Epidermal Growth Factor Receptor immunohistochemical expression in hepatocellular carcinoma without Epidermal Growth Factor Receptor exons 18-21 mutations.

Introduction: EGFR targeted therapies, have been proved beneficial for patients with HCC, nevertheless additional research on EGFR immunoexpresion and EGFR mutations is still needed, especially in population in which it has not been done yet. The aim of this study is to evaluate EGFR immunoexpression in HCC without EGFR exons 18-21 mutations and to evaluate its influence on survival in HCC patients in North Macedonia. Methods: We studied 31 cases of HCC for EGFR immunohistochemical expression and EGFR exons 18-21 mutations. The following clinical parameters were analyzed: Hepatitis B and C virus infection, presence of cirrhosis, tumor size, enlarged lymph nodes, metastases, alpha fetoprotein level and overall survival. Presence of the EGFR immunosignal (membranous and cytoplasmic) and the percentage of positive tumor cells in the entire tumor tissue specimen were semi-quantitatively determined. Results: Hepatitis B and C virus infection, tumor size, metastatic disease and EGFR immunoexpression have influence on patient's survival. No EGFR exons 18-21 mutations were detected in this group of HCCs. EGFR expression of 61%-80% in tumor tissue significantly influenced survival of the patients (p < 0.01). Multiple Cox regression confirmed tumor size of 5-10 cm (p < 0.05), tumor size > 10 cm (p < 0.01) and EGFR expression in range of 61% to 80% (p < 0.05) as independent survival predictors in patients with HCC. Conclusion: EGFR overexpression in range of 61% to 80% was an independent survival predictor in patients with HCC, implying that these patients could benefit from EGFR inhibition. However, the absence of EGFR mutations in exons 18-21 in any of the cases of this study suggest that single drug EGFR targeted therapy in patients with HCC may be insufficient.

Effect of bladder cancer variant histology on survival outcome in patients treated with radical cystectomy: A single-centre experience.

CONTEXT: Bladder cancer (BC) is the sixth most common malignant neoplasm in men. Recently, great effort has been devoted to the study of BC variant histology (VH). Yet, the results from these studies have shown conflicting data and remain unclear whether their presence alters recurrence and survival rates after radical cystectomy (RC). AIMS: We undertook this study aiming to test the effect on VH on recurrence-free survival (RFS) and overall survival (OS) in single-center RC patients. SETTINGS AND DESIGN: We have retrospectively analyzed medical records and pathology reports from 331 patients who underwent RC with or without pelvic lymphadenectomy at University Urology Clinic-Skopje, North Macedonia, in the period between 2010 and 2018. SUBJECTS AND METHODS: Microscopic analysis of the specimens involved the evaluation of histological tumor type, tumor grade, pathological tumor node metastasis stage, presence of lymphovascular invasion, and resection margin status. STATISTICAL ANALYSIS USED: Univariable and multivariable Cox regression models were applied to test the effect of VH on RFS and OS. RESULTS: We found 185 patients who matched our inclusion criteria. At multivariable analyses, lymphovascular invasion and positive resection margins were associated with shorter RFS. Similarly, patients diagnosed with lymphovascular invasion, positive resection margins, and a pelvic lymph node metastasis had poorer OS. VH was not found to be an independent predictor of both RFS and OS (P > 0.05). CONCLUSIONS: The present study did not reveal prognostic effect of VH on RFS and OS. In our series, histomorphologic parameters including lymphovascular invasion, resection margins, and pelvic lymph node metastasis were the most relevant predictors on survival outcome after RC.

Percutaneous Imaging-Guided versus Open Musculoskeletal Biopsy: Concepts and Controversies.

Bone and soft tissue tumors are a largely heterogeneous group of tumors. Biopsy of musculoskeletal (MSK) tumors is sometimes a challenging procedure. Although the open biopsy is still considered the gold standard for the biopsy of MSK lesions, core needle biopsy can replace it in most cases, with similar accuracy and a low complication rate. The biopsy should be performed in a tertiary sarcoma center where the multidisciplinary team consists of at minimum a tumor surgeon, an MSK pathologist, and an MSK radiologist who can assess all steps of the procedure. Several factors can influence the success of the biopsy including the lesion characteristics, the equipment, and the method used for the procedure. This review highlights some of the important aspects regarding the biopsy of the MSK tumors, with special attention to imaging a guided core needle biopsy and highlighting some of the recent advancements and controversies in the field.

