Estudio inmunohistoquímico del carcinoma epidermoide de labio

Objetivos: Determinar la sobreexpresión de las proteínas cerb- B2, p53, bcl-2, Ki67 y CD44varV6 y establecer su valor pronóstico en el carcinoma epidermoide de labio. Diseño del estudio: Estudio inmunohistoquímico de las proteínas p53, c-erb-B2, bcl-2, ki67 y CD44varV6 en 79 carcinomas epidermoides de labio diagnosticados y tratados a lo largo de un periodo de 20 años. Los datos obtenidos fueron sometidos a análisis estadístico uni y multivariante. Resultados: La inmunotinción fue positiva en el 75% de los casos para la proteína c-erb-B2, en el 70,6% para la proteína p 53, en el 3,8% para la proteína bcl-2 y en el 89,9% para la molécula de adhesión cd44varV6. La expresión proteica de ki67 osciló entre un mínimo de 0% y un máximo de 6,29%. Los factores inmunohistoquímicos analizados no presentaron valor pronóstico en el carcinoma epidermoide de labio, y solamente los pacientes afectados por este tipo de tumores que expresaban la molécula de adhesión CD44varV6 se asociaron de forma significativa con una mayor supervivencia mediante el análisis de Kaplan-Meier. Conclusiones: Las técnicas inmunohistoquímicas analizadas para el estudio anatomopatológico del carcinoma epidermoide de labio no deberían realizarse rutinariamente, dado su mayor coste y su menor utilidad en la práctica clínica diaria.Objectives: To determine the expression of the c-erb-B2, p53, bcl-2, Ki67 and CD44varV6 proteins, and to establish their prognostic value in epidermoid carcinoma of the lip. Study design: Immunohistochemical study of the c-erb-B2, p53, bcl-2, Ki67 and CD44varV6 proteins in 79 epidermoid carcinomas of the lip, diagnosed and treated over a period of 20 years. The data obtained were subjected to uni- and multi-variate statistical analyses. Results: Immunostaining was positive in 75% of cases for c-erb- B2 protein, in 70.6% for p53 protein, in 3.8% for bcl-2 protein and in 89.9% for adhesion molecule CD44varV6. Ki67 protein expression varied between a minimum of 0% and a maximum of 6.29%. Most immunohistochemical factors analyzed presented no prognostic value for epidermoid carcinoma of the lip. Only those patients affected by this type of tumor that expressed the adhesion molecule CD44varV6 were significantly associated with a greater survival calculated by means of Kaplan-Meier analysis. Conclusions: The immunohistochemical techniques analyzed for the anatomicopathological study of epidermoid carcinoma of the lip should not routinely be used due to their high cost and low utility in daily clinical practice

A Rule Based Classification Model to Predict Colon Cancer Survival

Introduction: Colon cancer is the second most common cancer in the world and fourth most common cancer in both sexes in Iran, whose % 8.12 of all cancers in the covers. Predict the outcome of cancer and basic clinical data about it is very important. Data mining techniques can be used to predict cancer outcome. In our country, data mining studies on colon cancer, not covered as lung or breast cancers. It seems can be with identify factors influencing on survival and modify them, increased survival of colon cancer patients. Then according to high rates of colon cancer and the benefits of data mining to predict survival, in this study examined factors influencing on the survival of these patients. Materials and Methods: We use a dataset with four attributes that include the records of 570 patients in which 327 Patients (57.4%) and 243 (42.6%) patients were males and females respectively. Trees Random Forest (TRF), AdaBoost (AD), RBF Network (RBFN), and Multilayer Perceptron (MLP) machine learning techniques with 10-cross fold technique were used with the proposed model for the prediction of colon cancer survival. The performance of machine learning techniques were evaluated with accuracy, precision, sensitivity, specificity, and area under ROC curve. Results: Out of 570 patients, 338 patients and 232 patients were alive and dead respectively. In this Study, at first sight it seems that among this techniques, Trees Random Forest (TRF) technique showed better results in comparison to other techniques (AD, RBFN and MLP). The accuracy, sensitivity, specificity and the area under ROC curve of TRF are 0.76, 0.808, 0.70 and 0.83, respectively. Conclusions: In this study seems that Trees Random Forest model (TRF) which is a rule based classification model was the best model with the highest level of accuracy. Therefore, this model is recommended as a useful tool for colon cancer survival prediction as well as medical decision making

