas, with prevailing strong membranous immunoreactivity and no differences between protein expression in tumors and normal mucosa. Predominating strong positivity of claudin-1 was detected in tumor cells of adenocarcinomas and adenomas. Marked differences were seen in protein localization, where membranous staining, typical for nontumorous epithelium, changed to combined membranous/cytoplasmic expression in adenocarcinomas (p = 0.0001) and adenomas (0.0002), in which cytoplasmic shift was associated with a higher degree of dysplasia. Furthermore, membranous/cytoplasmic localization was more frequent in the carcinoma group (87%) in comparison with adenomas (51%) (p = 0.0001). We conclude that dystopic subcellular localizations of Snail-1 and claudin-1 may participate in changes of cellular morphology and behavior which might be associated with altered effectory pathways of proteins and thus substantially contribute to the cancer development.
Subject(s)
Adenoma/metabolism , Cadherins/biosynthesis , Carcinoma/metabolism , Claudin-1/biosynthesis , Colorectal Neoplasms/metabolism , Gene Expression Regulation, Neoplastic , Neoplasm Proteins/biosynthesis , Transcription Factors/biosynthesis , Adenoma/pathology , Carcinoma/pathology , Colorectal Neoplasms/pathology , Epithelial-Mesenchymal Transition , Female , Humans , Male , Snail Family Transcription FactorsABSTRACT
BACKGROUND: Nestin is one of the intermediate filaments that are expressed in proliferating neural progenitor cells during development of the central nervous system (CNS) and peripheral nervous system. Postnatal re-expression of the protein occurs mainly under pathological conditions, including injury and neoplasia. In this study, nestin expression was detected in both benign and malignant melanocytic skin lesions and its diagnostic relevance was then evaluated. METHODS: Altogether 139 bioptic tissue samples consisting of 42 nodular melanomas, 32 superficial spreading melanomas, 12 metastatic melanomas, 10 dysplastic nevi and 43 common melanocytic intradermal and dermoepidermal nevi were analysed using indirect immunohistochemical staining. RESULTS: We demonstrated that nestin immunostaining was significantly increased in melanomas where it correlated with more advanced stages of the disease. CONCLUSION: We conclude that expression of the intermediate filament protein nestin might be an indicator of tumor dedifferentiation and more aggressive behaviour. Furthermore, we suggest that nestin might be a relevant marker of tumorous and non-tumorous angiogenesis.
Subject(s)
Biomarkers, Tumor/analysis , Intermediate Filament Proteins/biosynthesis , Melanoma/metabolism , Nerve Tissue Proteins/biosynthesis , Nevus, Pigmented/metabolism , Skin Neoplasms/metabolism , Humans , Immunohistochemistry , Melanoma/blood supply , Neovascularization, Pathologic/metabolism , Nestin , Nevus, Pigmented/blood supply , Skin Neoplasms/blood supplyABSTRACT
BACKGROUND: Trichofolliculomas and trichoepitheliomas are benign skin neoplasms originating from hair follicle cells. They result from defects in the signaling pathways that regulate hair follicle morphogenesis and regeneration. Thus they seem to be an excellent model of these processes. It is known that the E-cadherin/beta-catenin system of adhesion molecules plays a crucial role in the maintenance of tissue architecture. AIM: The aim of the present study was to investigate their involvement in benign hair follicle tumor development. METHODS: Semiquantitative intensity of expression were examined in formalin-fixed and paraffin-embedded tissue sections of 53 trichoepitheliomas, 15 trichofolliculomas and 19 normal skin samples by indirect immunohistochemistry. RESULTS: The intensity of E-cadherin/beta-catenin expression in tumor cells did not differ from controls. However, normal hair follicles cells exhibited membranous E-cadherin/beta-catenin expression, whereas both types of tumors, particularly trichoepitheliomas, showed E-cadherin/beta-catenin expression with a predominantly cytoplasmic localization. CONCLUSIONS: We suggest that this dystopic distribution of the E-cadherin/beta-catenin complex in hair follicle tumor cells may be a marker of cell-cell adhesion disruption which may contribute to the tumor formation.
Subject(s)
Cadherins/analysis , Hair Diseases/metabolism , Neoplasms, Basal Cell/chemistry , Skin Neoplasms/chemistry , beta Catenin/analysis , Humans , ImmunohistochemistryABSTRACT
Peroxisome proliferator-activated receptors (PPARs) are subgroups of nuclear hormonal receptors of transcripting factors mostly found in adipose tissue. They are described as important regulators of lipid and saccharide metabolism including insulin sensitivity; therefore they are taken as marker of metabolic syndrome. Their synthetic ligands could be used as drugs for insulin resistance and type 2 diabetes mellitus.