Spotlight

Abstract

Hoevenaars et al., pp. 2767–2773 Vulvar squamous cell carcinoma (SCC) makes up 3% to 5% of all female genital cancers and falls into two categories: the typical keratinizing vulvar squamous carcinomas seen in older women and the human papilloma virus (HPV)-positive basaloid and warty carcinomas in younger women. Both types are preceded by specific vulvar intra- epithelial neoplasia (VIN). Differentiated VIN, a precursor to keratinizing vulvar SCC, is seen most frequently in older women with lichen sclerosus or lichen simplex chronicus, and develops along an HPV-independent pathway. It can be difficult to distinguish a benign vulvar lesion from normal epithelium. VIN is often multifocal, occurs in younger women and is associated with smoking and HPV, predominantly HPV-16 and 18, and carries a much lower risk of progressing to invasive carcinoma. Hoevenaars et al. tested 75 differentiated VIN lesions with adjacent SCC and 45 usual VIN lesions for HPV DNA and the immunohistochemical expression of MIB1, a proliferation marker, and for p16INK4, a marker for HPV infection, and p53, which is frequently detected in vulvar SCC and differentiated VIN, most likely because of cellular accumulation of the mutated, abnormal protein. All differentiated VINs were HPV and p16INK4 negative and MIB1 expression was confined to the parabasal layer (96%), while 84% of all usual VINs tested positive for HPV, p16INK4 and MIB1, confirming that two separate pathways with unique immunohistochemical profiles lead to the development of vulvar SCC. Being able to readily distinguish between the two types of VIN should facilitate recognition of differentiated VIN lesions and thus a more effective treatment strategy for this lesion. Conrotto et al., pp. 2856–2864 Targeted tumor therapy enables bioactive molecules to destroy cancer cells while leaving normal cells unharmed. The success of this strategy hinges on the ability of specific tumor antigens to enable selective antibodies to home in on their tumor targets. Conrotto et al. recently developed a new protein-based method for identifying antigens accessible from the bloodstream of tumor-bearing mice. The biotinylated proteins are then isolated, proteolytically digested and analyzed by comparative mass spectroscopy. In the current study, they extended this approach to ex vivo perfusion of surgically resected human colon cancer to identify tumor antigens expressed in the neo-vasculature and the surrounding stroma. The method identified a total of 367 proteins, 67 of which were overexpressed in colon cancer, whereas 121 could only be detected in normal colon tissue. Focusing on the most promising candidates, the authors used transcriptomic and immunohistochemical analysis to confirm the overexpression of Cathepsin G, Emilin-1, NGAL, also known as Lipocalin 2, and GW112, a recently identified protein, which is overexpressed in stomach, pancreas, lung and colon tumors. Human monoclonal antibodies generated against GW112 revealed strong expression in 64% of the colon cancers and 60% of breast cancers analyzed, paving the way to determining whether it could serve as a suitable target for antibody-based delivery strategies. Tumor-associated antigens that can be easily reached from the tumor neo-vasculature are particularly attractive targets for intravenously administered antibody-based therapeutic agents. Two-color immunoflourescence of colon cancer tissue. Sections were stained with anti-NGAL (a), or anti-GW112 (b,c) antibodies, together with the anti-von Willebrand Factor antibody (d–f). Merged panels (g–i) show the presences of both antigens in the proximity of blood vessels. A larger number but not all blood vessels express the antigens, as indicated by the asterisks in panel h. Madanat et al., pp. 2891–2898 Just 30 years ago, the prognosis was grim for children with cancer. Today, thanks to remarkable advances in treatment, many survive into adulthood, resulting in a growing population of cancer survivors, though the effect that treatment may have on their ability to have a family later in life is uncertain. To evaluate the probability of parenthood among cancer survivors, the authors identified cancer patients ages 0–34 years at diagnosis from the Finnish Cancer registry (N = 25,784) and their siblings (N = 44,611) by recording linkage and compared the relative probabilities of parenthood for first and second births for male and female survivors by age group (0–14, 15–19 and 20–34 years at diagnosis) and cancer type. The overall probability of post-treatment parenthood was significantly reduced by about 50 % in cancer patients compared with siblings. However, the probability of having a second child after diagnosis, having already parented one child following diagnosis, was only slightly reduced. Among males, the relative probability of parenthood was significantly higher among adolescent cancer survivors than in adult and childhood age groups. In females, the relative probability of parenthood was similarly reduced among pediatric and adolescent cancer survivors, while adult cancer survivors faced significantly reduced fertility. Further research will be needed to study the impact of newer treatments and to provide adequate and tailored family planning counseling for a growing number of cancer survivors hoping to maintain their fertile potential.