Yurdanur Sullu

Matrix metalloproteinase-2 (MMP-2) and MMP-9 expression in invasive ductal carcinoma of the breast

Matrix metalloproteinase-2 (MMP-2) and MMP-9 are gelatinases that play a role in the invasion and metastasis of cancer through the destruction of the basal membrane and extracellular matrix. In this study, we investigated the immunohistochemical expression of MMP-2 and MMP-9 and the correlation between the expression levels and prognostic clinicopathological parameters in 140 patients with invasive ductal carcinoma (IDC). The staining scores for MMP-9 were negative in 21 cases (15%), mild in 27 cases (19%), and strong in 92 cases (66%). MMP-9 expression was increased in high-grade (p=0.001), triple-negative (ER, PR, HER2 negative) (p=0.006), and ER-negative tumors (p=0.004) and tumors with distant metastases (p=0.028). MMP-9 expression was increased in cases with HER2 over-expression/amplification, but no statistically significant difference was found (p=0.215). No correlation was found between lymph node metastasis or tumor size and MMP-9 expression (p=0.492 and p=0.448, respectively). The staining scores for MMP-2 in 140 cases were negative in 10 cases (7%), mild in 25 cases (18%), and strong in 105 cases (75%). MMP-2 expression was increased in ER-negative and high-grade tumors in the lymph node-negative group (p=0.025 and 0.026, respectively). High MMP-9 expression was associated with a shorter disease-free survival and overall survival times (p=0.042 and p=0.046, respectively). In conclusion, increased MMP-9 expression is related to poor prognostic clinicopathological factors in IDC, and hence, it can be utilized as a supplementary prognostic marker. The role of MMP-2 expression in the prognosis of IDC is rather limited.

Expression of Plakophilins (PKP1, PKP2, and PKP3) in Gastric Cancers

BackgroundThe importance of cell-cell junction proteins (including armadillo proteins) in tumor biology is known, but limited with regard to plakophilins. We explored the relationship between plakophilins (PKP1, PKP2, PKP3) to gastric cancer via immunohistochemical techniques.MethodsWe compared the immunohistochemistry of PKPs in 34 gastric adenocarcinomas and 20 normal gastric tissues.ResultsIn gastric cancer, PKP1 expression was unchanged but PKP2 and PKP3 were significantly decreased as compared to normal controls. There was no observable clinical association with PKP1 or PKP2 expression; however, low PKP3 level and poor prognosis appeared to correlate with regards to node number and tumor stage. The mean disease-free survival (DFS) was 38 ± 3 months (range: 32 - 44) and mean overall survival (OS) 42 ± 4 months (range: 38 - 50). Decreased PKP2 appeared to negatively impact DFS.ConclusionDecreased PKP2 and PKP3 may be early prognostic markers and loss of PKP3 expression during gastric carcinoma progression may indicate an invasive phenotype.

Vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and thrombospondin-1 (TSP-1) expression in urothelial carcinomas

Angiogenesis is a multistep process that depends on the balance of proangiogenic factors and inhibitors as well as on interactions with the extracellular matrix. We examined the immunohistochemical expression of the defining angiogenic agents, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9), and the antiangiogenic agent thrombospondin-1 (TSP-1) in 131 patients with urothelial carcinoma and correlated their expression levels with clinicopathological parameters. VEGF and MMP-9 expression was higher in high-grade tumors than in low-grade tumors (p=0.000 and p=0.001, respectively), whereas the reverse was true for TSP-1 (p=0.000). VEGF and MMP-9 expression was higher in deeper tumors compared to superficial tumors and in invasive tumors compared to non-invasive tumors (p=0.001 and p=0.001, respectively), while TSP-1 was lower (p=0.000). We could differentiate 22 of 41 muscle-invasive (T2) cases as superficial (T2a; n=7) or deep (T2b; n=15), but no difference was found between them regarding VEGF, MMP-9, or TSP-1 expression (p=0.783, p=0.289, and p=0.783, respectively). There was a positive correlation between VEGF and MMP-9 expression (p=0.008, r=0.23) but a negative correlation between MMP-9 and TSP-1 expression (p=0.014, r=-0.21). Increased VEGF and MMP-9 expression as well as decreased TSP-1 expression may play considerable roles in the invasion and differentiation of urothelial carcinoma.

