The Expression of Testin, Ki-67 and p16 in Cervical Cancer Diagnostics.

Testin is a protein expressed in normal human tissues, being responsible, with other cytoskeleton proteins, for the proper functioning of cell−cell junction areas and focal adhesion plaques. It takes part in the regulation of actin filament changes during cell spreading and motility. Loss of heterozygosity in the testin-encoding gene results in altered protein expression in many malignancies, as partly described for cervical cancer. The aim of our study was the assessment of the immunohistochemical (IHC) expression of testin in cervical cancer and its analysis in regard to clinical data as well the expression of the Ki-67 antigen and p16 protein. Moreover, testin expression was assessed by Western blot (WB) in commercially available cell lines. The IHC analysis disclosed that the expression of testin inversely correlated with p16 (r = −0.2104, p < 0.0465) and Ki-67 expression (r = −0.2359, p < 0.0278). Moreover, weaker testin expression was observed in cancer cases vs. control ones (p < 0.0113). The WB analysis of testin expression in the cervical cancer cell lines corresponded to the IHC results and showed a weaker expression compared to that in the control cell line. When we compared the expression of testin in cervical cancer cell lines, we found a weaker expression in HPV-negative cell lines. In summary, we found that the intensity of testin expression and the number of positive cells inversely correlated with the expression of Ki-67 (a marker of proliferation) and p16 (a marker of cell cycle dysregulation). This study shows that the combined assessment of testin, Ki-67 and p16 expression may improve cervical cancer diagnostics.

The Immunohistochemical Expression of Epithelial-Mesenchymal Transition Markers in Precancerous Lesions and Cervical Cancer.

In the epithelial-mesenchymal transition (EMT) process, cells lose their epithelial phenotype and gain mesenchymal features. This phenomenon was observed in the metastatic phase of neoplastic diseases, e.g., cervical cancer. There are specific markers that are expressed in the EMT. The aim of this study was to determine the localization of and associations between the immunohistochemical (IHC) expression of TWIST, SNAIL, and SLUG proteins in precancerous lesions and cervical cancer. The IHC analysis disclosed higher expressions of EMT markers in precancerous lesions and cervical cancer than in the control group. Moreover, stronger expression of TWIST, SNAIL, and SLUG was observed in cervical intraepithelial neoplasia grade 3 (CIN3) vs. CIN1, CIN3 vs. CIN2, and CIN2 vs. CIN1 cases (p < 0.05). In cervical cancer, IHC reactions demonstrated differences in TWIST, SNAIL, and SLUG expression in grade 1 (G1) vs. grade 2 (G2) (p < 0.0011; p < 0.0017; p < 0.0001, respectively) and in G1 vs. grade 3 (G3) (p < 0.0029; p < 0.0005; p < 0.0001, respectively). The results of our study clearly showed that existing differences in the expression of the tested markers in precancerous vs. cancerous lesions may be utilized in the diagnosis of cervical cancer. Further studies on bigger populations, as well as in comparison with well-known markers, may improve our outcomes.

The Immunohistochemical Expression of MCM-3, -5, and -7 Proteins in the Uterine Fibroids.

