Immunomodulatory drugs have demonstrated efficacy in the therapy against autoimmune diseases such as rheumatoid arthritis, Crohn's disease or ulcerative colitis. Tumor necrosis factor‐α (TNF‐α) ...represents a target molecule for the treatment of these entities. Use of monoclonal antibodies can block the proinflammatory function of TNF‐α. It has been shown that this action can reactivate quiescent chronic diseases as well as modify the immune response or potentiate carcinogens, thereby increasing the risk of secondary tumor development. In this context, different types of solid or hematological tumors have been documented. We present the case of a male with chronic ulcerative colitis who secondarily developed a cutaneous Hodgkin‐type lymphoproliferative lesion associated with immunodeficiency. This secondary tumor developed after 6 months of treatment with anti‐TNF‐α.
Vieites B, Avila R, Biscuola M, Carvajo F. Cutaneous Hodgkin‐type lymphoproliferative lesion associated with immunomodulatory therapy for ulcerative colitis.
Aims
Neoadjuvant therapy is used in many patients with breast cancer before surgery, with the aim of reducing the tumour size, allowing conservative resections. Sentinel node biopsy is a conservative ...procedure for handling the axilla in breast cancer; however, the use of this technique after neoadjuvant treatment is under discussion. For sentinel node assay, methods based on the detection of cytokeratin 19 (CK19) mRNA, such as one‐step nucleic acid amplification (OSNA), are available. However, if systemic therapy could alter protein expression, then CK19 would not be a good target for analysing these nodes. The aim of this study was to evaluate the immunohistochemical expression of CK19 within different cancer types, and to compare its expression in breast tumours and axillary nodes before and after treatment.
Methods and results
CK19 immunostaining was studied in 162 tumour and node samples before and after treatment. Statistical studies using the McNemar test and chi‐square test were performed. CK19 expression was found in 155 cases. We compared CK19 expression in tumour and node biopsies before and after treatment, and we found a lack of significant CK19 expression changes.
Conclusions
Our study has confirmed the preservation of CK19 protein expression in breast cancer cells after neoadjuvant therapy. On the basis of these results, quantification‐based methods such as the OSNA CK19 assay, could be an accurate tool with which to analyse the sentinel nodes, regardless of whether they had been obtained before or after treatment.
Summary The molecular events implicated in the development of endometrial carcinosarcoma remain poorly understood. Using complementary DNA microarrays, we analyzed a group of 15 endometrial ...carcinosarcomas and compared their gene expression profiles with those obtained from a group of 23 endometrioid endometrial carcinomas. We demonstrated changes in the expression of genes modulating processes such as the epithelial to mesenchymal transition, muscle differentiation, the expression of cancer/testis antigens, and immune response in endometrial carcinosarcomas. The high mobility group AT-hook 2 gene is an embryonic nuclear factor that mediates epithelial to mesenchymal transition in various tumor models, and it was among the genes overexpressed in endometrial carcinosarcomas. High mobility group AT-hook 2 overexpression was confirmed in 54% of endometrial carcinosarcomas by quantitative real time–polymerase chain reaction and immunohistochemistry. Moreover, we found a significant inverse correlation between the expression of high mobility group AT-hook 2 and let-7b, a member of the let-7 family of microRNAs that represses high mobility group AT-hook 2 expression. These changes were also associated with overexpression of Lin28B , a suppressor of microRNA biogenesis that is implicated in cancer progression and metastasis. Finally, high mobility group AT-hook 2 overexpression, which was detected in less than 3% of endometrioid endometrial carcinomas, was observed in many nonendometrioid carcinomas (46% of 28 samples). This pattern of expression, restricted to nonendometrioid carcinomas and endometrial carcinosarcomas, reflects a role for high mobility group AT-hook 2 in endometrial carcinogenesis that is associated with aggressive phenotypes and points to its potential use as a marker to distinguish between endometrioid and nonendometrioid tumors.
Immunomodulatory drugs have demonstrated efficacy in the therapy against autoimmune diseases such as rheumatoid arthritis, Crohn's disease or ulcerative colitis. Tumor necrosis factor- alpha (TNF- ...alpha ) represents a target molecule for the treatment of these entities. Use of monoclonal antibodies can block the proinflammatory function of TNF- alpha . It has been shown that this action can reactivate quiescent chronic diseases as well as modify the immune response or potentiate carcinogens, thereby increasing the risk of secondary tumor development. In this context, different types of solid or hematological tumors have been documented. We present the case of a male with chronic ulcerative colitis who secondarily developed a cutaneous Hodgkin-type lymphoproliferative lesion associated with immunodeficiency. This secondary tumor developed after 6 months of treatment with anti-TNF- alpha .Original Abstract: Vieites B, Avila R, Biscuola M, Carvajo F. Cutaneous Hodgkin-type lymphoproliferative lesion associated with immunomodulatory therapy for ulcerative colitis.
The human oxidised low-density lipoprotein receptor 1 (OLR1) gene is a functional candidate for atherosclerosis. An association of the OLR1 gene with acute myocardial infarction (AMI) or coronary ...artery disease (CAD) has recently been reported. In the present study a total of 677 Italian subjects, 327 CAD-free, 350 CAD, of which 190 with AMI and 160 AMI-free, was genotyped for the following four OLR1 single nucleotide polymorphisms: exon 4 K167N, IVS4 -73C>T, IVS4 -14A>G, and 3'UTR 188 C>T. No statistically significant difference was observed in allele or genotype distribution of the exon 4, intron 4, or 3'UTR SNPs in CAD patients compared to CAD-free subjects, or within CAD, in AMI patients compared to AMI-free patients. A correlation was found between the K167N G/G genotype and the increased number of obstructed vessels. Even if the OLR1 genotype frequency distribution data in CAD or AMI subjects here reported do not fully confirm the positive results of some other association studies, an association with a marker of CAD severity was observed.
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