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OBJECTIVE To evaluate the presence of human papillomavirus (HPV) infection, the methylation status in the promoter region of thrombospondin‐1 (TSP‐1), RAS association domain family 1A (RASSF1‐A) and p16 genes, and the expression of TSP‐1, CD31, p16 and p53 proteins in patients diagnosed with penile cancer, and the possible associations between these variables and clinical and pathological features. PATIENTS AND METHODS HPV types, gene promoter hypermethylation and protein expression were analysed by reverse line blot, methylation‐specific polymerase chain reaction, and immunohistochemistry, respectively, in 24 penile squamous cell carcinomas. RESULTS HPV infection was detected in 11 of 24 cases (46%), and TSP‐1, RASSF1‐A and p16 genes were hypermethylated in 46%, 42% and 38% of the tumours, respectively. TSP‐1 hypermethylation was associated with unfavourable histological grade (grade 3; P = 0.033), vascular invasion (P = 0.023), weak expression of TSP‐1 protein (P = 0.041), and shorter overall survival (P = 0.04). TSP‐1 expression was not associated with microvessel density. However, RASSF1‐A hypermethylation was more frequent in T1 tumours (P = 0.01), and p16 hypermethylation was not associated with any of the tested variables except for absence of p16 expression (P = 0.022). CONCLUSION In summary, the epigenetic inactivation of TSP‐1 and RASSF1‐A genes is associated with pathological variables and seems to be of prognostic significance in penile cancer.

Squamous cell carcinoma (SCC) of the vulva is a heterogeneous disease, associated or not with vulvar lichen sclerosus (LS). The precursor role of LS in vulvar cancer is unclear. We studied the epigenetic alterations of RASSF1A, RASSF2A, p16, TSP-1 and MGMT genes in vulvar SCCs, LS associated with SCC, isolated LS and normal vulvar skin. Gene hypermethylation and human papillomavirus presence were evaluated by methylation-specific PCR and PCR/reverse line blot, respectively. High-risk human papillomavirus types were present in 16.7% of the patients with vulvar SCC. There were increasing percentages of hypermethylation of genes from isolated LS to LS associated with vulvar SCC and vulvar SCC. The genes were hypermethylated more frequently in vulvar SCC associated with LS than in those not associated with LS, MGMT and RASSF2A being unmethylated in LS not associated with vulvar SCC. TSP-1 hypermethylation was related to recurrence in patients with vulvar cancer. Conclusions are as follows: (i) the epigenetic inactivation of genes is a common event in vulvar SCC and is also present in adjacent lesions, implying a possible precursor role for these alterations; (ii) MGMT and RASSF2A hypermethylation are present exclusively in vulvar SCC and LS associated with SCC, and absent from isolated LS; and (iii) TSP-1 hypermethylation is a bad prognosis factor in vulvar SCC.Vulvar cancer (VC) accounts for 3-5% of all female genital cancers and is more frequent in women older than 75 years. Squamous cell carcinoma (SCC) is the most common type of VC and has been divided into two groups on the basis of the presence or absence of the human papillomavirus (HPV), which leads to different models of progression.2 It is well known that there are, on one hand, HPV-associated VCs of the warty or basaloid type and, on the other, keratinizing SCC, most of which are not HPV related. First, SCC associated with HPV, mostly HPV16, is the least frequent, accounting for one third of vulvar SCC. It is diagnosed at young ages and is associated with other types of cancer, such as vaginal and anal carcinoma. It shares risk factors with cervical cancer (multiple sexual partners, previous history of smoking and HPV presence and typical pathological features with warty or basaloid subtypes). The precursor lesion is of the classic vulvar intraepithelial neoplasia (VIN) type, and 4% of VIN have a risk of malignancy and frequently relapse spontaneously. 4 On the other hand, SCC that is not associated with HPV is more frequent (66% of cases), typical of older ages and more frequently associated with lichen sclerosus (LS) or squamous cell hyperplasia. 4,5 The exact role of LS in pathogenesis of VC is not yet known, but the risk of developing vulvar SCC approaches 5% in women with these lesions.5 SCC is of the keratinizing type and is preceded by differentiated VIN, which is characterized by atypical basal keratinocytes with normal maturation. These precursor lesions are rarely diagnosed, their grade of malignancy is high and they exhibit immunohistochemical ...

We describe an unusual fusocellular gonadal stromal tumour with a benign behaviour in the left testis from a 16-year-old man. The neoplasm consisted of a non-encapsulated proliferation of irregularly arranged, fusiform cell bundles in fibrous connective tissue. The tumour cells contained a slightly infolded nucleus, some dilated rough endoplasmic reticulum cisternae, abundant filament bundles which connected to subplasmalemmal electron-dense bodies, pinocytotic vesicles and a discontinuous basal lamina. The intercellular spaces were narrow and the tumour cells were joined by desmosomes. These cells were immunoreactive for muscle actin, alpha-actinin and vimentin. Focal immunostaining for collagen type IV was observed around the cells. No immunoreactivity for keratins, desmin S-100 protein or XIIIa factor was found. The findings suggest that the tumour arose from the peritubular myoid cells.

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