Uterine fibroids are the most common mesenchymal uterine neoplasms; their prevalence is estimated in 40%-60% of women under 35 and in 70%-80% of women over 50 years of age. The current research aims to focus on the etiopathogenesis of uterine fibroids, the factors that affect their growth, and markers with diagnostic and prognostic properties. The MCM (minichromosome maintenance) protein family consists of peptides whose primary function is participation in the molecular mechanism of creating replication forks while regulating DNA synthesis. The aim of this work was to determine the proliferative potential of uterine fibroid cells based on the expression of the Ki-67 antigen and the MCMs-i.e., MCM-3, MCM-5, and MCM-7. In addition, the expression of estrogen (ER) and progesterone (PgR) receptors was evaluated and correlated with the expression of the abovementioned observations. Ultimately, received results were analyzed in terms of clinical and pathological data. MATERIALS AND METHODS: In forty-four cases of uterine fibroids, immunohistochemical reactions were performed. A tissue microarray (TMA) technique was utilized and analyzed cases were assessed in triplicate. Immunohistochemistry was performed using antibodies against Ki-67 antigen, ER, PgR, MCM-3, MCM-5, and MCM-8 on an automated staining platform. Reactions were digitalized by a histologic scanner and quantified utilizing dedicated software for nuclear analysis. Assessment was based on quantification expression of the three histiospots, each representing one case in TMA. RESULTS: In the study group (uterine fibroids), statistically significant stronger expression of all the investigated MCMs was observed, as compared to the control group. In addition, moderate and strong positive correlations were found between all tested proliferative markers. The expression of the MCM-7 protein also correlated positively with ER and PgR. With regard to clinical and pathological data, there was a negative correlation between the expression of MCMs and the number of both pregnancies and births. Significant reductions in MCM-5 and MCM-7 expression were observed in the group of women receiving oral hormonal contraceptives, while smoking women showed an increase in MCM-7, ER, and PgR. CONCLUSIONS: Uterine fibroid cells have greater proliferative potential, as evaluated by expression of the Ki-67 antigen and MCMs, than unaltered myometrial cells of the uterine corpus. The expression of MCM-7 was found to have strong or moderate correlations in all assessed relations. In the context of the clinical data, as well evident proliferative potential of MCMs, further studies are strongly recommended.

The Usefulness of Immunohistochemistry in the Differential Diagnosis of Lesions Originating from the Myometrium.

Uterine leiomyomas (LMs), currently the most common gynecological complaint around the world, are a serious medical, social and economic problem. Accurate diagnosis is the necessary prerequisite of the diagnostic-therapeutic process. Statistically, mistakes may occur more often in case of disease entities with high prevalence rates. Histopathology, based on increasingly advanced immunohistochemistry methods, is routinely used in the diagnosis of neoplastic diseases. Markers of the highest sensitivity and specificity profiles are used in the process. As far as LMs are concerned, the crux of the matter is to identify patients with seemingly benign lesions which turn out to be suspicious (e.g., atypical LM) or malignant (e.g., leiomyosarcoma (LMS)), which is not uncommon. In this study, we present the current state of knowledge about the use of immunohistochemical markers in the differential diagnosis of LM, atypical LM, smooth muscle tumors of uncertain malignant potential (STUMP), and LMS, as well as their clinical predictive value.

The Role of Tumor Necrosis Factor α in the Biology of Uterine Fibroids and the Related Symptoms.

Uterine fibroids (UFs) are the most common benign tumors of the female genital tract. The incidence of UFs has been estimated at 25⁻80% depending on selected population. The pathophysiology of UFs remains poorly understood. The transformation of smooth muscle cells of the uterus into abnormal, immortal cells, capable of clonal division, is the main component of all pathways leading to UF tumor formation and tumor necrosis factor α (TNF-α) is believed to be one of the key factors in this field. TNF-α is a cell signaling protein involved in systemic inflammation and is one of the cytokines responsible for the acute phase reaction. This publication presents current data about the role of tumor necrosis factor α in the biology of UFs and the related symptoms. TNF-α is an extremely important cytokine associated with the biology of UFs, UF-related symptoms and complaints. Its concentration has been proven to be elevated in women with clinically symptomatic UFs. The presented data suggest the presence of an "inflammation-like" state in women with UFs where TNF-α is a potent inflammation inducer. The origin of numerous symptoms reported by women with UFs can be traced back to the TNF-α influence. Nevertheless, our knowledge on this subject remains limited and TNF-α dependent pathways in UF pathophysiology should be investigated further.

Podoplanin Expression Correlates with Disease Progression in Mycosis Fungoides.

The aim of this study was to investigate the role of lymphangiogenesis in the clinical progression and outcome of mycosis fungoides. Immunohistochemistry and Western blot techniques were used to assess the expression of podoplanin and vascular endothelial growth factor C in mycosis fungoides. Expression of vascular endothelial growth factor C measured by immunohistochemistry was significantly higher in mycosis fungoides samples in comparison with control cases (chronic benign dermatoses) (p = 0.0012). Increased expression of podoplanin was found in advanced vs. early mycosis fungoides (p < 0.0001), and was positively correlated with cutaneous and nodal involvement (p < 0.001, p < 0.0001; respectively). Higher podoplanin expression was also significantly associated with shorter survival (p < 0.001). Strong positive correlation was observed between expression of podoplanin analysed by immunohistochemistry and Western blot (r = 0.75, p < 0.0001). A similar association was shown regarding expression of vascular endothelial growth factor C (r = 0.68, p = 0.0007). In conclusion, these results suggest that increased expression of podoplanin is associated with poor clinical course, as well as shorter survival, of patients with mycosis fungoides.

