Short- and long-term impact of cancer on employment and financial outcomes of adolescents and young adults (AYAs): a large population-based case-control registry study in the Netherlands.

BACKGROUND: Adolescent and young adult (AYA) cancer survivors, 18-39 years at initial cancer diagnosis, often self-report negative consequences of cancer (treatment) for their career. Less is known, however, about the objective impact of cancer on employment and financial outcomes. This study examines the employment and financial outcomes of AYA cancer survivors with nationwide population-based registry data and compares the outcomes of AYAs with cancer with an age- and sex-matched control population at year of diagnosis, 1 year later (short-term) and 5 years later (long-term). PATIENTS AND METHODS: A total of 2527 AYAs, diagnosed in 2013 with any invasive tumor type and who survived for 5 years, were identified from the Netherlands Cancer Registry (clinical and demographic data) and linked to Statistics Netherlands (demographic, employment and financial data). AYAs were matched 1 : 4 with a control population based on age and sex (10 108 controls). Analyses included descriptive statistics, chi-square tests, independent samples t-tests, McNemar tests and logistic regression. RESULTS: AYA cancer survivors were significantly less often employed compared with their controls 1 year (76.1% versus 79.5%, P < 0.001) and 5 years (79.3% versus 83.5%, P < 0.001) after diagnosis, and received more often disability benefits (9.9% versus 3.1% 1 year after diagnosis, P < 0.001; 11.2% versus 3.8% 5 years after diagnosis, P < 0.001). Unemployed AYAs were more often diagnosed with higher disease stages (P < 0.001), treated with chemotherapy (P < 0.001), radiotherapy (P < 0.001) or hormone therapy (P < 0.05) and less often with local surgery (P < 0.05) compared with employed AYAs 1 and 5 years after diagnosis. CONCLUSION: Based on objective, nationwide, population-based registry data, AYAs' employment and financial outcomes are significantly affected compared with age- and sex-matched controls, both short and long-term after cancer diagnosis. Providing support regarding employment and financial outcomes from diagnosis onwards may help AYAs finding their way (back) into society.

Collaboration and Networking.

Awareness of the need for collaboration across pediatric and adult cancer to care for adolescents and young adults (AYAs) arose from the recognition of the unique characteristics of AYAs with cancer. Neither pediatric nor adult oncology hospital departments are able to provide age-appropriate care single handedly. The best way to bridge the gap in care of AYA cancer patients is to centralize aspects of their care within dedicated AYA care programs, including the following essential components: provision of developmentally appropriate and multidisciplinary (supportive) care, availability of AYA inpatient and outpatient facilities and healthcare professional AYA expertise as collaboration between adult and pediatric departments. Barriers are related to the slowly emerging evidence of benefit, cultural differences (collaboration between pediatric and adult oncology professionals), administrative and logistic challenges (small number of AYAs makes it difficult to create an AYA program in every hospital) and financial aspects (dependency on philanthropic funds). The sustainable development of an AYA program requires acceptance as a standard of care at the clinical and patient community and at government level. To improve the quality, equity and quantity of research and innovation in AYA cancer care across the world, it is necessary to join forces and collaborate in international networks to study issues such as the features of quality care, collaboration between pediatric and adult clinical teams, trial groups and professional societies, and AYA-specific groups such as Critical Mass, Canteen or European Network for Teenagers and Young Adults with Cancer.

CD44 isoforms, including the CD44 V3 variant, are expressed on endothelium, suggesting a role for CD44 in the immobilization of growth factors and the regulation of the local immune response.

Endothelium plays a central role in the regulation of site and inflammation specific leukocyte migration. Some of the mediators involved in leukocyte migration, such as chemokines, can bind to heparan sulfate on the endothelium resulting in immobilization near their sites of production. Because CD44 variants expressing V3 have been shown to carry heparan sulfate side chains and to interact through these side chains with heparan sulfate binding growth factors, we investigated the expression of CD44 variants on endothelium. We found a strong expression of V5, V7-8 and V10 CD44 variants and a weaker expression of V3 and V6 CD44 variants on endothelium by using immuno-histochemistry and by FACS analysis. Expression of CD44 V3 variants was confirmed at both the protein and mRNA levels by Western blotting and by reverse transcriptase-PCR respectively. Expression of CD44 variants was unaffected by IL-1beta, IL-8, TNFalpha, IFNgamma or IL-4 treatment, indicating either constitutive expression of these variants or involvement of other cytokines in their regulation.