Poor prognostic clinicopathologic features correlate with VEGF expression but not with PTEN expression in squamous cell carcinoma of the larynx

BackgroundThe aim of this study was to assess the relationship between expression of vascular endothelial growth factor (VEGF) and phosphatase and tensin homolog deleted in chromosome ten (PTEN), angiogenesis and clinicopathological parameters of squamous cell carcinoma of the larynx.MethodsWe examined immunohistochemical expression of VEGF and PTEN and CD34 for microvessel density (MVD) in sections of formalin-fixed, paraffin embedded tissue blocks of 140 patients with squamous cell carcinoma of the larynx. The intensity of VEGF and PTEN staining and the proportion of cells staining were scored.ResultsThe tumor grade was not significantly related to PTEN expression, but it was to VEGF expression (p = 0.400; p = 0.015, respectively). While there was no significant relationship between PTEN expression and tumor size and cartilage invasion (p = 0.311, p = 0.128), there was a significant relationship between the severity of VEGF expression and tumor size (p = 0.006) and lymph node metastasis (p = 0.048) but not cartilage invasion (p = 0.129). MVD was significantly higher in high-grade tumors (p = 0.003) but had no significant relationship between MVD, lymph node metastasis, and cartilage invasion (p = 0.815, p = 0.204). There was also no significant relationship between PTEN and VEGF expression (p = 0.161) and between PTEN and VEGF expression and the MVD (p = 0.120 and p = 0.175, respectively).ConclusionsIncreased VEGF expression may play an important role in the outcome of squamous cell carcinoma of the larynx. PTEN expression was not related to VEGF expression and clinicopathological features of squamous cell carcinoma of the larynx.

SOX4 expression levels in urothelial bladder carcinoma

High levels of SOX4 gene expression have been reported in a variety of human cancers. The protein may function in the apoptosis pathway, leading to cell death as well as to tumorigenesis. The aim of this study was to investigate the levels of SOX4 expression in bladder cancer. Urinary bladder tumor samples were obtained from 57 bladder cancer and 13 normal bladder biopsies. The levels of SOX4 expression in bladder cancer were determined by immunohistochemistry and real-time PCR. SOX4 gene expression was increased 2.2 times in bladder tumors as compared with normal tissue. The presence of protein was confirmed by immunostaining. There were significant differences between immunostaining of bladder tumors and normal bladder tissue (P=0.001). The present data suggest that SOX4 gene may have a role in bladder cancer tumorigenesis.

Two cases of fetus in fetu

Fetus in fetu (FIF) is a rare cause of abdominal mass in children. One of the malformed monozygotic diamniotic twins is located in the body of other twin. It is differentiated from teratoma by the presence of vertebral organization with limb buds and other organ systems. Diagnosis is based on radiologic findings. Surgical excision is the treatment of choice, leading to the complete removal of the mass. To our knowledge, less than 200 cases have been described in the literature. Herein, we report 2 cases of FIF, a newborn who was diagnosed antenatally and a three-and-half-year- old boy diagnosed with mediastinal FIF after admission for recurrent respiratory tract infections.

A case of acetaminophen (paracetamol) causing renal failure without liver damage in a child and review of literature

Acetaminophen (paracetamol) is a widely used drug and known as a safety antipyretic and analgesic drug in childhood. Acetaminophen-associated liver damage is more recognized than kidney damage. Nephrotoxicity and hepatotoxicity can be seen together after acetaminophen overdose, but renal damage without liver damage is a rarely seen entity in all age groups being reported more rarely in childhood. We present here a 16-year-old girl with renal failure without liver damage because of acetaminophen toxicity and a review of literature for pathophysiological mechanisms, clinical course, treatment, and outcome.