Expression of SOX18 in Mycosis Fungoides.

SOX18 is a transcription factor involved in the development of hair follicle, blood and lymphatic vessels, as well as regenerative processes. In addition, accumulated data indicate the role of SOX18 in tumourigenesis. So far, no studies on the role of SOX18 expression in mycosis fungoides (MF), the most common primary cutaneous T-cell lymphoma, have been performed. Therefore, we evaluated SOX18 expression in MF at the mRNA and protein level. SOX18 expression was observed predominantly on the blood and lymphatic vessels, in the intratumoural and peritumoural microenvironment of MF. The intra-tumoural, but not peritumoural, expression of SOX18 correlated positively with the advancement of the disease, cutaneous involvement and extracutaneous meta-stases at the protein level (p < 0.001, p < 0.001, p = 0.004; respectively). Significantly lower SOX18 mRNA expression was correlated with lymph node involvement (p = 0.01). In conclusion, we hypothesize that SOX18, as a marker of neovascularization, may be involved in the progression of MF.

Metallothioneins in Normal and Cancer Cells.

Metallothioneins (MTs) are low molecular weight proteins, which are present in almost all types of organisms. In mammals, four main MT isoforms designated from MT-1 to MT-4 were identified. Their biological role, according to their characteristic structure, was shown to be mostly associated with cellular metabolism of metal ions, especially zinc. Moreover, the available evidence suggests broad regulatory properties of MTs in the control of cell senescence and various pathological processes including neurodegeneration, cardiovascular pathology, metabolic disorders, and various malignancies. This extensive review provides general in formation on the structure of MT family members and the cellular functions of MT-1, MT-2, and MT-4 isoforms as well as insights into divergent biological roles of MT-3. Due to the involvement of MT molecules in various processes related to carcinogenesis, an organ-specific presentation of current data concerning their potential impact on the progression of various tumors is given. The regulatory role of MT family members in the function of the immune system is also discussed in depth.

[Angiogenesis and lymphangiogenesis in primary cutaneous T-cell lymphomas]. / Angiogeneza i limfangiogeneza w pierwotnie skórnych chloniakach T-komórkowych.

Primary cutaneous T-cell lymphomas are a group of rare hematologic malignancies, derived from mature T lymphocytes and initially developing only in the skin. The most common lymphomas representing this group are mycosis fungoides and Sezary syndrome. Mycosis fungoides is an indolent disease with a chronic course and characteristic evolution of the skin lesions from erythematous patches, through plaques to tumors. Sezary syndrome is characterized by an aggressive course and a triad of symptoms (erythroderma, generalized lymphadenopathy, and the presence of atypical cells in the skin, lymph nodes and peripheral blood). The etiopathogenesis of cutaneous lymphomas is not fully understood, but a few studies on angiogenesis and lymphangiogenesis in these malignancies indicate a significant role in their development and progression. Angiogenesis is a process of formation of new blood vessels from existing ones. Lymphangiogenesis is a similar process concerning lymphatic vasculature. Development of new vessels is a complex process composed of several successive stages: migration, proliferation, and differentiation of endothelial cells, extracellular matrix degradation and formation and stabilization of new vessels, regulated by growth factors, cytokines and other proteins. Both phenomena are essential in the development and progression of solid tumors and hematological malignancies. Therapeutic strategies involving the inhibition of tumor angiogenesis and lymphangiogenesis are a promising new direction of studies in antitumor therapy, requiring further experiments.

Increase of nuclear expression of metallothionein I/II in neoplastic transformation of the endomnetrium.

