Marcy Neuburg

The skin cancer index: clinical responsiveness and predictors of quality of life.

Objective: To establish the clinical responsiveness of the Skin Cancer Index (SCI), a new disease‐specific quality of life (QOL) instrument, and to assess demographic and clinical factors which impact QOL in patients with nonmelanoma skin cancer (NMSC).

Expression pattern of the bullous pemphigoid-180 antigen in normal and neoplastic epithelia

BP180 is a 180kDa hemidesmosomal protein recognized by bullous pemphigoid (BP) and pemphigoid gestationis (PG) autoantibodies. Recent cloning and sequence analysis performed by our laboratory have revealed that BP180 is a transmembrane protein with a long extracellular collagen‐like region. A rabbit polyclonal antibody has been generated against a recombinant protein, designated GST‐NΔ1. containing a segment of the BP180 ectodomain. The resulting antiserum. RNΔ1 A, was shown to specifically react with BP180 on immunoblot, and labelled the extracellular region of the epidermal hemidesmosome on immunoelectron microscopy. A panel of normal and neoplastic human tissues were analysed by indirect immunofluorescence (IF) and RNΔ1A, to determine the distribution of BP180. A total of nine basal cell carcinomas (BCCs) and four squamous cell carcinomas (SCCs) of the skin were also studied. Intense IF staining was seen along the basement membrane zone (BMZ) of the epidermis, hair follicles, and the periphery of sebaceous gland lobules. The sebaceous lobules showed more intense staining in areas close to the duct, The epithelial BMZ of the following tissues also reacted with RNΔ1A: cornea, ocular conjunctiva, buccal mucosa. upper oesophagus, placenta (amnion placentum). umbilical cord and transitional epithelium of the bladder, The epithelium of the jejunum and ovary tailed to react with RNΔ1A, Staining of the BCCs and SCCs was variable. Five of six nodular BCCs showed some anti‐BP180 staining at the tumour‐stromal interface, although the level of staining was less intense than that observed in the overlying normal epidermis. All three morphoeic BCCs analysed in this investigation did not show any staining with RNΔ1A. Three of four SCCs showed weak staining at the tumour‐stromal interface. Thus, the tissue distribution of BP180 paralleled that of hemidesmosomes, and expression of this protein was found to be decreased or absent in cutaneous neoplasms.

Creation of a quality of life instrument for nonmelanoma skin cancer patients.

Objective: Malignancies of the skin are the most common cancers among humans. The cervicofacial region is most affected by cutaneous malignancies, with approximately 80% of nonmelanoma skin cancers (NMSC) occurring in the head and neck. Treatment of cervicofacial skin cancers also is more likely to result in significant patient morbidity, because of the functional and cosmetic importance of this region. Unlike other malignancies, skin cancer has not been well investigated in terms of patient quality of life (QOL) assessment. Furthermore, no validated disease‐specific QOL instrument currently exists for skin cancer. The aim of this study was to construct a new QOL instrument, The Facial Skin Cancer Index (FSCI), that captures the relevant QOL issues for NMSC patients.

XPC INITIATION CODON MUTATION IN XERODERMA PIGMENTOSUM PATIENTS WITH AND WITHOUT NEUROLOGICAL SYMPTOMS

Two unrelated xeroderma pigmentosum (XP) patients, with and without neurological abnormalities, respectively, had identical defects in the XPC DNA nucleotide excision repair (NER) gene. Patient XP21BE, a 27-year-old woman, had developmental delay and early onset of sensorineural hearing loss. In contrast, patient XP329BE, a 13-year-old boy, had a normal neurological examination. Both patients had marked lentiginous hyperpigmentation and multiple skin cancers at an early age. Their cultured fibroblasts showed similar hypersensitivity to killing by UV and reduced repair of DNA photoproducts. Cells from both patients had a homozygous c.2T>G mutation in the XPC gene which changed the ATG initiation codon to arginine (AGG). Both had low levels of XPC message and no detectable XPC protein on Western blotting. There was no functional XPC activity in both as revealed by the failure of localization of XPC and other NER proteins at the sites of UV-induced DNA damage in a sensitive in vivo immunofluorescence assay. XPC cDNA containing the initiation codon mutation was functionally inactive in a post-UV host cell reactivation (HCR) assay. Microsatellite markers flanking the XPC gene showed only a small region of identity ( approximately 30kBP), indicating that the patients were not closely related. Thus, the initiation codon mutation resulted in DNA repair deficiency in cells from both patients and greatly increased cancer susceptibility. The neurological abnormalities in patient XP21BE may be related to close consanguinity and simultaneous inheritance of other recessive genes or other gene modifying effects rather than the influence of XPC gene itself.

Reduction of immunosuppression for transplant-associated skin cancer: Thresholds and risks

Background  Although evidence supports the efficacy of reducing immunosuppression for transplant‐associated skin cancer, clinical thresholds for and risks associated with reduction are not well defined.

