E-cadherin adhesion molecule and syndecan-1 expression in various thyroid pathologies

Cadherins and syndecans are transmembrane glycoproteins implicated in cell-cell and cell-matrix adhesion. Impairment of cadherin and syndecan mediated adhesion is likely to constitute one of the main factors leading to the reduced cell-cell and cell-matrix adhesion characteristics of tumor cells and play a pivotal role in the acquisition of invasive and metastatic proprieties by neoplastic epithelial cells. Aim: To elucidate the role and alterations of syndecan-1 expression in comparison with those of E-cadherin in normal and pathological thyroid glands (TG). Methods: A total of 55 TG carcinomas, 40 TG adenomas, 40 cases of hyperplastic TG disorders and 20 cases of normal TG autopsy samples, were evaluated by immunohistochemistry. The staining intensity, and localization of syndecan-1 and E-cadherin in sequential sections were examined, and semi-quantified. Results: Immunostaining of syndecan-1 and E-cadherin was strong in normal follicular TG epithelial cells, and located mainly in basolateral membrane. No significant change was seen in either molecule in hyperplastic TG disorders compared with TG adenomas. A significant reduction in expression of both syndecan-1 and E-cadherin was seen in well-differentiated TG carcinomas as compared with normal TG epithelium (p = 0.0001 and p = 0.032, respectively). Similarly, there was a significant reduction of both molecules expression in poorly differentiated and anaplastic TG carcinomas compared to well differentiated tumors (syndecan-1: p = 0.0037; and E-cadherin: p = 0.075). Conclusion: Decreased E-cadherin and syndecan-1 expression along with decreasing cellular differentiation may be involved in the complex mechanism of progression of TG pathology.Кадгерины и синдеканы — это трансмембранные гликопротеины, участвующие в межклеточной адгезии и адгезии клеток к матриксу. Изменения экспрессии этих молекул играют главную роль в приобретении инвазивного и метастатического потенциала злокачественно трансформированными эпителиальными клетками. Цель: оценка роли экспрессии синдекана-1 и Е-кадгерина в ткани щитовидной железы в норме и при патологии. Методы: образцы ткани для иммуногистохимического исследования взяли у 55 больных раком щитовидной железы (ЩЖ), 40 пациентов — с аденомой ЩЖ, 40 — с гиперпластическими процессами ЩЖ, контролем служили 20 образцов неизмененной ткани ЩЖ (аутопсия). Результаты: экспрессия синдекана-1 и Е-кадгерина в нормальных фолликулярных эпителиальных клетках ЩЖ выражена интенсивно, с преимущественной локализацией в базолатеральной мембране. Не отмечали существенных различий в экспрессии обеих молекул при гиперпластических процессах по сравнению с аденомами ЩЖ. Однако таковая значительно снижена в образцах высокодифференцированной карциномы по сравнению с нормальным эпителием ЩЖ (p = 0,0001 и p = 0,032 соответственно), а также при низкодифференцированном и анапластическом раке по сравнению с высокодифференцированными опухолями ЩЖ (p = 0,0037 для синдекана-1 и p = 0,075 для Е-кадгерина). Выводы: снижение экспрессии синдекана-1 и Е-кадгерина, сопровождающееся снижением способности клеток к дифференциации, может быть частью механизма прогрессирования заболеваний ЩЖ