OBJECTIVES: The aim of our study was to investigate the expression of epidermal growth factor receptor (EGFR), metallothionein (MT) 1/11, and Ki-67 antigen in endometrial cancer We analyzed cytoplasmic (cMT) and nuclear (nMT) metallothionein fractions separately Moreover we evaluated the relationships between expressions of the above mentioned proteins and compared them with clinicopathologic data. MATERIAL AND METHODS: The study material included paraffin-embedded endometrial cancer samples from 84 patients. The control group consisted of 52 non-neoplastic endometrium samples. Immunohistochemical reactions were performed using monoclonal antibodies against EGFR, MT 1/11 and Ki-67. Expression intensity of the tested proteins was assessed by computer image analysis software. Chi-square, Spearman's correlation, Mann-Whitney and Kruskal-Wallis tests were used for statistical analysis with Statistica 8.0 PL. RESULTS: Strong expression of nMT was revealed in endometrial cancer cells in relation to benign hyperplasia (p<0.0017) and normal cells (p<0.001) of the endometrium. Statistically significant but weaker expressions in analogous relationships were observed for cMT Moreover higher grade of histological malignancy G was positively associated with increased expression of nMT (p=0.009). CONCLUSIONS: Expression of nMT remains in distinct correlation with neoplastic transformation of the endometrium and histologic grades. Our results clearly indicate a need for further research on metallothionein expression in tumor cells.

Expression of the MT1 melatonin receptor in ovarian cancer cells.

Ovarian cancer (OC) is the leading cause of death among women with genital tract disorders. Melatonin exhibits oncostatic properties which it may effect through binding to its membrane receptor, MT1. The aim of this study was to determine the expression of MT1 in OC cells and to correlate this with clinical and pathological data. Immunohistochemistry was performed on 84 cases of OC. Normal ovarian epithelial (IOSE 364) and OC (SK-OV-3, OVCAR-3) cell lines were used to examine the MT1 expression at protein level using the western blot and immunofluorescence technique. The expression of MT1 was observed as cytoplasmic-membrane (MT1(CM)) and membrane (MT1(M)) reactions. A positive correlation between MT1(CM) and MT1(M) was found in all the studied cases. There were no significant differences between the expression of MT1(CM), MT1(M), and histological type, staging, grading, presence of residual disease, or overall survival time. Immunofluorescence showed both MT1(M) and MT1(CM) expression in all the tested cell lines. Western blot illustrated the highest protein level of MT1 in IOSE 364 and the lowest in the OVCAR-3. The results indicate the limited prognostic significance of MT1 in OC cells.

Pre-Exposure Prophylaxis and Treatment with Tixagevimab/Cilgavimab for COVID-19 among Immunocompromised Pediatric Patients.

Background: Patients treated with hemato-oncological malignancies (HO) or undergoing cellular therapies such as hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T cells (CAR-T) were significantly affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the success of SARS-CoV-2 vaccination, immunocompromised patients remain at increased risk for severe coronavirus disease (COVID-19), rendering this group of population a high priority for additional prevention and treatment options. Tixagevimab and Cilgavimab (TIXA/CILGA, AZD7442, Evusheld®) is a combination of two fully human, long-acting monoclonal antibodies. TIXA/CILGA have been approved as pre-exposure prophylaxis and treatment in patients at risk of severe disease with impaired vaccine response. Our objective was to describe the efficacy and safety among immunocompromised pediatric patients. Methods: This was an observational multicenter cohort study of immunocompromised pediatric patients receiving TIXA/CILGA conducted at nine Polish centers of Pediatric Oncology, Hematology and Bone Marrow Transplantation. We analyzed patients in two groups; those treated with HO and those undergoing cellular therapies: HSCT or CAR-T cells. In addition, two other cohorts were identified: patients given TIXA/CILGA as pre-exposure prophylactic and therapeutic intervention. Results: A total of 78 patients were evaluated during the study period: 69 (88.5%) received TIXA/CILGA as pre-exposure prophylaxis and 9 (11.5%) as a treatment strategy. A total of 52 (66.6%) patients were treated with standard chemotherapy at HO departments; 21 (27%) underwent HSCT, and 5 (6.4%) received CAR-T cell therapy. All children with COVID-19 receiving TIXA/CILGA presented a mild degree of severity. The most common clinical manifestations were fever, cough and coryza. At least one adverse event (AE) was reported in two (3.8%) patients excluding standard injection site reactions. Reported AEs were mild or moderate in intensity. One child reported mild myalgia and one reported moderate bone pain and weakness. Conclusions: In our observational multicenter cohort study, we explored the use of TIXA/CILGA as pre-exposure prophylaxis and treatment for COVID-19 among immunocompromised pediatric patients. While our findings suggest a potential benefit in preventing and managing COVID-19 in this vulnerable population, it is important to note the study's non-comparative design. Our results highlight the need for well-designed clinical trials to confirm these observations and further assess the efficacy and safety of TIXA/CILGA in immunocompromised children.

