Retinoic acid suppresses telomerase activity in HSC-1 human cutaneous squamous cell carcinoma.

BACKGROUND: Activation of telomerase is crucial for the continued growth and progression of cancer cells. In a previous study, we showed that telomerase is frequently activated in skin tumours. OBJECTIVE: Because retinoic acid (RA) plays an important role in the growth and differentiation of keratinocytes and as RA has some preventive and therapeutic effects on human skin cancers, we examined the effect of RA on the telomerase activity of HSC-1 human cutaneous squamous cell carcinoma cells. RESULTS: Treatment of HSC-1 cells with all-trans RA (ATRA) significantly suppressed their telomerase activity. The suppression of telomerase activity was obvious at day 4 and was maximal at day 5 after the start of treatment with RA. This suppression was reversible as removal of ATRA allowed the recovery of telomerase activity. The suppression of telomerase activity correlated with the decreased expression of mRNA of human telomerase catalytic subunit (hTERT), the rate-limiting determinant of enzyme activity. The production of c-myc and of Sp1 proteins, transcription factors regulating hTERT expression, was not suppressed in HSC-1 cells by ATRA, but phosphorylation of extracellular signal-regulated kinases (ERK)1/2 and of the serine/threonine kinase Akt was significantly suppressed. Phosphorylation of the epidermal growth factor receptor, which regulates hTERT expression in HSC-1 cells, was not altered by ATRA. CONCLUSIONS: These data indicate that RA is effective in inhibiting telomerase activity in HSC-1 cells. Suppression of ERK1/2 and Akt activation is presumed to be involved in the RA-induced suppression of hTERT.

Bowen's carcinoma of the scrotal skin associated with human papillomavirus type 82.

We have previously cloned human papillomavirus type 82 (HPV-82) from a vaginal intraepithelial neoplasia, but it is not known whether HPV-82 can induce a cutaneous lesion. A large erosive nodule developed on the scrotum of a 50-year-old Japanese patient. Histopathologically, the lesion was composed of two distinct parts; one part showing changes characteristic of Bowen's disease in the epidermis, and the other showing elongated rete ridges and proliferation of atypical basaloid cells in the dermis. These parts were partially connected, giving the diagnosis of Bowen's carcinoma. Immunohistochemically, HPV capsid antigen was detected only in the nuclei of a few cells on the upper part of the epidermis. HPV-82 was identified in the lesion by blot hybridization and viral DNA was demonstrated in the lesion by in situ hybridization. HPV-82 has tropism for both the skin and the genital regions.

Protean manifestations of human papillomavirus type 60 infection on the extremities.

BACKGROUND: Human papillomavirus type 60 (HPV-60) induces a ridged wart or an epidermal cyst on the sole of the foot, exhibiting identical pathological changes, with a single refractile eosinophilic intracytoplasmic inclusion body in infected cells. However, there is no information on the role of HPV-60 in the development of cutaneous lesions on other anatomical sites. OBJECTIVES: To perform the clinicopathological analysis of various cutaneous lesions of a patient in relation to HPV genotype. PATIENT: A 50-year-old male patient developed multiple papules, plaques and nodules on his hand, arm and legs. RESULTS: Clinicopathologically, the lesions were classified into three categories. A common wart on the finger showed papillomatosis and acanthosis characterized by numerous keratohyalin granules. Plane warts on the arm showed perinuclear vacuolization of the cells in the upper Malpighian layer. On the other hand, a pigmented papillomatous nodule on the finger, and the other lesions on the hands and legs exhibited similar histological features with a unique cytoplasmic eosinophilic inclusion body. All the three categorized lesions were equally positive for HPV capsid antigen by immunohistochemistry. By blot hybridization analysis for HPV sequences, it was revealed that a common wart on the finger and plane warts on the arm harboured HPV-27 and HPV-3, respectively, while all the other lesions harboured HPV-60. The histological localization of each viral DNA was confirmed in the corresponding lesions by in situ hybridization. CONCLUSIONS: HPV-60 is able to induce papular and nodular lesions on the extremities.

Nasal-type natural killer cell lymphoma preceded by benign panniculitis arising in an asymptomatic HTLV-1 carrier.

We report a case of an Epstein-Barr virus (EBV)-associated nasal-type natural killer cell lymphoma (NKCL) preceded by benign panniculitis, which arose in a 48-year-old woman with an asymptomatic human T-cell leukemia/lymphoma virus type-1 (HTLV-1) infection. A biopsy of the initial panniculitis lesion demonstrated lobular panniculitis with a germinal center composed of benign mononuclear cells with a phenotype of CD4+CD45RO+CD5sCD3+ cCD3 epsilon + T-cell intracellular antigen-1 (TIA-1)- and granzyme B-. One year after oral prednisolone therapy, the patient developed subcutaneous nodules composed of atypical lymphoid cells with a phenotype of CD4-CD45RO+CD56+sCD3-cCD3 epsilon + (TIA-1)+ and granzyme B+. In the initial panniculitis lesion, neither EBV-encoded RNA (EBER-1) nor clonal proliferation of EBV-infected cells was identified. In later lesions, however, a large number of atypical cells were positive for EBER-1, and a clonal expansion of EBV-infected cells was detected. No clonal rearrangement of T-cell receptor-alpha, -beta, or -gamma genes was found in either specimen. This patient was an asymptomatic carrier of human T-cell leukemia/lymphoma virus type-1 (HTLV-1) without clonal integration of proviral HTLV-1 in neither the peripheral blood nor the skin lesions. These observations suggest that EBV-associated NKCL occurred subsequently in the clinical course of benign panniculitis under the influence of immunosuppression caused by prednisolone treatment and HTLV-1 infection.