Late Onset of Pancreatic Metastases from Renal Cell Carcinoma. A Case Report.

Metastasis of renal cell carcinoma (RCC) to the pancreas is a rare entity accounting only 0.25-3% of all pancreatic tumors. We present a rare case of isolated three focal pancreatic metastases from RCC, occurring 15 years after the left nephrectomy. The majority of the pancreatic metastases are asymptomatic, as it was in case of our patient excluding the weight loss for the last three months. We demonstrate the importance of the medical history, radiological examinations, histological and immunohistochemical analysis in making a definitive diagnosis.

Mandibular involvement of plasmacytoma - Uncommon case report of rare entity.

Solitary plasmacytoma (SP) is an early-stage plasma cell malignancy that is in between monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) along the spectrum of plasma cell disorders. SPs can be divided into 2 groups according to location: solitary bone plasmacytoma (SBP) - these occur most commonly in the vertebrae and secondarily in long bones, and extramedullary plasmacytoma (EMP) - these encompass all nonosseus SPs. The etiology is still unknown, and they generally display a destructive course with preponderance of males. Both lesions present a risk of progression to multiple myelom. Its presence in jaws is extremely rare and when it is seen, angulus and ramus mandible are most common sites of occurrence. Histopathological examination and systemic investigation are mandatory for confirmation but support of immunohistochemistry positivity for CD138 was also done for establishing the final diagnosis.

Assessment of Density of Neovascularization in Lower Lip Squamous Cell Carcinoma in Relation To Neoplasm Differentiation Grade in Patients with and without Neck Lymph Nodes Metastasis.

BACKGROUND: Squamous cell carcinoma (SCC) of the lower lip is a relatively rare carcinoma, with the incidence of 1 to 2%, but it is the most common carcinoma in the oral cavity accounting for 25-30% of all malignant oral tumours. AIM: This study aimed to determine the role of neovascularisation in the process of tumour progression. METHODS: We analysed the surgical specimens obtained from 60 patients with squamous cell carcinoma (SCC) of the lower lip. The examined group consisted of 45 specimens of patients without metastasis and 15 specimens of patients with metastasis in the regional lymph nodes. Histopathological slides were immunohistochemically stained with an antibody against CD34 and by hematoxylin & eosin staining for routine histopathological examination. RESULTS: The results obtained showed a statistically significant difference in the density of neovascularisation between groups of the SCC with different grade of differentiation (Kruskal-Wallis test: H (2, N = 60) = 30.0943, p = 0.00001). Statistical analysis also showed a significant difference in the density of vascularisation of lower lip SCC between patients without metastasis and patients with neck metastasis (Mann-Whitney U test, p = 0.000198). Applying Pearson's chi-square test, we found a highly significant statistical difference in grade of SCC differentiation in patients with and without neck metastasis (p = 0.0000). CONCLUSION: In conclusion, the density of neoangiogenesis is increased in tumours with poorer differentiation and in patients with neck metastasis. So, the density of neovascularisation of the primary lip SCC may predict the tumour progression.

Hepatocellular carcinoma - clinicopathological characteristics, survival, and expression of various histologic molecular markers.

The aim of this study was to make a clinical characterisation of patients with hepatocellular carcinoma and to investigate the expression of a set of molecular markers in patients from the Republic of North Macedonia. We analysed 60 patients for clinicopathologic factors, and we investigated tumour tissue and surrounding liver tissue for immunoexpression of E-cadherin, ß-catenin, cyclin D1, and p53. Infection with hepatitis virus B and C (p < 0.001), tumour dimension (p < 0.001), vascular invasion (p < 0.002), and tumour differentiation (p < 0.021) significantly influenced the survival of the patients. E-cadherin and ß-catenin expression reduction and cyclin D1 and p53 overexpression were significantly higher in the tumour than in the non-tumour tissue (p < 0.001; p < 0.001; p = 0.001; p < 0.001, respectively). No significant correlation was found between clinicopathological characteristics and the analysed molecules nor between the molecules themselves. The immunoexpression of E-cadherin, ß-catenin, cyclin D1, and p53 was not related to the tumour aggressiveness and prognosis. However, their significantly higher expression in HCC tissue compared to that in non-tumour tissue indicate their important role in hepatocarcinogenesis. The clinicopathological characteristics of the neoplasm remain highly predictive factors for the survival of the patients.

