Expression of Cell Cycle and Apoptosis Regulatory Proteins and Telomerase in Melanocitic Lesions

To gain insight into the role and association of cell cycle and apoptosis regulatory proteins and telomerase activity in the course of progression of melanocitic lesions we have examined immunohistochemicaly, expression and the distribution of p53, bcl-2, Ki-67 and telomerase in 25 samples of common and dysplastic nevi, and 45 samples of primary invasive melanomas. Protein p53 expression was significantly increased in dysplastic as compared with common nevi and melanomas (p<0.001). Bcl-2 protein expression was significantly increased in melanomas as compared with common aquired and dysplastic nevi (p=0.001). Nevi and melanomas exhibited clear-cut differences in terms of Ki-67 expression. Telomerase expression was significantly increased in melanomas as compared with common acquired (p=0.014) and dysplastic nevi (p<0.001). Enhanced telomerase activity in association with increased bcl-2 expression in the course of melanoma progression could contribute to development and progression of melanoma

Apoptosis in Skin Cancer Development and Regression

Non-melanoma skin cancers (NMSC) are the most common malignant tumors in white population and their incidence has been increasing worldwide. Molecular events regulating cell survival, apoptosis, growth arrest as well as cell differentiation, are important contributors to the overall kinetics of benign and malignant cell growth and play a role in their development, progression and regression. Failure of these pathways can result in the loss of control over proliferation and lead to tumor development through the inactivation of tumor suppressor genes or the activation of oncogenes. Also, immunological mechanisms have been implicated in a phenomenon of tumor progression as well as spontaneous tumor regression. We have tried to summarize the main events in etiopatogenesis, development, progression and in some cases skin cancer regression. Further studies are needed to elucidate completely the details of apoptotic control in normal skin and determine factors resulting in apoptotic disbalance and disease

Breast Infiltrating Ductal Carcinoma: Analysis of Hormone, HER-2 Receptors and Ki-67 Proliferation Marker

The aim of this study was to analyse breast carcinomas with discordant receptor status, probably hormonal dependent (estrogen receptor (ER) positive, progesterone receptor (PR) negative or ER-PR+ subgroup profile) infiltrating ductal breast carcinomas not otherwise specified (IDC NOS). Specimens from 90 IDC NOS were grouped into three categories according to hormonal status: dependent (D) (ER+PR+), probably dependent (PD) (ER+PR- or ER-PR+) and non-dependent (ND) (ER-PR-); they were evaluated considering some established prognostic parameters in breast carcinomas. Statistically significant difference was found between tumor receptor status distribution and menopausal status (p= 0.0235), age of the patients (p=0.000467), histological grade (p=0.000003), vascular invasion (p=0.006), HER-2 status (p=0.0039) and Ki-67 proliferation rate (p=0.000311). D tumors were found exclusively in post-menopausal patients (average age 68.9 years), most of which had intermediate (II) grade, without vascular invasion, with HER-2 status score predominantly 0 or 1+ and lower Ki-67 proliferation rate. PD tumors were found predominantly in younger post-menopausal patients (average age 57.5 years), with vascular invasion found in 23% of the cases. ND tumors mostly had higher histological grade, showed the highest percentage of the Ki-67 positive tumor cells and vascular invasion in 30% of the cases. We conclude that the patients with PD breast carcinomas were younger post-menopausal women with the tumors moderately differentiated, HER-2 score 0 or 1+ and with lower Ki-67 proliferation rate

Tibial Stress Fracture Simulate Osteomyelitic Foci in the Course of Chronic Recurrent Multifocal Osteomyelitis

Chronic recurrent multifocal osteomyelitis (CRMO) is an extremely rare and most severe form of chronic nonbacterial osteomyelitis of unknown etiology. Here we present the first case of a six-year-old girl in which was observed that the stress fracture mimic osteomyelitic foci in the course of CRMO

