Phosphatase and tensin homologue (PTEN) is a tumour suppressor gene implicated in tumorigenesis of melanoma, with distinct cytoplasmic and nuclear functions. Cytoplasmic PTEN negatively regulates the PI3K/AKT/mTOR signalling pathway, while nuclear PTEN works as a tumour suppressor. Clinical data suggest that the loss of PTEN function in melanoma is associated with aggressive tumour behaviour. We performed a comprehensive analysis of PTEN in 112 primary cutaneous melanomas including immunohistochemical (IHC), fluorescent in situ hybridization (FISH), next-generation sequencing (NGS), and epigenetic analysis. The goal of our study was to: (a) correlate PTEN expression with selected clinico-pathological variables, and assess its prognostic significance; (b) correlate molecular aberrations with PTEN expression to consider the utility of immunohistochemical analysis of PTEN protein expression for screening PTEN genetic alterations; (c) review the literature and evaluate the PTEN expression level in melanoma with respect to possible therapeutic targeting. Our results showed that PTEN molecular alterations were present in 4/20 (20 %) cases with a loss of expression, 3/11 (27 %) cases with clonal-like expression, and 1/81 (1 %) cases with positive PTEN expression. No PTEN promoter methylation was found in any of the cases. Even though the value of our observation is limited by the low number of cases fully evaluated by IHC (112 cases), FISH (19 cases) and NGS (30 cases), our data suggest that IHC is not an appropriate method for the screening of PTEN genetic alterations. Our survival analysis suggests that patients with positive cytoplasmic PTEN expression show better disease-free survival (P < 0.05).
Endometrial carcinoma (ECa) is one of the most common neoplasia of the female genital tract. The phosphatase and tensin (PTEN) homolog is the most frequently mutated tumor suppressor gene in endometrial carcinoma. PTEN encodes a phosphatase, a key regulatory enzyme involved in a signal transduction pathway that regulates cell growth, migration and apoptosis. The study evaluates an association between the morphological appearance of endometrial hyperplasia and ECa, and the presence of PTEN variations, PTEN protein level and intracellular localization. A total of 67 archived formalin-fixed and paraffin-embedded human biopsy tissue specimens with normal proliferative and secretory endometrium, endometrial hyperplasia without atypia and endometrial atypical hyperplasia, endometrioid the grade G1 and G3 and serous subtype of ECa were evaluated by sequencing for the presence of mutations in coding regions of PTEN gene of endometrial epithelial cells. The PTEN gene expression and intercellular localization of PTEN protein were evaluated immunohistochemically by immunoreactive score (IRS). PTEN mutation spectrum in endometrial carcinoma was identified for Slovak population. Twenty-eight non-silent mutations were identified in PTEN, twelve of them being novel, not annotated in Catalogue of Somatic Mutations in Cancer. Higher frequency of PTEN mutations was observed in serous carcinoma compared to global average. No correlation was observed between samples IRS, PTEN cellular localization and identified mutations. PTEN sequencing can be beneficial for patients considering prognosis of disease and sensitivity to treatment.