Low-Grade Malignancy Glomus Tumor in a Setting of Multiple Glomus Tumors - Case Report.

BACKGROUND: Glomus tumors are rare neoplasms accounting for less than 2% of all soft tissue tumors but multiple lesions may be seen in up to 10% of the patients. Solitary glomus tumor (GT) most frequently appears as small nodule in specific locations such as subungual region or deep dermis. However, rarely these entities have been observed in extracutaneous locations such as the gastrointestinal, cardiovascular, respiratory tracts, and other visceral organs. A small fraction of the GTs may present as tumors of uncertain malignant potential or as malignant glomus tumors. CASE PRESENTATION: We report a patient with multiple glomus tumors on the time of diagnosis, which was histologically diagnosed as an atypical glomus tumor following resection of a tumor thrombus in the left renal vein, inferior vena cava trombus with intracardial extension, and mitral valve specimen. The intramuscular lesion from the thigh was diagnosed as a glomus tumor of uncertain malignant potential. Further examinations revealed multiple lesions trough her body: kidneys, breast, heart and subcutaneous tissue. The diagnosis of glomus tumor of uncertain malignant potential versus glomus tumor with low malignant potential could be quite challenging, and the clinical course may be as a determining factor for final diagnosis. CONCLUSION: To our knowledge, this is the only known case of glomus tumor with multiple organ involvement and aggressive biological behavior at presentation.

Tertiary Lymphoid Structures in Colorectal Cancers and Their Prognostic Value.

BACKGROUND: Tumor-infiltrating lymphocytes (TIL) in tumour stroma are considered to be involved in the elimination of malignant cells and prevention of metastasis formation. TIL consist of T lymphocytes including cytotoxic lymphocytes that are a constituent part of the effector mechanism of anti-tumour immunity and B lymphocytes that can form tertiary lymphoid structures (TLS). TLS has been described in several solid tumours and colorectal carcinoma (CRC), and the influence on the local and systemic anti-cancer response. AIM: This study aimed to quantify the presence of TLS in CRC patients and to determine their role in tumour progression. PATIENTS AND METHODS: The study included 103 patients with CRC who underwent surgery at the University Clinic of Digestive Surgery in Skopje, whose operative material was analysed at the Institute of Pathology, Medical Faculty in Skopje. The density of TLS was determined and correlated with the neoplasm status of local growth (T), positive lymph nodes, lymphatic invasion, and stage of the disease and tumour grade. RESULTS: The density of TLS was significantly higher in patients with higher stage, lower T status, and negative lymph nodes, in patients with no lymphatic invasion and with better-differentiated tumours. CONCLUSION: The density of TLS plays an important role in controlling the tumour growth, and it can be a parameter for neoplasm progression in CRC patients. The density of TLS influences the control of tumour progression.

EBV Positive Gastric Carcinomas and Their Clinicopathological Characteristics.