Molecular profiling and genomic microarrays in prostate cancer

In the present review article a global approach regarding the usefulness of genomic microarrays in prostate cancer management, is attempted. Cancer is a multistep process of mutations in key regulatory genes and epigenetic alterations that result in loss of balanced gene expression. A complete knowledge of the interaction between the genetic variability of the neoformation (tumor profiling) and the genetic variability of the host (inherited genome profiling), will be able to determine the better strategy against the cancer and the less toxicity for the patient. Alterations in the sequence of the hormone binding domain of the androgen receptor as well as mutations in some genes, determine radioresistance and resistance or sensitivity to some chemotherapeutic drugs. New therapies using monoclonal antibodies directed against specific extracellular binding domains of some receptors are based on molecular alterations observed in tumors.В обзоре обсуждается целесообразность применения геномных микрочипов для выявления рака предстательной железы. Рак является многоэтапным процессом мутаций в ключевых регуляторных генах и эпигенетических изменений, приводящих к утрате сбалансированной экспрессии генов. Фундаментальные знания о взаимосвязи между генетической вариабельностью опухолевых клеток (молекулярном профиле опухоли) и генетической вариабельностью хозяина (наследуемый геномный профиль) позволит выбрать наилучшую стратегию противоопухолевой терапии при низкой токсичности таковой. Изменения последовательности гормонсвязывающего домена рецептора андрогена наряду с мутациями некоторых генов определяют устойчивость к лучевой терапии и устойчивость или чувствительность к ряду химиопрепаратов. Новые виды терапии с использованием моноклональных антител против специфичных внеклеточных связывающих доменов ряда рецепторов основаны на данных о молекулярных особенностях новообразований

Amplification and co-regulators of androgen receptor gene in prostate cancer

Prostate cancer isthe second most common malignancy among males after lung cancer. The growth of prostate cancer cells depends on the presence of androgens, a group ofsteroid hormones that include testosterone and its more active metabolite dihydrotestosterone. Most prostate cancers are androgen-dependent and respond to the antiandrogens or androgen-deprivation therapy. However, the progression to an androgen-independent stage occurs frequently. Possible mechanisms that could be involved in the development of hormone resistant prostate cancer causes including androgen receptor (AR) mutations, AR amplification/over expression, interaction between AR and other growth factors, and enhanced signaling in a ligand-independent manner are discussed

Selenium in serum and neoplastic tissue in breast cancer: correlation with CEA

Trace element selenium (Se) is regarded to be a breast cancer preventive factor involved in multiple protective pathways. In all, 80 women with breast cancer who underwent a radical mastectomy were enrolled in the study. Serum Se and carcinoembryonic antigen levels were measured using a fluorometric and IRMA assay, respectively. Se tissue concentration was determined by a tissue extracting fluorometric assay. For statistical analysis purposes t-test was used and P-values <0.001 were regarded as statistically significant. Serum Se was 42.5±7.5 μg l−1 in breast cancer patients and 67.6±5.36 μg l−1 in the age-matched control group of healthy individuals. Serum carcinoembryonic antigen in patients was 10±1.7 U ml−1 (normal <2.5 U ml−1 in nonsmokers/<3.5 U ml−1 in smokers). A statistically significant difference was found for both serum Se and CEA between two groups studied (P<0.001). Neoplastic tissue Se concentration was 2660±210 mg g−1 tissue; its concentration in the adjacent non-neoplastic tissue was 680±110 mg g−1 tissue (P<0.001). An inverse relationship between Se and CEA serum levels was found in the two groups studied (r=−0.794). There was no correlation between serum/tissue Se concentration and stage of the disease. The decrease in serum Se concentration as well as its increased concentration in the neoplastic breast tissue is of great significance. These alterations may reflect part of the defence mechanisms against the carcinogenetic process

Glycoprotein CD44 expression in benign, premalignant and malignant epithelial lesions of the larynx: An immunohistochemical study including correlation with Rb, p53, Ki-67 and PCNA

CD44 is an integral membrane glycoprotein that has diverse functions in cell-cell and cell-substrate interactions. It has been suggested that it may be a determinant of metastatic and invasive behavior in carcinomas. The immunohistochemical expression of CD44 was examined in a series of 34 squamous cell carcinomas, 13 in situ carcinomas, 35 cases with various degrees of epithelial dysplasia, 10 papillomas and 17 cases of keratosis. We used the monoclonal mouse antihuman phagocytic glycoprotein-1 CD44 (clone DF 1485), on formalin-fixed, paraffin-embedded tissue. CD44 expression was correlated with the expression of Rb and p53 proteins, with the proliferative indices Ki-67 and PCNA as well as with conventional clinicopathological data. The mean value of CD44 expression was 78.84 in squamous cell carcinomas, 78.04 in in situ carcinomas, 54.93 in dysplasia, 26.8 in papillomas and 24.97 in keratosis. There was no significant difference of CD44 expression between in situ and invasive carcinomas. However, a strong difference of reaction between carcinomas and the other cases was observed. CD44 expression was statistically higher in dysplastic lesions than the cases of keratosis (p&lt;0.0001) and papillomas (p=0.01). In the group of invasive carcinomas, CD44 expression was statistically correlated with pRb (p=0.011), while in preinvasive lesions it was correlated with PCNA (p=0.016). The relationship with the degree of dysplasia or grade of carcinoma and p53 protein expression was insignificant.These observations suggest that CD44 expression may be involved in the multiple mechanism of the development and progression of laryngeal lesions and may help to predict the risk of transformation of the benign or precancerous lesions to cancer

