Risk Of Neoplastic Transformation Research Articles

Gastric Polyps in Familial Adenomatous Polyposis Portuguese Patients: The First Western Cohort with Asian Features

Introduction: Chronic atrophic gastritis may contribute to gastric polyps (GP) phenotype in familial adenomatous polyposis (FAP). Considering the high prevalence of Helicobacter pylori (HP) infection in Portugal, we aim to characterize GP in a series of Portuguese patients. Methods: In a retrospectively selected series of 53 FAP patients, clinical data and histopathological features of GP and background gastric mucosa were studied. SPSS (27.0) was used for statistical analysis. Results: Thirteen patients (24.5%) developed fundic gland polyps (FGP), seven (13.2%) gastric adenomas (GA), and ten (18.9%) both FGP and GA. Out of 100 GP, four were hyperplastic polyps, 58 FGP (24 with dysplasia), 35 intestinal-type GA (intGA), and three foveolar-type GA (fovGA). IntGA were larger (60% >7 mm, p = 0.03), occurred predominantly in the distal stomach (66.7%, p = 0.024), in patients harboring gastric intestinal metaplasia (IM) (86.7%, p < 0.001), and duodenal adenomas (86.7%, p < 0.001). Conclusion: This is the first Western series showing high prevalence of intGA in FAP patients, comparable to Asian cohorts. HP infection and chronic atrophic gastritis/intestinal metaplasia are likely responsible for this difference, with risk of neoplastic transformation and management implications. Biopsy/excision of GP >7 mm in the distal stomach and in patients harboring gastric intestinal metaplasia/duodenal adenomas should be considered.

Peculiarities of intrauterine pathological processes in women of the postmenopauseal period

Aim of the research is studying the pecularities of the endometrium pathological processes in postmenopausal women on the basis of the hysteroscopy data evaluation, as well as conduction of histopathological and immunochemical studies.&#x0D; Materials and methods. To study the pecularities of intrauterine pathological processes, 100 postmenopausal women were selected and studied. All women underwent hysteroscopy with separate diagnostic scraping of the uterine cavity. Also, 10 samples of glandular-fibrous endometrial polyps (GFEP) in women of reproductive age and 9 samples of such pathology in the postmenopausal period were studied by immunohistochemical method, using 6 primary specific monoclonal antibodies.&#x0D; Results. The results showed that in 64 (64 %) postmenopausal women pathological changes of the endometrium were presented with GFEP, and in 2 patients (2 %) endometrial adenocarcinoma was found. It was also determined that the nuclei of epithelial and stromal cells of GFEP in postmenopausal women are characterized by lower expression of estrogen and progesterone receptors, compared with women with such formations in the reproductive age. In addition, it was found that in postmenopausal women the expression of the apoptosis inhibitor bcl-2 and aromatase P450 in the epithelial and stromal cells of GFEP was more expressed, and the expression of the Bах antigen, on the contrary, was significantly lower than in women of reproductive age.&#x0D; Conclusions. Fundamental molecular-biological differences of GFEP in postmenopausal women compared with women of reproductive age were revealed. It was found that in postmenopausal women there is a significantly lower dependence of such polyps on the effects of estrogen and progesterone. In addition, the data indicate an increased risk of neoplastic transformation in such women.

Risk factors and clinical correlates of neoplastic transformation in gastric hyperplastic polyps in Chinese patients