BACKGROUND: The understanding of the etiopathogenesis of gastric carcinoma (GC) can be a base for development of new therapeutic methods to reduce mortality and to increase survival in patients with GC. The percentage of Epstein - Barr virus (EBV) positive gastric carcinomas is uncertain, and the etiologic importance of EBV in the pathogenesis of GC has still not been elucidated. AIM: This study aimed to determine the percentage of EBV associated GC as well as to determine their clinicopathological characteristics. MATERIAL AND METHODS: The study included 80 patients with GC who were analysed for ethnicity, local growth of a tumour (T status), the presence of nodal metastases (N), the presence of distant metastases (M), stage of the disease and degree of carcinoma differentiation. For detection of EBV, immunostainings were performed on tumour tissue and the peripheral non-tumour gastric mucosa. RESULTS: Positive immunostaining with an antibody against EBV was found in 19 (23.75%) of the 80 patients with gastric carcinomas. EBV immunostainings were significantly different in patients with or without metastasis and between patients of Macedonian and Albanian ethnicity (p < 0.0001, p < 0.009, respectively). EBV immunoexpression was significantly associated with the presence of distant metastases and with patients of Albanian ethnicity. CONCLUSION: Association of EBV immunostainings with distant metastasis in patients with GC suggests the influence of EBV infection on the progression of gastric carcinoma. Due to scarce and doubtful literature data on EBV associated GC, further studies are necessary to determine the role of EBV regarding aetiology, treatment and prognosis in patients with EBV associated gastric carcinoma.

TP53 Mutation in Correlation to Immunohistochemical Expression of P53 Protein in Patients with Hepatocellular Carcinoma.

BACKGROUND: Mutations causing p53 inactivation are among the most common genetic alterations in human malignant tumours including hepatocellular carcinoma. Detection of p53 gene mutations in patients with hepatocellular carcinoma (HCC) should provide relevant data for the patients from the Republic of Macedonia and should allow the survivals additional therapeutic option as is gene therapy. AIM: We aimed to detect p53 gene mutations in HCC tissue, and to correlate them with the immunoexpression of p53 protein and multiple clinicopathologic characteristics of a tumour. MATERIAL AND METHODS: We analysed thirty patients with HCC for multiple clinic-pathological characteristics. Tumour tissue samples were immunostained for p53 and detection of p53 gene mutations was performed by polymerase chain reaction followed by Sanger sequencing. RESULTS: Changes in p53 gene sequence were detected in four patients (13.33%), one of them a polymorphism and the other three were missense point mutations with p53 immunoexpression of 50%, 0%, 0% and 90%, respectively. All patients with p53 mutations had cirrhosis. Two of them had Hepatitis B infection, moderately differentiated tumour and T2 status. There was one case with a well-differentiated tumour and one with T4 status. All of them were with vascular invasion. The size of the tumours was in the range of 2.5 cm to 16 cm. All 3 mutations were located in exon 7. CONCLUSION: Mutations in p53 gene are not always associated with obviously altered immunoexpression of p53 protein. Detection of p53 gene mutations is necessary in each case because the new therapeutic modalities offer to apply gene therapy.

HER2 Positive Gastric Carcinomas and Their Clinico-Pathological Characteristics.

BACKGROUND: HER2 protein expression in gastric carcinoma, in correlation with existing, acknowledged prognostic factors which include the parameters that determine the TNM stage of the disease, could become the basis for ongoing research in the field of molecular targeted and personalised therapy. AIM: To determine the expression of the HER2 protein in gastric carcinoma and to correlate the expression of a HER2 protein with clinicopathological characteristics of the disease. MATERIAL AND METHODS: The data of HER2 protein expression and the parameters of the TNM classification were obtained from the histopathological reports of the Institute of Pathology in Skopje, and for the clinical stage we used patient's files from the University Clinic for Abdominal Surgery in Skopje. RESULTS: The analysis of the correlation of HER2 protein expression and TNM classification parameters pointed out a significant correlation between HER2 protein expression and intragastric localisation of gastric carcinoma (P = 0.005), and the tumour grade of differentiation (P = 0.034). There was also a positive correlation between HER2 protein expression pattern and positive lymph nodes in patients with gastric carcinoma (P = 0.03). The expression pattern of HER2 +++ was significantly more common registered in patients with positive lymph nodes (P = 0.03). CONCLUSION: The expression of HER2 protein could represent a biological marker with prognostic and predictive value in patients with gastric carcinoma. Considering the high mortality rate in patients with gastric carcinoma and lack of international standardised therapeutic approach, research of the role and significance of HER2 overexpression and Trastuzumab therapy may prove useful in the development of new therapeutic strategies.

Tumour Lymphocytic Infiltration, Its Structure and Influence in Colorectal Cancer Progression.