Glycoprotein CD44 expression in benign, premalignant and malignant epithelial lesions of the larynx. An immunohistochemical study including

CD44 is an integral membrane glycoprotein that has diverse functions in cell-cell and cell-substrate interactions. It has been suggested that it may be a determinant of metastatic and invasive behavior in carcinomas. The immunohistochemical expression of CD44 was examined in a series of 34 squamous cell carcinomas, 13 in situ carcinomas, 35 cases with various degrees of epithelial dysplasia, 10 papillomas and 17 cases of keratosis. We used the monoclonal mouse antihuman phagocytic glycoprotein-1 CD44 (clone DF 1485), on formalin-fixed, paraffin-embedded tissue. CD44 expression was correlated with the expression of Rb and p53 proteins, with the proliferative indices Ki-67 and PCNA as well as with conventional clinicopathological data. The mean value of CD44 expression was 78.84 in squamous cell carcinomas, 78.04 in in situ carcinomas, 54.93 in dysplasia, 26.8 in papillomas and 24.97 in keratosis. There was no significant difference of CD44 expression between in situ and invasive carcinomas. However, a strong difference of reaction between carcinomas and the other cases was observed. CD44 expression was statistically higher in dysplastic lesions than the cases of keratosis (p<0.0001) and papillomas (p=0.01). In the group of invasive carcinomas, CD44 expression was statistically correlated with pRb (p=0.011), while in preinvasive lesions it was correlated with PCNA (p=0.016). The relationship with the degree of dysplasia or grade of carcinoma and p53 protein expression was insignificant. These observations suggest that CD44 expression may be involved in the multiple mechanism of the development and progression of laryngeal lesions and may help to predict the risk of transformation of the benign or precancerous lesions to cancer

Expression of matrix metalloproteinase-9 (gelatinase B) in benign, premalignant and malignant laryngeal lesions

The matrix metalloproteinases (MMPs) are a family of proteolytic zinc-containing enzymes, which are responsible for the breakdown of the extracellular matrix components in pathological and physiological conditions. They are involved in basement membrane disruption, stroma and blood vessel penetration, metastasis and more recently there is evidence that they participate in tumor growth and angiogenic events. Matrix metalloproteinase 2 and 9 (MMP 2 and 9) belong to the gelatinases, a subgroup of MMPs, and have the capacity to degrade the triple helix type IV collagen of basal lamina of the basement membrane. With the present study, we tried to demonstrate the expression of MMP-9 immunohistochemically, comparatively in benign, premalignant and malignant lesions of the larynx. We studied 154 laryngeal lesions including 55 squamous cell carcinomas, 8 in situ carcinomas, 54 cases of dysplasia (of low and intermediate grade), 13 papillomas and 24 cases of keratosis. Overexpression of MMP 9 was observed in 74.4% and 50% in invasive and in situ squamous cell carcinomas respectively. In dysplastic cases, in papillomas and in keratoses the percentage of overexpression was 62.9%, 61.53% and 54.16% respectively and the expression of MMP-9 was significantly higher in invasive squamous cell carcinomas compared to dysplasias (p=0.000004). Also significantly higher was the expression of MMP-9 in dysplastic cases compared to papillomas (p=0.023). The MMP-9 expression was related neither to survival nor to the other available clinicopathological parameters (tumor size, grade, clinical stage, lymph node status and patient age). In conclusion, our study indicates that the expression of MMP-9 is up-regulated in a stepwise fashion, with two main steps, the first one, when a dysplastic lesion evolves and the next one, when the dysplasia progresses to invasive carcinoma