Skin melanoma heterogeneity and its molecular aspects

U Hrvatskoj je zabilježen 2,7 postotni godišnji porast mortaliteta od melanoma kože. U više studija otkriveno je da osobe koje razviju melanom na abdomenu imaju znatno veći broj madeža od osoba koje razviju melanom na glavi ili vratu. Suprotno tome, melanomi na glavi i vratu povezani su sa solarnom keratozom, ali vrlo slabo s brojem madeža. Otkrivena je povezanost podtipa lentigo maligna melanoma sa značajnim izlaganjem suncu, ali nikakve konstantne korelacije nisu pronađene kod drugih histoloških podtipova. Nova molekularno genetska istraživanja snažno podržavaju koncept da su melanomi nastali na centralnim dijelovima tijela kod mlađih osoba s velikim brojem melanocitnih madeža biološki različiti od melanoma nastalih kumulativnim djelovanjem na suncem oštećenoj koži starijih ljudi i da su madeži i melanomi istog puta nastanka vođeni istim genetskim promjenama. Epidemiološke stručne analize brzo su utvrdile da visok stupanj izloženosti suncu znači veći broj madeža u ranom djetinjstvu. Višestruka istraživanja pokazala su da BRAF-mutirajući melanomi najčešće spadaju u superficijalno-šireći podtip i pojavljuju se na koži koja je povremeno bila izložena suncu kao i da češće metastasiziraju u regionalne limfne čvorove nego melanomi bez BRAF mutacija. KIT-mutiranimelanomi se pojavljuju u koži, na noktima, na mukozi ili na koži koja je oštećena suncem te najčešće isključuju BRAF mutaciju. Melanomi s ovom mutacijom vrlo često imaju in situ komponente koje su slabo ograničene, što je rezultat pojačane lateralne mobilnosti neoplastičnih melanocita nakon aktivacije SCF KIT puta.Croatia has recorded a 2.7 percent annual increase in melanoma of the skin mortality. Several studies have found that people who develop melanoma on the abdomen carry a significantly higher number of nevi than people who develop melanoma on the head or neck. In contrast, melanoma on the head and neck is associated with solar keratosis, but not with the number of nevi. The correlation was found between lentigo maligna melanoma incidence and exposure to the sun. No similar correlation was found in other histological subtypes of melanoma. New molecular genetic studies support the concept that melanomas arising in the central parts of the body of young people carring multiple nevi are biologically different from melanoma caused by cumulative action of the sun-damaged skin in older patients. Epidemiological expert analysis quickly determined that a high degree of exposure to the sun means a larger number of moles in early childhood. Multiple studies have shown that BRAF-mutant melanoma most often fall into the superficial-spreading subtype and appear on skin that has occasionally been exposed to the sun and that they more often methasize to regional lymph nodes than melanomas without the BRAF mutation. KITmutated melanoma appear in the skin, the nails, the mucosa or the skin, which is damaged by the sun and usually exclude BRAF mutations. Melanomas with this mutation often carry na poorly delimited in situ components as a result of enhanced lateral mobility of neoplastic melanocytes after the SCF KIT pathway activation

Atypical Spitz Tumor of Uncertain Biologic Potential with Inopportune Localization in 7- year-old Boy

Letter to the editor No abstract available</p

Mometasone Furoate and Nasal Vascularisation in Allergic Patients

Angiogenesis, the growth and proliferation of new blood vessels, is important in a variety of pathophysiological processes. However the role of angiogenesis in allergic rhinitis has not been well studied. Hence, the aim of this study was to compare the vascularisation of the nasal mucous membrane of non-allergic, non-treated allergic and allergic patients treated with mometasone furoate. A small piece of the nasal mucous membrane was taken from the frontal pole of the lower nasal shell from 90 patients. The patients were divided in three groups, each containing 30 patients. First group of patients (GP1) had a negative inhalatory allergen test, patients in second group (GP2) had positive test but were not under treatment and the third group of patients (GP3) had positive results with the same test and were treated with mometasone furoate for 15 days before analysis. Immunhistochemical staining with anti-CD31 and VEGF-C was performed. Vascular phase was determined by using length density. Differences in expression of CD31 and VEGF-C were compared using one-way ANOVA and Tukey HSD post-hoc tests. Significantly lower values of CD31 and VEGF-C expression were observed in GP1 in compare with GP2 and GP3 (p<0.001, p=0.013, respectively). In GP3 the microvessel density was significantly lower than in GP2 (p<0.001), but higher than in GP1. Our results demonstrated that 15-day treatment with mometasone furoate results in a significant reduction of the density of vascular parameters in allergic patients

Cell Apoptosis as Assessed by M30 Expression in Keratoacanthoma and Squamous Cell Carcinoma

Involution displayed by keratoacanthoma (KA) represents an important difference between KA and squamous cell carcinoma (SCC). It has been suggested that apoptosis plays a part in process of involution of KA. Altogether 150 specimens were included in this study, 30 cases of each; normal skin (NS), proliferative (pKA) and regressing keratoacanthoma (rKA), well differentiated (wdSCC) and poorly differentiated (pdSCC) squamous cell carcinoma. All samples were examined immunohistochemicaly for expression of M30 protein. A significantly lower number of M30 positive cells has been detected in NS as compared to skin tumors examined (p<0.001), except for rKA (p=0.057). The highest percentage of M30 positive cells was detected in pdSCC (p<0.001) as compared with all other examined groups. Keratinocytes of normal and changed epidermis expressing higher levels of M30 protein were predominately found in sun-exposed areas (c 2=14.93; p=0.060). There was an increasing trend of M30 protein expression with increasing age of the patient in NS and skin tumors examined. Majority of skin tumors with higher percentage of M30 positive cells tended to display higher Ki-67 expression. M30 expression was highly correlated with bak (r=0.811; p=0.048) and granzyme B expression in rKA (r=0.733; p=0.015). Cell apoptosis as assessed by M30 expression is, generally, increased in examined skin tumors and related to cell proliferation. Cell apoptosis mediated by bak and granzyme B expression could contribute to KA regression