BACKGROUND: The role of the immune system in the control of tumour progression has been stressed, recently. Many studies indicate the fact that the immune system can prevent tumour progression in several types of human malignant neoplasms including colorectal cancer. According to some authors, a higher density of "tumour-associated lymphocytes" (TAL), in malignant neoplasms, correlate with prolonged survival of patients. AIM: This study aims to determine the structure and the influence of the immune cells, TAL, in the progression of colorectal cancer (CRC). PATIENTS AND METHODS: The study included 103 patients with CRC operated at the University Clinic of Digestive Surgery in Skopje, whose operative material was analysed at the Institute of Pathology, Medical Faculty in Skopje. The structure of tumor-associated cells and their density were determined and were correlated with neoplasm's grade, local growth (T), positive lymph nodes, lymphatic invasion and stage of the disease. RESULTS: CD4+, CD8+ and CD20+ lymphocytes (Ly) were found in TAL. The density of TAL was significantly different in neoplasms with different T status, lymphatic invasion, patients with and without nodal metastasis and patients with a different stage of the disease. The density of CD4+, CD8+, and CD20+ cells were significantly different in neoplasms with different T. The density of CD8+ and CD20+ lymphocytes was lower in patients with nodal metastasis and higher stage. CONCLUSION: The density of tumor-associated lymphocytes can anticipate the disease progression in patients with colorectal cancer, and the density of TAL influences the control of tumour progression.

Endometrioid Adenocarcinoma Arising in Adenomyoma in a Woman with a Genital Prolapse - Case Report.

BACKGROUND: Endometrial cancer is the third-ranked genital malignancy in women and includes 3% of cancer deaths. There is a 2.8% chance of a woman developing endometrial cancer during her lifetime. Low-grade endometrioid adenocarcinomas are often seen along with endometrial hyperplasia, but high-grade endometrioid adenocarcinomas have more solid sheets of less-differentiated tumour cells, which are no longer organised into glands, often associated with surrounded atrophic endometrium. CASE REPORT: We present an unusual case of endometrial adenocarcinoma arising in adenomyoma in 74-year old woman presented with genital prolapse, without other clinical symptoms. Ultrasound evaluation revealed endometrium with 4 mm-thickness and atrophic ovaries. The cervical smear was normal. The patient underwent a total vaginal hysterectomy. The histopathology of the anterior uterine wall revealed an intramural adenomyoma of 4 mm in which some endometrial glands with malignant transformation of well-differentiated endometrioid adenocarcinoma without infiltration in surrounding myometrium and lymphovascular invasion were present. The endometrium lining the uterine cavity was predominantly atrophic, and only one focus of simplex and complex hyperplasia was found, with cell-atypia. According to AJCC/FIGO 2010, the tumour was classified: pTNM = pT1B pNX pMX G1 R0 L0 V0 NG1, Stage I. On dismiss, the near-future oncological consultation was recommended. CONCLUSION: We would like to point out the rare occurrence of such type of malignancy and the importance of meticulous histopathology evaluation, even after reconstructive surgery for genital prolapse.

Testicular adrenal rest tumors in boys with 21-hydroxylase deficiency, timely diagnosis and follow-up.

BACKGROUND: Testicular adrenal rest tumors (TARTs) are found in 30-94% of adult males with congenital adrenal hyperplasia (CAH). We sought to explore TART appearance through yearly ultrasound examination of testes in young boys with CAH, and its association with metabolic control and genetic mutations. METHODS: Twenty-five boys with 21-hydroxylase deficiency in the age group 4-18 years diagnosed during the period 2001-2016 were included in the study. ACTH, 17-hydroxyprogesterone, androstenedione and testosterone were measured at 4-month intervals. Growth and BMI were assessed at the time of evaluation. PCR/ACRS method was used for CYP21A2 gene analysis. Testicular ultrasound examination was performed yearly. RESULTS: TARTs were detected by ultrasound in 8 children at the age of 6-16 years (13.2 years average). Five had salt-wasting form, two had simple virilizing form and one had non-classic form of CAH. Significant differences in the17OHP and androstenedione levels were detected between the boys, adherent and non-adherent to therapy. Inadequate metabolic control was not different in boys with and without TART (11/17 and 5/8 respectively). No significant difference was detected in the distribution of genetic mutations or adherence to therapy between patients with and without TARTs. One patient had a mutation not reported thus far in TART and another developed leukemia. CONCLUSION: TART is not rare in young boys with CAH, irrespective of the specific mutation or metabolic control. Ultrasound screening helps timely diagnosis and adjustment of therapy.