Preliminary Study on the Expression of Testin, p16 and Ki-67 in the Cervical Intraepithelial Neoplasia.

Cervical cancer is one of the most common malignant cancers in women worldwide. The 5-year survival rate is 65%; nevertheless, it depends on race, age, and clinical stage. In the oncogenesis of cervical cancer, persistent HPV infection plays a pivotal role. It disrupts the expression of key proteins as Ki-67, p16, involved in regulating the cell cycle. This study aimed to identify the potential role of testin in the diagnosis of cervical precancerous lesions (CIN). The study was performed on selected archival paraffin-embedded specimens of CIN1 (31), CIN2 (75), and CIN3 (123). Moderate positive correlation was observed between testin and Ki-67 as well as testin and p16 expression in all dysplastic lesions (r = 0.4209, r = 0.5681; p < 0.0001 for both). Statistical analysis showed stronger expression of the testin in dysplastic lesions vs. control group (p < 0.0001); moreover, expression was significantly higher in HSIL than LSIL group (p < 0.0024). In addition, a significantly stronger expression of testin was observed in CIN3 vs. CIN1 and CIN3 vs. CIN2. In our study, expression of Ki-67, p16, and testin increased gradually as the lesion progressed from LSIL to HSIL. The three markers complemented each other effectively, which may improve test sensitivity and specificity when used jointly.

The usefulness of periostin determination in gynecology and obstetrics.

Periostin (POSTN) is a multifunctional glycoprotein that belongs to the group of extracellular matrix (ECM) proteins. Due to the molecular structure, cellular interactions, tissue locations as well functions of POSTN, we realize that its pivotal role is organization and regulation of ECM microenvironment. In available databases there is a lack of data summarizing current knowledge about POSTN expression in the field of gynecology and obstetrics. We conducted a search in PubMed of the National Library of Medicine and Google Scholar. Databases were extensively searched for all original and review articles/book chapters published in English until December 2019 and related to periostin expression. All relevant articles were reviewed and presented as appropriate. In the field of POSTN expression there is only one paper evaluating its involvement in cervical cancer cell metabolism and only two studies analyzing its myometrial commitment: maintenance during pregnancy and induction of parturition in physiology as well control of fibroids biology in pathology. Much more attention has been devoted to the expression of described protein in the endometriosis, and above all in ovarian cancer. Finally, a few studies carried out among pregnant women were presented. In this review study we presented current knowledge about periostin expression in the field of gynecology and obstetrics. Many achieved results are interesting and further studies are needed to verify some hypotheses. Structure, signaling pathways as well many functions of periostin are well-described. However, as it was clearly shown there is a lot of unknown issues which are waiting to be explored.

Comparison of TMA Technique and Routine Whole Slide Analysis in Evaluation of Proliferative Markers Expression in Laryngeal Squamous Cell Cancer.

BACKGROUND/AIM: Comparison of the expression of Ki-67, MCM3, 5, 7 and MTI/II proteins using immunohistochemistry (IHC) on whole section (WS) and tissue microarray (TMA) of laryngeal squamous cell carcinoma (LSCC) samples. MATERIALS AND METHODS: A total of 51 archival paraffin blocks of LSCC were used. TMAs were prepared from 1.5 mm core punches. IHC reactions were performed using antibodies against Ki-67, minichromosome maintenance proteins (MCM3, 5, 7) and metallothionein (MTI/II). RESULTS: Spearman rank correlation test revealed moderate positive correlation in the case of Ki-67: WS vs. TMA (r=0.38, p=0.07) and strong positive correlation in regard to the rest of tested markers: MCM3, WS vs. TMA (r=0.49, p=0.0004); MCM5, WS vs. TMA (r=0.61, p<0.0001); MCM7, WS vs. TMA (r=0.59, p<0.0001); MTI/II, WS vs. TMA (r=0.66, p<0.0001). Mann Whitney U-test showed no significant differences in the case of Ki-67 and MCM5. Moreover, Bland-Altman test showed a low level of bias in regard to Ki-67, WS vs. TMA and MCM5, WS vs. TMA. CONCLUSION: TMA may be an effective and reliable method of assessment of Ki-67 and MCM5 expression in LSCC.