Gastric hyperplastic polyps (GHPs) have a potential risk of neoplastic transformation, but the responsible mechanisms have not yet been established. We conducted a study involving 55 patients (33 female) who had undergone endoscopic or surgical resection of GHPs. We compared 16 patients who had GHPs showing neoplastic transformation with 39 patients who had non-neoplastic GHPs. We analyzed differences in serology, gastroscopic manifestations and pathology between the two groups in order to establish risk factors that may be associated with neoplastic transformation. The mean age of the cohort was 61.73 ± 9.024 years. The prevalence of positive serum gastric parietal cell antibody (PCA) was 61.8%. 30 of the GHPs with neoplastic formation had a “strawberry-like” appearance with erosions of polyps (P = 0.000). A history of anaemia was a risk factor for GHPs which demonstrated neoplastic transformation (odds ratio [OR], 3.729; 95% confidence interval [CI], 1.099–12.649; P = 0.035). Although the differences were not significant, our data showed higher prevalences of positive serum PCA (P = 0.057), hypergastrinemia (P = 0.062) and female gender (P = 0.146) in the GHP patients who had neoplastic transformation. Multiple polyps in the corpus (P = 0.024) occurred more frequently in serum PCA positive patients. Hypergastrinemia occurred more frequently in Helicobacter pylori negative patients and of these 20/22 patients had a positive PCA (P = 0.007). GHPs are associated with autoimmune metaplastic atrophic gastritis (AMAG). AMAG is probably one of the risk factors for GHPs to undergo neoplastic transformation.

Application possibilities of biguanides for fibrocystic breast disease in women of reproductive age

Hypothesis/aims of study. The ongoing global problem of health care and medical science is an associated increase in the frequency of endocrine and metabolic diseases and cancer, including in women of childbearing age. Thus, the frequency of diabetes in the population has been growing rapidly for many years. Similar trends were observed in the dynamics of the frequency of cancer pathology, especially of breast cancer, which is one of the leading places in the structure of the cancer incidence in the female population. It is known that diabetes and related insulin resistance have a very negative effect on the female reproductive function, leading to hyperplastic processes of the mammary glands. The least studied problem so far is understanding the mechanisms of development, timely diagnosis, prevention, and treatment of fibrocystic mastopathy, the proliferative forms of which underlie malignant tumors, while its atypical variations are regarded as a precancerous condition. It is likely that the pathogenesis of hyperplastic processes in the mammary gland and the risk of neoplastic transformation in disorders of carbohydrate metabolism may have special factors. The actual problem is the development of a method for pathogenetically substantiated correction of fibrocystic breast disease. This is essential for the development of pharmacological strategies for secondary prevention of breast cancer and, in this regard, it is of great interest to study application possibilities of biguanides. The purpose of the present study was to conduct a comparative assessment of the effectiveness of metformin therapy in fibrocystic mastopathy patients with and without insulin resistance.&#x0D; Study design, materials, and methods. The study involved 120 women, aged 18 to 40 years inclusive, with clinical and / or ultrasound signs of fibrocystic breast disease. According to the results of calculating HOMA index, patients were divided into two groups: the first group comprised 66 patients with insulin resistance (HOMA &gt; 2.5) and the second group consisted of 54 patients with no insulin resistance (HOMA &lt; 2.5). Assessment of mastalgia was performed using the Visual Analogue Scale. Breast ultrasound examination was performed on days 5 to 7 of the menstrual cycle. For the purpose of quantitative image analysis of the breast parenchyma, the following parameters were evaluated: a) thickness of the parenchyma (fibroglandular zone); b) diameter of the milk ducts; c) echogenicity. All patients received metformin at a dose of 1500 mg per day. Dynamic control of the clinical picture of the disease, as well as of mammographic breast parenchymal pattern, was performed after 3 and 6 months from the start of therapy.&#x0D; Results and conclusion. After 6 months of therapy, there was a decrease in the frequency of mastalgia, and significant changes in breast ultrasound picture were observed. The data obtained on the positive effect of metformin on clinical mastitis and structural changes in the mammary parenchyma in patients with mastopathy allow considering such an approach as a promising therapeutic strategy in this pathological association.

