No abstract

Purpose Pathologic stage II melanoma patients have variable outcomes when divided by sub-stage. We hypothesized that an understanding of the patterns of initial relapse by sub-stage will better inform follow-up guidelines. Methods We performed a retrospective review of 738 adult patients with pathologic stage II cutaneous melanoma treated at Memorial Sloan Kettering Cancer Center between 1993 and 2013. Clinical records were reviewed to determine time, location, and method of detection of initial relapse. Results At a median follow-up of 52 months, 219 patients relapsed. Relapses were detected more frequently in higher sub-stages. Initial relapses were most commonly local/in-transit for IIA and IIB, and systemic for IIC. Lung and brain were the most frequent sites of systemic relapse. Patient-detection was the most common method of relapse detection (59%) in all sub-stages. The 5-year cumulative incidence for patient-detected relapse was 13.6% for IIA, 18.9% for IIB, and 23.3% for IIC, and for image-detected relapse was 3.4%, 7.9% and 16.6%, respectively. The 5-year cumulative incidence for physician-detected relapse was less than 10% across all sub-stages and leveled off at three years for stage IIA and IIB and two years for stage IIC. Conclusion Relapses were most frequently patient-detected in all stage II sub-stages, highlighting the importance of patient education and self-examination. The highest yield for routine imaging is in stage IIC patients during the first four years. Physician examination is unlikely to detect relapses beyond three years for stage IIA and IIB, and beyond two years for stage IIC patients.

The expression pattern of interferon-inducible proteins reflects the characteristic histological distribution of infiltrating immune cells in different cutaneous lupus erythematosus subsets.

Papillary thyroid cancer (PTC) is the most prevalent endocrine neoplasia. The increased incidence of PTC in patients with thyroiditis and the frequent immune infiltrate found in PTC suggest that inflammation might be a risk factor for PTC development. The CXCR3-ligand system is involved in thyroid inflammation and CXCR3 has been found upregulated in many tumors, suggesting its pro-tumorigenic role under the inflammatory microenvironment. CXCR3 ligands (CXCL4, CXCL9, CXCL10 and CXCL11) trigger antagonistic responses partly due to the presence of two splice variants, CXCR3A and CXCR3B. Whereas CXCR3A promotes cell proliferation, CXCR3B induces apoptosis. However, the relation between CXCR3 variant expression with chronic inflammation and PTC development remains unknown. Here, we characterized the expression pattern of CXCR3 variants and their ligands in benign tumors and PTC. We found that CXCR3A and CXCL10 mRNA levels were increased in non-metastatic PTC when compared to non-neoplastic tissue. This increment was also observed in a PTC epithelial cell line (TPC-1). Although elevated protein levels of both isoforms were detected in benign and malignant tumors, the CXCR3A expression remained greater than CXCR3B and promoted proliferation in Nthy-ori-3-1 cells. In non-metastatic PTC, inflammation was conditioning for the CXCR3 ligands increased availability. Consistently, CXCL10 was strongly induced by interferon gamma in normal and tumor thyrocytes.Our results suggest that persistent inflammation upregulates CXCL10 expression favoring tumor development via enhanced CXCR3A-CXCL10 signaling. These findings may help to further understand the contribution of inflammation as a risk factor in PTC development and set the basis for potential therapeutic studies.