Cutaneous keratocyst in naevoid basal cell carcinoma syndrome

Summary We report a patient with naevoid basal cell carcinoma syndrome (NBCCS) who developed cutaneous cysts on her digits. Histological examination of one of the cysts showed a festooned lining epithelium maturing without a granular cell layer, similar to that of the jaw keratocyst characteristic of this syndrome. This type of cutaneous keratocyst has been reported only once previously, in two patients with NBCCS.

Role of human papillomavirus in cutaneous oncogenesis

There is a strong association between the human papillomavirus and cutaneous squamous cell carcinoma. If this association was merely random, one would expect an equal distribution of human papillomavirus types among affected individuals. However, only specific types of human papillomavirus are consistently found in cutaneous and genital squamous cell carcinomas. Immunosuppressed individuals clearly have a much higher incidence of cutaneous carcinomas. Immunosuppression, either local or systemic, not only decreases immune surveillance but may also dictate the amount and type of virus each individual may carry. Epidermodysplasia verruciformis and other rare hereditary disorders that combine specific immune defects and an increased incidence of malignancy are very useful models that clearly fulfill a multistep theory of oncogenesis. The precise mechanism of oncogenesis in these select human papillomavirus types is not yet fully understood. Intracellular interactions with the recently described tumor suppressor proteins may prove to be the primary site of action of these oncogenic viruses. Environmental cocarcinogens and activation of oncogenes are clearly important if not essential factors in human papillomavirus-associated tumors. As our knowledge and understanding of malignant transformation grows, it becomes apparent that this is a complex multistep process.

MicroRNA-135b Regulates Leucine Zipper Tumor Suppressor 1 in Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin malignancy and it presents a therapeutic challenge in organ transplant recipient patients. Despite the need, there are only a few targeted drug treatment options. Recent studies have revealed a pivotal role played by microRNAs (miRNAs) in multiple cancers, but only a few studies tested their function in cSCC. Here, we analyzed differential expression of 88 cancer related miRNAs in 43 study participants with cSCC; 32 immunocompetent, 11 OTR patients, and 15 non-lesional skin samples by microarray analysis. Of the examined miRNAs, miR-135b was the most upregulated (13.3-fold, 21.5-fold; p=0.0001) in both patient groups. Similarly, the miR-135b expression was also upregulated in three cSCC cell lines when evaluated by quantitative real-time PCR. In functional studies, inhibition of miR-135b by specific anti-miR oligonucleotides resulted in upregulation of its target gene LZTS1 mRNA and protein levels and led to decreased cell motility and invasion of both primary and metastatic cSCC cell lines. In contrast, miR-135b overexpression by synthetic miR-135b mimic induced further down-regulation of LZTS1 mRNA in vitro and increased cancer cell motility and invasiveness. Immunohistochemical evaluation of 67 cSCC tumor tissues demonstrated that miR-135b expression inversely correlated with LZTS1 staining intensity and the tumor grade. These results indicate that miR-135b functions as an oncogene in cSCC and provide new understanding into its pathological role in cSCC progression and invasiveness.

EGFRvIII Expression in Squamous Cell Carcinoma of the Skin

EGFRvIII Expression in Squamous Cell Carcinoma of the Skin Cutaneous squamous cell carcinoma (SCC) is a common cancer with an estimated 200 000 new cases annually.1 It is usually readily curable. However, a small subset of SCC tumors (approximately 10%, or 20 000 cases annually), termed “highrisk SCC,” carries an elevated risk of metastasis and death and accounts for nearly all the mortality associated with SCC.2 Epidermal growth factor receptor (EGFR) is overexpressed in a large percentage of SCC. Several therapeutic trials using EGFR blockade (with agents such as lapatinib, erlotinib, or panitumumab) to treat high-risk or metastatic SCCs are ongoing.3 Cetuximab, a chimeric IgG1 monoclonal antibody against EGFR, has been considered and used in the treatment of SCC; however, formal trials have not been performed, and good data are lacking.4 The most common form of mutant EGFR, called EGFRvIII, has been described in several cancers, including head and neck cancer. It has been shown that EGFRvIII contributes to enhanced growth of SCC and resistance to EGFR inhibitor drugs.5 The aim of this study was the assessment of wild-type EGFR (wtEGFR) and EGFRvIII expression in skin SCC and its correlation with tumor biology.

Cutaneous pseudolymphoma: An unusual presentation of a deep subcutaneous thigh mass

Cutaneous pseudolymphoma is considered to be a benign (reactive) cutaneous lymphoid infiltrate; the term designates reactive diseases of the skin that histologically mimic cutaneous lymphoma. We report a case in which a 63-year-old female presented with a 5-month history of a progressive skin eruption and an enlarging subcutaneous mass following a presumed insect bite. Excisional biopsy showed this to be a pseudolymphoma extending from the dermis into the subcutaneous tissue. A number of pathological features that distinguish pseudolymphoma from cutaneous lymphoma, including histology, immunophenotype, and immunogenotype, are reviewed. The case herein challenges previous beliefs that pseudolymphoma is confined to cutaneous involvement and indicates that the process can involve deeper tissues. The final criterion for distinguishing benign from reactive processes is biological behavior. Since the depth of invasion in cutaneous pseudolymphoma has not previously been appreciated, the patient will need to be carefully examined periodically until the biological behavior of the process has been determined.