A case of tuberculous peritonitis in childhood.

Currently, tuberculosis remains a major public health problem worldwide. Peritoneal tuberculosis occurs in approximately 1% of all of tuberculosis cases and is rarely observed in children. Diagnosis and treatment delays caused by mimicking many other intra-abdominal diseases can lead to increases in morbidity and mortality. Here, we present a case of a four-year-old child with tuberculosis peritonitis who was diagnosed by laparoscopic biopsy and histopathological examination and recovered with antituberculosis therapy. Peritoneal tuberculosis should be considered in younger patients and adults with fever, abdominal pain and weight loss in endemic areas.

Bcl-2 Expression in Skin Pathergy Reaction of Behçet’s Disease

Background: Bcl-2 expression in leukocytes plays an important role in autoimmune and inflammatory disease. Objective: In the present study, we investigated the Bcl-2 expression in the skin pathergy reaction (SPR) of Behçet’s disease (BD). Methods: The skin pathergy test (SPT) was performed on 23 patients with BD and 7 healthy controls. After 48 h, SPT specimens were taken by punch biopsy. Control samples were also obtained from the normal skin of 7 patients with BD and 11 patients with BD-unrelated leukocytoclastic vasculitis. Biopsy specimens were evaluated by routine histopathological examination and immunohistochemical Bcl-2 staining. Results: The SPT was clinically positive in 9 of 23 patients and histopathologically positive in 13 but never in the healthy controls. The majority of leukocytes in 12 of 13 histopathologically positive specimens were stained with Bcl-2. Only 3 BD-unrelated leukocytoclastic vasculitis samples showed Bcl-2 positivity. No Bcl-2 staining was found in healthy controls and normal skin samples of patients with BD. Conclusion: Our data may suggest a role of Bcl-2-mediated inflammation in the pathogenesis of the SPR in BD.

Male Breast Cancer: 20 Years Experience of a Tertiary Hospital from the Middle Black Sea Region of Turkey

BACKGROUND Male breast cancer is a rare neoplasm, and its treatments are based on those of female breast cancer. This study aimed to analyze 20 years of male breast cancer clinical characteristics and treatment results from the Middle Black Sea Region of Turkey. MATERIALS AND METHODS A retrospective analysis of 16 male breast cancer patients treated in our tertiary hospital between 1994 and 2014 was performed. Epidemiologic data, tumor characteristics, and treatments were recorded and compared with 466 female breast cancer ((premenopausal; n=230)+(postmenopausal n=236)) patients. The 5-year disease-free and overall survival rates were calculated. RESULTS Male breast cancer constituted 0.1% of all malignant neoplasms in both sexes, 0.2% of all malignant neoplasms in males, and 0.7% of all breast cancers. The mean patient age in this study was 59.8±9.5 (39-74) years. The mean time between first symptom and diagnosis was 32.4±5.3 (3-60) months. Histology revealed infiltrative ductal carcinoma in 81.3% of patients. The most common detected molecular subtype was luminal A, in 12 (75%) patients. Estrogen receptor rate (93.8%) in male breast cancer patients was significantly higher than that in female breast cancer (70.8% in all females, p=0.003; 68.2% in postmenopausal females, p=0.002) patients. Most of the tumors (56.3%) were grade 2. Tumor stage was T4 in 50% of males. The majority (56.3%) of the patients were stage III at diagnosis. Surgery, chemotherapy, radiotherapy and endocrine-therapy were applied to 62.5%, 62.5%, 81.2% and 73.3%, respectively. Loco-regional failure did not occur in any of the cases. All recurrences were metastastic. The 5-year disease-free and overall survival rates in male breast cancer patients were 58% and 68%, respectively. CONCLUSIONS Tumors found in male breast cancer patients were similar in size to tumors found in females, but they advanced to T4 stage more rapidly because of the lack of breast parenchymal tissues. The rate of estrogen receptor expression tended to be higher in male breast cancer patients than in female breast cancer patients. Metastasis is the most important problem in initially non-metastatic male breast cancer patients.