Brachial plexus schwannoma in early adolescence. Case report

Introduction: Primary tumors arising from the peripheral nerves are a rare occurrence. In 90% they are benign, although in a small percentage there is a risk of neoplastic transformation. Schwannomas and neurofibromas are the leading etiologies. They are commonly found in the neck and large nerves of limbs and arms, with a preference for regions of the elbow, wrist, and knee. The most vulnerable group of patients are people aged 20 to 50 years. The occurrence of this type of tumors in children is sporadic, especially if the tumor includes the brachial plexus. Materials and Methods: The clinical case of a neurinoma in a supraclavicular region, affecting a 12-year-old girl. After a detailed diagnosis, the tumor finally came to be a schwannoma of a brachial plexus. Discussion: Brachial plexus schwannoma is a rare find, although it should be considered in the differential diagnosis. A detailed search for signs of neurofibromatosis (von Recklinghausen's disease) should also be performed. Initial diagnostic imaging of cervical mass includes mainly MRI, thanks to which the surgeon can suspend the tumor of nervous origin, assess the vicinity of important nerves, vessels, and cervical spinal cord, as well as qualify for the surgery. Surgical treatment should be carried out after assessing the benefits and risks associated with the procedure, including irreversible damage to the brachial plexus. To maintain safety during the operation, the use of microsurgical instruments, microscopes or endoscopes should be considered by an experienced surgeon. Preserving nerve continuity is the essential goal of the treatment, especially in young, and active patients. Finally, the long-term observation is necessary for the assessment of potential tumor neoplastic transformation, nerve function of the brachial plexus and possible symptoms of neurofibromatosis. Keywords: Brachial plexus tumor; Schwannoma in early adolescence; Neurofibromatosis; Supraclavicular swelling

Squamous cell carcinoma in the anophthalmic socket: a series of four cases with HPV-16 profiling

PurposeTo present the clinical and histological features of squamous cell carcinoma (SCC) in the anophthalmic socket in four adult patients, and to determine the presence of human papillomavirus infection (HPV).MethodsRetrospective...

Akt Protein Kinase, miR-200/miR-182 Expression and Epithelial-Mesenchymal Transition Proteins in Hibernating Ground Squirrels.

Hibernating 13-lined ground squirrels (Ictidomys tridecemlineatus; TLGS) rank among the most brain hypoperfusion-tolerant mammals known. Herein we provide some evidence of cycling between an epithelial phenotype and a hybrid epithelial/mesenchymal (E/M) phenotype (partial EMT) within the brains of TLGS during each bout of hibernation torpor. During hibernation torpor, expression of the epithelial marker E-cadherin (E-CDH) was reduced, while expression of the well-known mesenchymal markers vimentin and Sox2 were increased. P-cadherin (P-CDH), which has recently been proposed as a marker of intermediate/partial EMT, also increased during torpor, suggesting that a partial EMT may be taking place during hibernation torpor. Members of the miR-200 family and miR-182 cluster and Akt isoforms (Akt1, Akt2), well-known EMT regulators, were also differentially regulated in the TLGS brain during hibernation bouts. Using SHSY5Y cells, we also demonstrate that the Akt1/Akt2 ratio determined the expression levels of miR-200/miR-182 miRNA family members, and that these miRNAs controlled the expression of EMT-related proteins. Accordingly, we propose that such cell state transitions (EMT/MET) may be one of the mechanisms underlying the extraordinary ischemic tolerance of the TLGS brain during hibernation bouts; hibernator brain cells appear to enter reversible states that confer the stress survival characteristics of cancer cells without the risk of neoplastic transformation.

Small extracellular vesicles secreted from senescent cells promote cancer cell proliferation through EphA2

Cellular senescence prevents the proliferation of cells at risk for neoplastic transformation. However, the altered secretome of senescent cells can promote the growth of the surrounding cancer cells. Although extracellular vesicles (EVs) have emerged as new players in intercellular communication, their role in the function of senescent cell secretome has been largely unexplored. Here, we show that exosome-like small EVs (sEVs) are important mediators of the pro-tumorigenic function of senescent cells. sEV-associated EphA2 secreted from senescent cells binds to ephrin-A1, that is, highly expressed in several types of cancer cells and promotes cell proliferation through EphA2/ephrin-A1 reverse signalling. sEV sorting of EphA2 is increased in senescent cells because of its enhanced phosphorylation resulting from oxidative inactivation of PTP1B phosphatase. Our results demonstrate a novel mechanism of reactive oxygen species (ROS)-regulated cargo sorting into sEVs, which is critical for the potentially deleterious growth-promoting effect of the senescent cell secretome.