Standardization and optimization of fluorescence in situ hybridization (FISH) for HER-2 assessment in breast cancer: A single center experience.

Accurate assessment of human epidermal growth factor receptor 2 (HER-2) is crucial in selecting patients for targeted therapy. Commonly used methods for HER-2 testing are immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Here we presented the implementation, optimization and standardization of two FISH protocols using breast cancer samples and assessed the impact of pre-analytical and analytical factors on HER-2 testing. Formalin fixed paraffin embedded (FFPE) tissue samples from 70 breast cancer patients were tested for HER-2 using PathVysion™ HER-2 DNA Probe Kit and two different paraffin pretreatment kits, Vysis/Abbott Paraffin Pretreatment Reagent Kit (40 samples) and DAKO Histology FISH Accessory Kit (30 samples). The concordance between FISH and IHC results was determined. Pre-analytical and analytical factors (i.e., fixation, baking, digestion, and post-hybridization washing) affected the efficiency and quality of hybridization. The overall hybridization success in our study was 98.6% (69/70); the failure rate was 1.4%. The DAKO pretreatment kit was more time-efficient and resulted in more uniform signals that were easier to interpret, compared to the Vysis/Abbott kit. The overall concordance between IHC and FISH was 84.06%, kappa coefficient 0.5976 (p < 0.0001). The greatest discordance (82%) between IHC and FISH was observed in IHC 2+ group. A standardized FISH protocol for HER-2 assessment, with high hybridization efficiency, is necessary due to variability in tissue processing and individual tissue characteristics. Differences in the pre-analytical and analytical steps can affect the hybridization quality and efficiency. The use of DAKO pretreatment kit is time-saving and cost-effective.

Immunohistochemical Expression of Epidermal Growth Factor Receptor in Hepatocellular Carcinoma.

INTRODUCTION: Epidermal growth factor receptor (EGFR) signaling plays an important role in various cancers, including hepatocellular carcinoma (HCC). We aimed to evaluate immunoexpression of EGFR in HCC and surrounding non-tumor liver tissue and to correlate it to multiple clinicopathologic data. MATERIAL AND METHODS: We analyzed 60 patients with HCC for multiple clinicopathologic characteristics and survival. Presence of the immunosignal and the percentage of positive tumor cells at the whole tumor tissue sample and adjacent cirrhotic liver tissue were semi-quantitatively determined. RESULTS: Nineteen patients (31.67%) were female and 41 (68.33%) were male ranging in age from 31 to 85 years, median 61.88±10.51. Mean survival time for female patients was 8.86±1.76 months, for male 13.03±1.50 months and overall survival was 11.6051±1.19 months. The most patients had: T2 status (41.67%), no enlarged lymph nodes (90%), vascular invasion (63.33%) and well differentiated (43.33%) tumors. EGFR immunoexpression was determined in range from 0% to 100% in both tumor and non-tumor tissue with mean value of 39.58% in tumor and 86.86% in cirrhotic tissue (p<0.00). Higher percent of tumor EGFR positive cells were found in cases with higher T status, higher levels of AFP and poorly differentiated carcinoma, but not significantly. Lower percent of tumor EGFR positive cells were found in patients with vascular invasion and enlarged lymph nodes, but also not significantly. EGFR expression in tumor tissue significantly influenced survival of the patients (p<0.05). CONCLUSION: The study showed that expression of EGFR in lower percentage of tumor cells was associated to favorable prognosis, making it a potential prognostic marker and therapeutic target.

Androgen Receptor Expression in Epithelial and Stromal Cells of Prostatic Carcinoma and Benign Prostatic Hyperplasia.