The mTORC1 inhibitor everolimus prevents and treats Eμ-Myc lymphoma by restoring oncogene-induced senescence

MYC deregulation is common in human cancer. IG-MYC translocations that are modeled in EμMyc mice occur in almost all cases of Burkitt lymphoma as well as in other B-cell lymphoproliferative disorders. Deregulated expression of MYC results in increased mTOR complex 1 (mTORC1) signaling. As tumors with mTORC1 activation are sensitive to mTORC1 inhibition, we used everolimus, a potent and specific mTORC1 inhibitor, to test the requirement for mTORC1 in the initiation and maintenance of EμMyc lymphoma. Everolimus selectively cleared premalignant B cells from the bone marrow and spleen, restored a normal pattern of B-cell differentiation, and strongly protected against lymphoma development. Established EμMyc lymphoma also regressed after everolimus therapy. Therapeutic response correlated with a cellular senescence phenotype and induction of p53 activity. Therefore, mTORC1-dependent evasion of senescence is critical for cellular transformation and tumor maintenance by MYC in B lymphocytes

Novel non-invasive adjunctive techniques for early oral cancer diagnosis and oral lesions examination

Oral cancer is a potentially fatal disease with an increasing incidence and an unchanged 5-year mortality rate. Unfortunately, oral cancer is often still late diagnosed, which leads to an increase in the likelihood of functional impairment due to treatment and mortality rate. Definitive diagnosis of oral cancer must be confirmed by scalpel biopsy and histological assessment. However despite its benefits, scalpel biopsy is invasive and it is burdened by a potential morbidity. Furthermore, previous studies have suggested a high degree of intraobserver and interobserver variability regarding the histological evaluation of malignancy. As a consequence, in recent years there has been a growing and persisting demand towards developing new non-invasive, practical diagnostic tools that might facilitate the early detection of oral cancer. The most investigated non-invasive adjunctive techniques are vital staining, autofluorescence, chemiluminescence, narrow band imaging, and exfoliative cytology. Aim of the review is to critically describe these adjunctive aids and, after considering the literature data, an expert opinion on the effectiveness and the possible use of each technique will be provided

Exploring the Gain of Function Contribution of AKT to Mammary Tumorigenesis in Mouse Models

Elevated expression of AKT has been noted in a significant percentage of primary human breast cancers, mainly as a consequence of the PTEN/PI3K pathway deregulation. To investigate the mechanistic basis of the AKT gain of function-dependent mechanisms of breast tumorigenesis, we explored the phenotype induced by activated AKT transgenes in a quantitative manner. We generated several transgenic mice lines expressing different levels of constitutively active AKT in the mammary gland. We thoroughly analyzed the preneoplastic and neoplastic mammary lesions of these mice and correlated the process of tumorigenesis to AKT levels. Finally, we analyzed the impact that a possible senescent checkpoint might have in the tumor promotion inhibition observed, crossing these lines to mammary specific p53(R172H) mutant expression, and to p27 knock-out mice. We analyzed the benign, premalignant and malignant lesions extensively by pathology and at molecular level analysing the expression of proteins involved in the PI3K/AKT pathway and in cellular senescence. Our findings revealed an increased preneoplastic phenotype depending upon AKT signaling which was not altered by p27 or p53 loss. However, p53 inactivation by R172H point mutation combined with myrAKT transgenic expression significantly increased the percentage and size of mammary carcinoma observed, but was not sufficient to promote full penetrance of the tumorigenic phenotype. Molecular analysis suggest that tumors from double myrAKT;p53(R172H) mice result from acceleration of initiated p53(R172H) tumors and not from bypass of AKT-induced oncogenic senescence. Our work suggests that tumors are not the consequence of the bypass of senescence in MIN. We also show that AKT-induced oncogenic senescence is dependent of pRb but not of p53. Finally, our work also suggests that the cooperation observed between mutant p53 and activated AKT is due to AKT-induced acceleration of mutant p53-induced tumors. Finally, our work shows that levels of activated AKT are not essential in the induction of benign or premalignant tumors, or in the cooperation of AKT with other tumorigenic signal such as mutant p53, once AKT pathway is activated, the relative level of activity seems not to determine the phenotype

Increase in immune cell infiltration with progression of oral epithelium from hyperkeratosis to dysplasia and carcinoma