Порівняльна характеристика генетичної стабільності культур клітин жирової тканини та кісткового мозку щурів на ранніх пасажах

From literary sources, we received a number of controversial data regarding the risks of neoplastic transformation of stem cells in vitro. Inasmuch as today bone marrow has been sufficiently studied as a source of adult donor stem cells, and adipose tissue is an alternative source for obtaining cell material (from which it may be obtained using less invasive methods and in much greater quantity), determination of genetic stability of these particular cell cultures currently is the most relevant issue. Comparison of genetic stability of rat bone marrow and adipose cell cultures from the first to the sixth passages. Materials and methods: 3 non-linear 4 months old male rats and 9 non-linear 12 days old infant rats were used in the experiment. Adipose cell culture was obtained from subcutaneous fat using the standardized method in our own modification. Bone marrow cell culture was obtained from the rat femurs, tibiae, and humeri using the standardized method. Obtained cell mass was cultivated in a standard culture medium in a СО2 incubator at 37 ºС and with 5% СО2 concentration. Cytogenetic analysis was carried out on 30 metaphase plates from each passage. Cells from the first to the sixth passage we used in the research. A modification of the standard cytogenetic method was used to obtain chromosome preparations. In the preparations prepared in an aforementioned way, numerical chromosome abnormalities, like aneuploidy, polyploidy, were determined, as well as the number of binucleate cells, micronucleus cells, mitotic and apoptotic indexes. Here, we provide the comparison of genetic stability indicators for rat bone marrow and adipose cell cultures throughout the in vitro cultivation thereof. Changes in the genetic apparatus were identified in both bone marrow and adipose tissue cell cultures. Karyotype analysis of rat bone marrow and adipose cell cultures showed that, given the conditions that we used for the cultivation, the number of aneuploidies and polyploidies varies from one passage to another; however it does not go beyond the limits of spontaneous mutagenesis typical for mammals. Based on the results of cytogenetic evaluation of the culture, it was determined that the number of cells with micronuclei and the binucleate cell remains within the normal range from the first to the sixth passages. The number of cells with aneuploidy and micronuclei in adipose cell culture on all passages was lower than in bone marrow cell culture; this indicates its higher genetic stability in terms of these indicators. The highest mitotic index was determined on the first passage with its following decrease throughout the cultivation in inverse proportion to apoptotic index. The obtained data on the genetic stability of both adipose and bone marrow cell cultures are within normal range typical for mammals in terms of all studied indicators. This allows for the following studies relating to the transplantation with minimal risk of neoplastic transformation of the said cultures.

Cellular Senescence and Lung Function during Aging. Yin and Yang.

Cellular senescence is a cell fate decision and stress response that entails a permanent arrest of cell proliferation coupled to a complex secretory phenotype. Senescent cells increase in number with age in most, if not all, mammalian tissues, including the airways and lungs. They also increase at greater than expected numbers, compared with age-matched controls, at sites of age-related pathologies such as chronic obstructive pulmonary disorder and emphysema. The senescence response is a double-edged sword. The proliferative arrest suppresses the development of cancer by preventing the propagation of stressed or damaged cells that are at risk for neoplastic transformation. However, this arrest can also curtail the proliferation of stem or progenitor cells and thus hamper tissue repair and regeneration. Similarly, the secretory phenotype can promote wound healing by transiently providing growth factors and the initial inflammatory stimulus that is required for tissue repair. However, when chronically present, the secretory phenotype of senescent cells can drive pathological inflammation, which contributes to a host of age-related pathologies, including cancer. There are now transgenes and prototype small molecules that can clear senescent cells, at least in mouse models, and thus improve health span and median life span. The next challenge will be to develop interventions and supplements that can abrogate the deleterious effects of senescent cells while preserving their beneficial effects.

