Epidemiology, Diagnosis and Treatment Outcomes of Skin Melanoma in the Republic of Belarus

The primary incidence of skin melanoma in the Republic of Belarus over 25 years (from 1991 through 2015) has increased 3.3-fold (from 2.6 to 9.0 per 100,000 population). A higher level of urban population incidence, a large proportion of people affected at the employable age. In 2015 the proportion of prognostically unfavourable pT3-pT4 neoplasms was 38.2%. Metastatic disease was detected in 12.4% of the patients. Methodology: Material of the paper is based on the data of Belarusian Cancer Registry using the principles of data collection, monitoring and processing recommended by the IARC. Results: The proportion of stage IB neoplasms made up almost one third of the cases assigned to stage I. Of the cases assigned to stage II, the proportion of neoplasms with a high prognostic index of metastatic spread (T3b-T4b) was more than 70%. The recurrence rate is 15.1% even at melanoma invasion depth of up to 1 mm (with ulceration), while it rises to 32.4% at pT2b. The cumulative 5-year disease-specific survival of all patients in 2005 was 54.1 ± 1.5%, and in 2015 it was 64.0±2.2%. Conclusion: A strong correlation is observed between survival of patients and the extent of invasion and ulceration of the primary focus. For metastasis-free pT1a melanoma, the 5-year survival was 92.2%, for T1b – 79.9%, for pT2b – 72.5%, for pT3b – 55.1%, for pT4b – 49.1%. According to the Cancer Registry data, ulceration of the primary neoplasm is frequently observed: it amounts to 41.1% of the cases with melanoma invasion depth up to 2 mm (pT2), to 55.9% with 2-4 mm (pT3) and to 76.3% with the tumor thickness of more than 4 mm (pT4)

The opposite association of HRAS and KRAS mutations with clinical variables of bladder cancer

HRAS, KRAS and NRAS gene products belong to the superfamily of small GTPases. These proteins regulate cellular response to extracellular stimuli by means of activation of different signaling pathways. Although the role of RAS gene mutations in the pathogenesis of various human cancers has been established, the clinical significance of these molecular alterations in bladder cancer remains unclear. The aim of this study was to determine the frequency and spectrum of HRAS, KRAS and NRAS mutations, to analyze their relationships with clinicopathological variables and to determine the prognostic value of these alterations in terms of recurrence, progression and mortality, in a prospective cohort of 249 bladder cancer patients. The frequency of RAS mutations detected by the SNaPshot method, was found to be 11.2 %, of which HRAS mutations accounted for 64.3 %, KRAS, for 28.6 % and NRAS, for 7.1 %. We failed to find any correlation between all RAS mutations and pathomorphological characteristics. However, when analyzed separately, HRAS and KRAS mutations were for the first time shown to be associated with the opposite clinical parameters of bladder cancer: HRAS mutations were significantly associated with low-stage low-grade papillary tumors of a small size (р < 0.05), whereas KRAS mutations were associated with non-papillary urothelial carcinomas and the presence of metastasis (р < 0.05). Analysis of the prognostic value of molecular alterations revealed an association of KRAS mutations with decreased cancer-specific survival in both the whole group of patients and the subgroup with non-muscle invasive disease. The data obtained suggest that HRAS and KRAS gene mutations may characterize alternative pathways of bladder cancer pathogenesis: HRAS mutations indicating benign and KRAS mutations, aggressive disease course