BACKGROUND: Prostatic carcinoma (PCa) derives from prostatic epithelial cells. However stromal microenvironment, associated with malignant epithelium, also plays a role in prostatic carcinogenesis. Alterations in prostatic stromal cells contribute to the loss of growth control in epithelial cells that lead to progression of PCa. AIM: To analyse the differences between Androgen Receptor (AR) expression in both epithelial and stromal cells in PCa and the surrounding benign prostatic hyperplasia (BPH) and to compare the results with tumour grade. MATERIAL AND METHODS: Samples from 70 cases of radical prostatectomy specimens were used. The expression and intensity of the signal for AR was analysed in the epithelial and stromal cells of PCa and BPH, and the data was quantified using histological score (H-score). RESULTS: AR showed significantly lower expression in both epithelial and stromal cells of PCa compared to BPH. In PCa a significant positive correlation of AR expression was found between stromal and epithelial cells of PCa. AR expression showed a correlation between the stromal cells of PCa and tumour grade. CONCLUSION: AR expression is reduced in epithelial and stromal cells of PCa. Expression of AR in stromal cells of PCa significantly correlates with tumour grade.

Correlation Between Microvessel Density and Morphological Features in Skin Squamous Cell Carcinoma.

INTRODUCTION: Abnormal angiogenesis is described in tumor growth and it facilitates its metastatic spread. Tumors with high angiogenic activity belong to the category of aggressive tumors with poor prognosis for patients. The aim of this study was to determine the blood vessels density (BVD), i.e. neovascularization at the tumor invasive front in skin squamous cell carcinoma (SCC) in order to determine its possible role in the tumor progression, and to correlate it to the blood vessels density of healthy skin and with the prognostic parameters of the TNM classification: T status, depth of tumor invasion (DI) and tumor histological grade (G), which were also correlated between each other. MATERIAL AND METHODS: The material consisted of surgical specimens obtained from 30 patients with skin SCC, who underwent surgery. Tissue samples were routinely processed by standard paraffin technique stained by Hematoxilin-Eosin and immunohistochemically with antibodies against smooth muscle actin (SMA) and CD34. The BVD in the invasive front of the neoplasms was correlated to the healthy skin, tumor status (pT), depth of invasion and grade of histological differentiation (pG). RESULTS: The histological analysis has shown a high statistical difference in the density of blood vessels in SCC compared to the healthy skin and statistical difference in BVD in neoplasms with different depth of invasion and different grade of differentiation. The density of neovascularzation increased with the deeper invasion and the worse differentiation. CONCLUSION: The increased vascularization at the invasive front of SCC with deeper invasion and worse differentiation has pointed out to its possible role in neoplasm progression.

Overexpression of UHRF1 gene correlates with the major clinicopathological parameters in urinary bladder cancer

ABSTRACT Introduction Recently, expression of the UHRF1 gene was found to be up-regulated in numerous neoplasms, including the urinary bladder transitional cell carcinoma (TCC). Objective The aim of our study was to determine if the expression levels of UHRF1 gene correlates with the major pathological characteristics of the tumor and patients’ clinical outcome. Materials and Methods In our study, we have analyzed the tissue samples derived from group of 70 patients with histologically confirmed TCC of the urinary bladder, while normal urinary bladder mucosa obtained from 40 patients with nonmalignant diseases was used as a negative control group. Expression of UHRF1 gene in each patient sample was determined using reverse transcriptase-polymerase chain reaction. Results UHRF1 gene expression was found to be app. 2.5 times higher in samples from patients with TCC in comparison with normal epithelium derived from control group patients. Analysis show that gene expression correlates with the malignancy of the tumor. A highly significant differences were found between the expression values of samples from low and high grade TCC, as well as between the high grade and control group. UHRF1 expression was higher in patients with non-muscle invasive disease than in those with muscle invasive disease. Conclusions The result of this study indicates that UHRF1 gene expression levels correlates with the major pathological characteristics of TCC samples and with the clinical outcome of those patients. Determination of UHRF1 gene expression could have a potential to be used as a sensitive molecular marker in patients with urinary bladder cancer.