Genomic imbalance in endometrial hyperplasia and cancer

Endometrial cancer belongs to the most frequently diagnosed malignant neoplasms of female genital organs, and its incidence is steadily growing. For the timebeing, no chromosomal aberrations have been determined unequivocally, which would be specific for the particular stages of endometrial hyperplasia and neoplastic transformation development. The goal of the undertaken studies was an identification of the earliest and specific genetic changes, which could be attributed to an increased risk of neoplastic transformation in a group of patients with endometrial hyperplasia plus the characteristics of genetic changes associated with the mature form of neoplasm. The study involved forty-four (44) patients, including five (5) histopathologically unconfirmed hyperplasia, twenty-six (26) with histopathologically confirmed endometrial hyperplasia and thirteen (13) with diagnosed endometrial cancer. The applied aCGH (array Comparative Genomic Hybridisation) method enabled selection of a few chromosomal regions which indicated a higher incidence of chromosomal rearrangements than in the control group. The study included also an evaluation of the frequency of mutations of the genes specific for neoplastic transformation development, the genes at chromosomal loci, which most frequently presented with genomic imbalance. In cases without hyperplasia, changes were diagnosed, described as CNVs (Copy Number Variations), which occurred with varying prevalence in the genome of the population of healthy subjects. Significant genomic imbalance was identified in 26 (100%) patients with diagnosed hyperplasia and in 11 (84.6%) of the patients with diagnosed endometrial cancer. Also other, till now unreported changes were found, localised at characteristic regions of the genome.

Phenotype switching through epigenetic conversion.

Different cell types have been suggested as candidates for use in regenerative medicine. Embryonic pluripotent stem cells can give rise to all cells of the body and possess unlimited self-renewal potential. However, they are unstable, difficult to control and have a risk of neoplastic transformation. Adult stem cells are safe but have limited proliferation and differentiation abilities and are usually not within easy access. In recent years, induced pluripotent stem (iPS) cells have become a new promising tool in regenerative medicine. However, the use of transgene vectors, commonly required for the induction of iPS cells, seriously limits their use in therapy. The same problem arising from the use of retroviruses is associated with the use of cells obtained through transdifferentiation. Developing knowledge of the mechanisms controlling epigenetic regulation of cell fate has boosted the use of epigenetic modifiers that drive cells into a 'highly permissive' state. We recently set up a new strategy for the conversion of an adult mature cell into another cell type. We increased cell plasticity using 5-aza-cytidine and took advantage of a brief window of epigenetic instability to redirect cells to a different lineage. This approach is termed 'epigenetic conversion'. It is a simple, direct and safe way to obtain both cells for therapy avoiding gene transfection and a stable pluripotent state.

Senescence-associated release of transmembrane proteins involves proteolytic processing by ADAM17 and microvesicle shedding.

Cellular senescence, a state of persistent cell cycle arrest, has emerged as a potent tumor suppressor mechanism by restricting proliferation of cells at risk for neoplastic transformation. Senescent cells secrete various growth factors, cytokines, and other proteins that can either elicit the clearance of tumor cells or potentially promote tumor progression. In addition, this senescence-associated secretory phenotype (SASP) includes various factors that are synthesized as transmembrane precursors and subsequently converted into their soluble counterparts. Despite the importance of the SASP to tumor biology, it is virtually unknown how transmembrane proteins are released from senescent cancer cells. Here we show in different models of senescence that the metalloprotease A disintegrin and metalloproteinase 17 (ADAM17) is activated and releases the epidermal growth factor receptor ligand amphiregulin and tumor necrosis factor receptor I (TNFRI) from the surface of senescent cells by ectodomain shedding. ADAM17 activation involves phosphorylation of its cytoplasmic tail by mitogen-activated protein kinase (MAPK) p38. Interestingly, unlike amphiregulin and TNFRI, full-length intercellular adhesion molecule 1 (ICAM1) is released from senescent cells by microvesicles independently of ADAM17. Thus, our results suggest that transmembrane proteins can be released by two distinct mechanisms and point to a crucial role for ADAM17 in shaping the secretory profile of senescent cells.