In the present study, epithelium derived lesions of various pathological manifestations were examined histologically and immunohistochemically for mononuclear cell infiltration. The infiltrate under the transformed epithelium of oral lesions, was examined for differences in the composition of immune mononuclear cells as the epithelium moves from hyperkeratosis through various degrees of dysplasia to squamous cell carcinoma. The study was performed on 53 human tongue tissues diagnosed as hyperkeratosis (11 cases), mild dysplasia (nine cases), moderate and severe dysplasia (14 cases) and squamous cell carcinoma (19 cases). A similar analysis was performed on 30 parotid gland tissues diagnosed as pleomorphic adenoma (14 cases) and carcinoma ex-pleomorphic adenoma (16 cases). Immunohistochemical analysis of various surface markers of the tumour infiltrating immune cells was performed and correlated with the transformation level as defined by morphology and the expression of p53 in the epithelium. The results revealed that, in the tongue lesions, the changes in the epithelium from normal appearance to transformed were accompanied by a corresponding increase in the infiltration of CD4, CD8, CD14, CD19+20, and HLA/DR positive cells. The most significant change was an increase in B lymphocytes in tongue lesions, that was in accordance with the transformation level (P<0.001). In the salivary gland, a significant number of cases did not show an infiltrate. In cases where an infiltrate was present, a similar pattern was observed and the more malignant tissues exhibited a higher degree of immune cell infiltration

p53 and MDM2 protein expression in actinic cheilitis

Actinic cheilitis is a potentially malignant lip lesion caused by excessive and prolonged exposure to ultraviolet radiation, which can lead to histomorphological alterations indicative of abnormal cell differentiation. In this pathology, varying degrees of epithelial dysplasia may be found. There are few published studies regarding the p53 and MDM2 proteins in actinic cheilitis. Fifty-eight cases diagnosed with actinic cheilitis were histologically evaluated using Banóczy and Csiba (1976) parameters, and were subjected to immunohistochemical analysis using the streptavidin-biotin method in order to assess p53 and MDM2 protein expression. All studied cases expressed p53 proteins in basal and suprabasal layers. In the basal layer, the nuclei testing positive for p53 were stained intensely, while in the suprabasal layer, cells with slightly stained nuclei were predominant. All cases also tested positive for the MDM2 protein, but with varying degrees of nuclear expression and a predominance of slightly stained cells. A statistically significant correlation between the percentage of p53 and MDM2-positive cells was established, regardless of the degree of epithelial dysplasia. The expression of p53 and MDM2 proteins in actinic cheilitis can be an important indicator in lip carcinogenesis, regardless of the degree of epithelial dysplasia

Quantification of cell cycle markers in oral precancer

The overall aims of the studies were to obtain objective measures of oral precancerous lesions based upon studies of the cell cycle and to investigate these parameters as possible prognostic indicators with regard to malignant transformation of these lesions. The majority of the precancerous lesions in the present study were dysplastic. These are the lesions which cause the greatest concern clinically with regard to malignant transformation. The first part of the study investigated the S-phase, growth fraction and the relationship of these to each other and with the degree of dysplasia with the aim of achieving objective measurements of the dysplasia and prognostic information. This was achieved by the use of BrdU for labelling of cells in the S-phase and anti-Ki67 antibody as a marker of cells in the growth fraction. The BrdU labelling index was demonstrated to provide an objective assessment of the dysplastic lesions when compared to the semi-objective method of Smith and Pindborg (1969). The ratio of the S-phase to the growth fraction was higher in those lesions which progressed to malignancy and was cited as a possible prognostic indicator. A number of methodological problems were identified from this first part of the study and these were investigated further by the development of techniques in Chapter 3. Firstly, a method was developed to enable the BrdU labelled tissue to be formalin fixed and then allow other cell cycle associated markers to be studied on sequential sections of the same tissue block. Secondly, numerous antigen retrieval techniques were carried out in order to optimise the immunohistochemical staining of Ki67 and subsequently other antibodies utilised in later parts of the study. Normal oral epithelium, derived post-mortem, was studied in Chapter 4 to investigate the apparent underestimation of proliferating cells identified by anti-Ki67 antibody in Chapter 2. It was apparent that, as in dysplastic epithelia, Ki67 significantly underestimated progenitor cells of the morphologically identified progenitor compartment. Ki67 did not identify all of those cells which would have been expected to be in the cell cycle it was originally claimed to do