Effect of Physical Training on the Levels of Sex Hormones and the Expression of Their Receptors in Rats With Induced Mammary Cancer in Secondary Prevention Model - Preliminary Study.

BACKGROUND/AIM: Breast cancer is the most common malignant tumor among women worldwide. In previous work, we presented results of physical activity in primary prevention in a model of induced mammary gland cancer. In the present study, we assessed the influence of physical activity on sex hormone levels (estradiol and progesterone) and the expression of their receptors (ER, PR), as well as the level of apoptosis of tumor cells in secondary prevention. MATERIALS AND METHODS: Fifty 1-month-old female Sprague-Dawley rats received intraperitoneal injection of 180 mg/kg body weight of N-methyl-N-nitrosourea (MNU) for tumor induction. Three months after the administration of MNU, rats were divided into four groups: low-intensity, moderate-intensity, and high-intensity physical training groups (combined as PT) and a sedentary control (SC) group. Physical training was conducted 5 days per week with a three-position treadmill according to a precisely described protocol. The entire training was completed by 32 rats from which tissue and blood were collected for further analysis. Immunohistochemistry for ER and PR expression, terminal deoxynucleotidyl transferase dUTP nick-end labeling method for detection of apoptosis, and enzyme-linked fluorescent assay for detection of plasma hormone levels (estradiol and progesterone) were performed. Statistical analysis used p<0.05 as the significance level. RESULTS: Significantly stronger expression of ER and PR was found in the SC in comparison to the PT group (p=0.035 and p=0.036, respectively). No statistically significant differences were found in estradiol or progesterone concentrations between SC and PT groups. Apoptosis was non-significantly increased in the PT group in comparison with the SC group. Stronger apoptosis in the PT group correlated positively with the level of training intensity (r=0.35, p=0.05). CONCLUSION: Physical training may reduce ER and PR expression in breast cancer cells, and reduce cell sensitivity to pro-proliferative and anti-apoptotic effects of estrogens, ultimately leading to apoptosis.

The Role of Testin in Human Cancers.

Testin is a protein expressed in almost all normal human tissues. It locates in the cytoplasm along stress fibers being recruited to focal adhesions. Together with zyxin and vasodilator stimulated protein it forms complexes with various cytoskeleton proteins such as actin, talin and paxilin. They jointly play significant role in cell motility and adhesion. In addition, their involvement in the cell cycle has been demonstrated. Expression of testin protein level correlates positively with percentage of cells in G1 phase, while overexpression can induce apoptosis and decreased colony forming ability. Decreased testin expression associate with loss by cells epithelial morphology and gain migratory and invasive properties of mesenchymal cells. Latest reports indicate that TES is a tumor suppressor gene which can contribute to cancerogenesis but the mechanism of loss TES gene expression is still unknown. Some authors point out hypermethylation of the CpG island as a main factor, however loss of heterozygosity may also play an important role [4, 5]. The altered expression of testin was found in malignant neoplasm, i.a. ovarian, lung, head and neck squamous cell cancer, breast, endometrial, colorectal, prostate and gastric cancers [1-9]. Testin participate in the processes of tumor growth, angiogenesis, and metastasis [10]. Many researchers stated involvement of testin in tumor progression, what suggest its potential usage in immunotherapy [7, 11]. Understanding the molecular functions of testin may be crucial in development personalized treatment. In the present manuscript up-to-date review of literature can be found.

The large intestine from fetal period to adulthood and its impact on the course of colonoscopy.