76: ADAM17 is activated upon cellular senescence and contributes to the secretory profile of senescent cells by ectodomain shedding

Senescence is the irreversible growth arrest following cellular stressors such as DNA damage. It has become increasingly apparent that senescence represents a crucial tumor suppressor mechanism restricting the proliferation of cells at risk for neoplastic transformation. By secreting numerous cytokines, growth factors as well as proteases – a phenomenon that has been termed Senescence – Associated Secretory Phenotype (SASP) – senescent cells generate a strong proinflammatory environment likely promoting the development of chronic inflammatory diseases and – paradoxically – cancer. The supernatant of senescent cells contains various SASP factors, that are primarily synthesized by the cell as membrane-bound proteins and only afterwards are converted into their soluble counterpart by – as yet unknown – posttranslational means. Here, we show that upon induction of cellular senescence the metalloprotease ADAM17 is activated and releases Amphiregulin and TNFRI from the surface of human cancer cells as well as primary cells by ectodomain shedding. ADAM17 activation involves phosphorylation of its cytoplasmic tail, which is mediated by MAP kinase p38. In addition, these findings have been confirmed in primary embryonic fibroblasts derived from ADAM17 deficient mice suggesting that ADAM17-mediated shedding of SASP components is relevant across species. However, mechanisms governing the SASP are complex, since elevated levels of ICAM-1 are due to increased microparticle release rather than proteolytic ectodomain shedding.

The role of phosphoinositide 3-kinase subunits in chronic thyroiditis

BackgroundThe risk of neoplastic transformation in patients with chronic thyroiditis (Hashimoto’s thyroiditis – HT) is slightly increased. Genetic background of this observation is still unclear. PI3K isoforms are linked with inflammatory and neoplastic processes, thus they appear to be interesting subjects of a research in this respect. The aim of our study was to assess the PIK3CA, PIK3CB, PIK3CD and PIK3CG genes expression levels in HT.MethodsFollowing conventional cytological examination, 67 thyroid FNAB specimens, received from patients with HT, were quantitatively evaluated regarding PIK3CA, PIK3CB, PIK3CD and PIK3CG expression levels by real-time PCR in the ABI PRISM ®7500 Sequence Detection System.ResultsThe performed analysis has revealed significantly higher expression levels (RQ) of PIK3CD, PIK3CG and PIK3CA genes in comparison with PIK3CB gene (p<0.05) and significantly higher gene expression level of PIK3CD in comparison with PIK3CA (p<0.05).ConclusionThe observed increased PIK3CD, PIK3CG genes expression in HT is probably related to lymphocyte infiltration commonly seen in this condition, however, the role of increased PIK3CA gene expression in the multi-step carcinogenesis process cannot be excluded.

Mitochondrial oxidative stress caused by Sod2 deficiency promotes cellular senescence and aging phenotypes in the skin.

Cellular senescence arrests the proliferation of mammalian cells at risk for neoplastic transformation, and is also associated with aging. However, the factors that cause cellular senescence during aging are unclear. Excessive reactive oxygen species (ROS) have been shown to cause cellular senescence in culture, and accumulated molecular damage due to mitochondrial ROS has long been thought to drive aging phenotypesin vivo. Here, we test the hypothesis that mitochondrial oxidative stress can promote cellular senescence in vivo and contribute to aging phenotypes in vivo, specifically in the skin. We show that the number of senescent cells, as well as impaired mitochondrial (complex II) activity increase in naturally aged mouse skin. Using a mouse model of genetic Sod2 deficiency, we show that failure to express this important mitochondrial anti-oxidant enzyme also impairs mitochondrial complex II activity, causes nuclear DNA damage, and induces cellular senescence but not apoptosis in the epidermis. Sod2 deficiency also reduced the number of cells and thickness of the epidermis, while increasing terminal differentiation. Our results support the idea that mitochondrial oxidative stress and cellular senescence contribute to aging skin phenotypes in vivo.

