Assessment of the risk and characterization of non-melanoma skin cancer in Kindler syndrome: study of a series of 91 patients

Abstract

Background Kindler Syndrome (KS) is a rare genodermatosis characterized by skin fragility, skin atrophy, premature aging and poikiloderma. It is caused by mutations in the FERMT1 gene, which encodes kindlin-1, a protein involved in integrin signalling and the formation of focal adhesions. Several reports have shown the presence of non-melanoma skin cancers in KS patients but a systematic study evaluating the risk of these tumors at different ages and their potential outcome has not yet been published. We have here addressed this condition in a retrospective study of 91 adult KS patients, characterizing frequency, metastatic potential and body distribution of squamous cell carcinoma (SCC) in these patients. SCC developed in 13 of the 91 patients. Results The youngest case arose in a 29-year-old patient; however, the cumulative risk of SCC increased to 66.7% in patients over 60 years of age. The highly aggressive nature of SCCs in KS was confirmed showing that 53.8% of the patients bearing SCCs develop metastatic disease. Our data also showed there are no specific mutations that correlate directly with the development of SCC; however, the mutational distribution along the gene appears to be different in patients bearing SCC from SCC-free patients. The body distribution of the tumor appearance was also unique and different from other bullous diseases, being concentrated in the hands and around the oral cavity, which are areas of high inflammation in this disease. Conclusions This study characterizes SCCs in the largest series of KS patients reported so far, showing the high frequency and aggressiveness of these tumors. It also describes their particular body distribution and their relationship with mutations in the FERMT-1 gene. These data reinforce the need for close monitoring of premalignant or malignant lesions in KS patients.

Inherited epidermolysis bullosa: update on the clinical and genetic aspects

“…KEB has autosomal recessive inheritance and is caused by changes in the FERMT1 gene, which encodes kindlin-1, a protein associated with integrins and focal adhesions. 98 , 99 In the skin, kindlin-1 is located next to the basal keratinocytes and acts as a protein that adapts the focal adhesions, linking the actin filaments to the membrane proteins. 97 , 100 In KEB patients, keratinocytes become disorganized, losing their characteristic structure and polarization, and their proliferation is reduced.…”

Epidermolysis Bullosa-Associated Squamous Cell Carcinoma: From Pathogenesis to Therapeutic Perspectives

“…Recently, Guerrero-Aspizua and coll. analyzed a cohort of 91 KS patients, 69 previously published [147,149], and 22 unpublished cases, in order to evaluate the incidence of SCC in KS syndrome at different ages [150]. 14.3% of the patients (13 out of 91) developed 1 or more well-differentiated SCC, for a total of 26 SCCs (25 in the skin and 1 in the oral mucosa).…”

“…Seven out of 13 KS patients with SCC presented metastases. Similar to other EB-related SCC, KS-SCCs are aggressive and represent the cause of death in 38.5% of patients [150].…”

Humanization of Tumor Stroma by Tissue Engineering as a Tool to Improve Squamous Cell Carcinoma Xenograft

“…Many of the aggressive SCC of the skin develops in areas with chronic ulcers as in hereditary conditions like epidermolysis bullosa [13,14,26]. The reason for this different behavior is still a subject of controversy and collaborative studies have recently shed light onto the matter [9,17,[27][28][29]. Recently, attention has been focused on a possible role of the stroma.…”