The human large intestine in the living adult has a total length of about 1300 mm, ranging from 1100 to 2108 mm. The development of the gut continues after birth, up to the age 4-5. The large intestine ascends at the beginning in the right abdominal quadrant, then it traverses the abdominal cavity, and finally it descends to the anus. The left and right colic flexures are the basic flexions between the transverse, ascending and descending colon, respectively. Additionally, there are secondary bendings between intestinal segments. The angles between the neighbouring parts can vary between examined subjects. Most of the angulations can be found in the transverse (range 2-9) and sigmoid colon (range 1-9), making them the most troublesome parts to pass with a colonoscope. Colonoscopy (usually performed in the left lateral or supine position) is one of the most important examination of the large intestine mucus membrane. During this procedure the endoscope is passed through the colon into the cecum or terminal ilium. The individual anatomical features (tortuosity, supernumerary loops and elongation) may slow down or interfere with the progress of the scope. We summarize current knowledge on the human large intestine from the fetal period to adulthood and carve out some aspects that are currently less known to colonoscopists.

Matrix metalloproteinases-2, -7 and tissue metalloproteinase inhibitor-1 expression in human endometrium.

INTRODUCTION: Endometrium undergoes regular, cyclic tissue remodeling mostly associated to the endocrine system status. It is well-known fact that steroid hormones are strongly responsible for changes in endometrium. The precise mechanism of their action is still under investigation. The aim of the study was to evaluate the expression of metalloproteinases 2 and 7 (MMP-2, -7) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in human endometrium in relation to serum concentrations of estradiol and progesterone during different phases of menstrual cycle. MATERIAL AND METHODS: The study material consisted of 52 biopsy samples; 12 obtained in the proliferative phase, 11 in the secretory phase and 29 during menstruation. Expression of MMP-2, MMP-7 and TIMP-1 was assessed by immunohistochemistry. Serum concentrations of estradiol and progesterone at time of biopsy were evaluated by immunochemistry assay. Results of the study were statistically assessed by linear regression model. RESULTS: Increased serum concentration of estradiol was associated with increased MMP-2 expression in proliferative phase but decreased in secretory phase and during menstruation. No significant relationship was found between progesterone concentration and MMP-2 expression. Moreover, no difference in the expression of MMP-7 and TIMP-1 in the endometrium in relation to hormone levels and menstrual cycle phases were observed. CONCLUSIONS: The results of the study indicate that estradiol influence MMP-2 expression in the endometrium depends on the phase of menstrual cycle. Such relationships were not found for MMP-7 and TIMP-1 and further tests clarifying association between estradiol and MMPs are needed.

Expression of p16 and SATB1 in Invasive Ductal Breast Cancer - A Preliminary Study.

BACKGROUND/AIM: An impaired cell-cycle control and genetic material organization are crucial elements of carcinogenesis. p16 is a tumor suppressor protein which decelerates promotion of the cells from G1 to S phase, whereas special AT-rich sequence-binding protein 1 (SATB1) is a nuclear matrix protein that binds to specific regions of the DNA and ensures its proper organization and function. Increased levels of both markers are observed in various types of cancers. The aim of this study was to investigate the expression of p16 and SATB1 proteins in regard to expression of the Ki-67 antigen and available clinicopathological data (i.a. receptor status, staging and grading). MATERIALS AND METHODS: The study was performed on 130 samples of archived invasive ductal breast cancers. Immunohistochemical reactions were performed on freshly prepared tissue microarrays and subsequently scanned by a histologic scanner. Reactions were evaluated separately in the cytoplasm (p16c, SATB1c) and nucleus (p16n, SATB1n, Ki-67) with use of a quantification software under researcher supervision. RESULTS: Expression was observed for Ki-67 in 100%, p16c in 90%, p16n in 89.2%, SATB1c in 98.5% and SATB1n in 87.7% of cancer cases. Statistical analysis showed strong positive correlations: p16c vs. p16n and SATB1c vs. SATB1n (p<0.001 for both) and weak positive correlations: p16c vs. SATB1c and p16c vs. SATB1n (p=0.008, p=0.027; respectively). Expression of p16n was stronger in G1 vs. G2 (p=0.034) while Ki-67 expression was stronger in cases with negative progesterone receptor status (p=0.011). All other analyzed associations were statistically insignificant. CONCLUSION: A weak association between immunohistochemical expression of p16 and SATB1 indicated limited possibility of their independent usage. Further studies concerning determination of a wider panel of proteins controlling cell cycle should be considered.