Epigenetic variability in cells of normal cytology is associated with the risk of future morphological transformation

BackgroundRecently, it has been proposed that epigenetic variation may contribute to the risk of complex genetic diseases like cancer. We aimed to demonstrate that epigenetic changes in normal cells, collected years in advance of the first signs of morphological transformation, can predict the risk of such transformation.MethodsWe analyzed DNA methylation (DNAm) profiles of over 27,000 CpGs in cytologically normal cells of the uterine cervix from 152 women in a prospective nested case-control study. We used statistics based on differential variability to identify CpGs associated with the risk of transformation and a novel statistical algorithm called EVORA (Epigenetic Variable Outliers for Risk prediction Analysis) to make predictions.ResultsWe observed many CpGs that were differentially variable between women who developed a non-invasive cervical neoplasia within 3 years of sample collection and those that remained disease-free. These CpGs exhibited heterogeneous outlier methylation profiles and overlapped strongly with CpGs undergoing age-associated DNA methylation changes in normal tissue. Using EVORA, we demonstrate that the risk of cervical neoplasia can be predicted in blind test sets (AUC = 0.66 (0.58 to 0.75)), and that assessment of DNAm variability allows more reliable identification of risk-associated CpGs than statistics based on differences in mean methylation levels. In independent data, EVORA showed high sensitivity and specificity to detect pre-invasive neoplasia and cervical cancer (AUC = 0.93 (0.86 to 1) and AUC = 1, respectively).ConclusionsWe demonstrate that the risk of neoplastic transformation can be predicted from DNA methylation profiles in the morphologically normal cell of origin of an epithelial cancer. Having profiled only 0.1% of CpGs in the human genome, studies of wider coverage are likely to yield improved predictive and diagnostic models with the accuracy needed for clinical application.Trial registrationThe ARTISTIC trial is registered with the International Standard Randomised Controlled Trial Number ISRCTN25417821.

Induction of senescence in melanoma: thinking outside the cell

Induction of senescence in melanoma: thinking outside the cell

Chemical Peels May Prevent Skin Cancers

Chemical peels are popular procedures for the rejuvenation of photoaged skin. They improve skin texture and improve dyspigmentation by controlled injury to the epidermis and dermis. Because this procedure is used on skin with a heightened risk for neoplastic transformation, its effect on nonmelanoma skin cancer formation comes into question. On the one …

Spectrum of colon polyposis and colonic neoplasia in the PTEN hamartoma tumor syndrome (PHTS).

3627 Background: PHTS consists of a group of familial disorders associated with germline mutations of the PTEN gene. Cowden syndrome is the most common phenotype. Affected patients develop a variety of tumors, including polyposis of the gastrointestinal tract. Based on current literature, PHTS is not associated with an increased risk of colon cancer; therefore, the risk of neoplastic transformation and appropriate screening intervals for PHTS-associated colon polyposis is not well characterized. This study was performed to better define the incidence and outcomes of colon polyposis in PHTS. Methods: Patients with a clinical diagnosis of PHTS at the Mayo Clinic were identified from 1980 to 2009. Only patients that met the NCCN consortium criteria for diagnosis were included. The relevant clinical information, onco-pathology data and molecular studies were retrospectively reviewed. Results: 47 patients with PHTS were identified, of which 17 (36%) had colon studies at our institution. All met criteria for Cowden disease. Of the 14 that underwent a colonoscopy, 13 (93%) were noted to have diffuse polyposis, with 9 (64%) estimated to have > 50 polyps. 15 patients had colon biopsies reviewed (median age 47 at first biopsy). The spectrum of tumors included hamartomas (n = 12), ganglioneuromas (n = 6) and tubular adenomas (n = 6). 7 (47%) patients had low-grade dysplasia (median age 50 at first detection), including 1 patient with dysplasia within hamartomatous polyps. 2 (12%) patients, age 56 and 62, had early-stage (T1N0M0, grade II and T2N0M0, grade III) left-sided colonic adenocarcinomas. Neither showed evidence of microsatellite instability. 7 (41%) patients underwent colectomy (median age 45), of which 4 had colonic dysplasia/neoplasia and 3 had symptomatic polyposis. Conclusions: This is the largest series from a single institution to examine the colonic manifestations of PHTS. Our findings suggest that germline mutations in the PTEN gene are associated with a spectrum of colonic tumors, including hamartomas, ganglioneuromas, tubular adenomas and colon cancer. Colonic dysplasia and neoplasia were more common then expected. If confirmed, colon cancer screening recommendations should be developed for patients with PHTS. No significant financial relationships to disclose.