Adhesion molecules in the dissemination of non-Hodgkin's lymphomas.

Most non-Hodgkin's lymphomas (NHLs) express a number of different adhesion receptors. A large body of evidence indicates that these adhesion receptors not only regulate normal lymphocyte trafficking but also play a pivotal role in the dissemination of NHL. Thus, cutaneous lymphocyte antigen, alpha 4 beta 7, alpha E beta 7, and L-selectin, which mediate the tissue-specific positioning of normal lymphocytes in the skin, mucosa, epithelium and lymph nodes, respectively, are selectively expressed on lymphomas localized at these sites. Furthermore, expression of CD44, a family of adhesion receptors with pleiotropic effects on tumor behavior, is related to lymphoma aggressiveness and dissemination. Taken together, these findings offer a framework for the understanding of tumor dissemination in NHL. In view of the similarities between lymphocyte behavior and the metastatic behavior of solid tumors, these insights might contribute to the understanding of the basic mechanisms underlying tumor metastasis in non-lymphoid tumors.

Binding of cell-surface expressed CD44 to hyaluronate is dependent on splicing and cell type.

CD44 is a major cell-surface receptor for hyaluronate (HA). By alternative RNA-splicing a large number of CD44 variants are generated. To explore the role of CD44 splicing in the regulation of cell binding to HA, three different isoforms of CD44 were transfected in the CD44 negative B-cell lymphoma line Namalwa and in the fibroblastoid cell line COS7. We observed that whereas the standard form of CD44 (CD44s) mediated adhesion of Namalwa to HA, Namalwa transfected with CD44v3-10 or CD44v8-10 was unable to bind to either immobilized or soluble HA. After stimulation of CD44 with an activating anti-CD44 mAb or with phorbol ester, the binding of CD44s to HA was 5- to 10-fold higher than that of the other two isoforms. By contrast, COS7 cells transfected with CD44s, CD44v8-v10, or CD44v3-v10 bound equally effectively to HA. Hence, in addition to alternative splicing, cell type determines CD44 binding to HA.

Expression of CD44 splice variants in human cutaneous melanoma and melanoma cell lines is related to tumor progression and metastatic potential.

Expression of CD44, particularly of certain splice variants, has been linked to tumor progression and metastasis formation in a number of different animal and human cancers. Because human cutaneous melanoma is among the most aggressive human cancers, we explored expression of CD44 isoforms (CD44v) in lesions of melanocytic tumor progression. In addition, by RT-PCR and FACS analysis we assessed CD44v RNA species and cell surface expression of CD44v in cultured melanocytes isolated from human foreskin and in a panel of 2 non-, 2 sporadically and 2 highly metastatic human melanoma cell lines. We observed that all melanocytic lesions examined showed strong uniform expression of standard CD44 (CD44s) epitopes. We did not detect CD44v6 expression in the melanocytic lesions. However, CD44 isoforms containing v5 or v10 were differentially expressed. V5 was expressed in 16%, 0%, 20%, 67% and 58% of common nevi, atypical nevi, early primary melanomas (< or = 1.5 mm), advanced primary melanomas (> 1.5 mm) and metastases, respectively, and hence was related to tumor progression. In contrast, CD44v10 was expressed in all common nevi, whereas part of the atypical nevi and most primary melanomas and metastases lacked v10. CD44v RNA patterns were closely similar in cultured melanocytes and all melanoma cell lines. Melanocytes expressed high levels of CD44s but no CD44v, whereas all melanoma cell lines expressed CD44v at the surface. Interestingly, expression of v5 was strongly increased in the highly metastatic cell lines. Our results suggest a role for CD44 variant domains, particularly v5 and v10, in human melanocytic tumor progression.