Expression of Stromal Caveolin- 1 May Be a Predictor for Aggressive Behaviour of Breast Cancer.

Caveolin-1 (Cav-1) is well known as a principal scaffolding protein of caveolae which are specialized plasma membrane structures. The role of Cav-1 in tumorigenesis of breast cancers is relatively less studied. The aim of the present study is to describe the biological roles of Cav-1 in breast cancers considering its contrasting dual functions as an oncogene and as a tumor suppressor. This study included 71 females with breast cancer who had been histopathologically diagnosed in Private Gunes Pathology Laboratory between the years 2007, and 2012. The mean age is 52.48 ± 12.8 years. Patients were followed up for a mean period of 47.97 ± 20.48 months. We didn't determine Cav-1 positive tumor cells. In 36 cases (50.7%), there were stromal expressions of Cav-1. In the statistical analysis, there was a statistically significant correlation between Cav-1 expression and ER (p = 0.033), metastasis (p = 0.005), lymphatic invasion (p = 0.000), nodal metastasis (p = 0,003), perinodal invasion (p = 0.003), metastasis (p = 0.005) and survival (p = 0.009). We found that Cav-1 expression is associated with tumor size, histological grade, lymph node involvement. Accordingly, we have suggested that Cav-1 may be a predictive biomarker for breast cancer.

The role of p95HER2 in trastuzumab resistance in breast cancer.

PURPOSE: Trastuzumab, the HER2 oncogene targeting drug, shows remarkable clinical efficacy in HER2-amplified breast cancer patients. Despite of robust activity, some of the patients with HER2-positive breast cancers do not get the benefit due to trastuzumab resistance. Overexpression of p95HER2 is one of the molecular mechanisms of trastuzumab resistance. The purpose of this study was to investigate whether p95HER2 overexpressing breast cancers were resistant to trastuzumab. METHODS: p95HER2 (truncated HER2) and HER2 were determined by real-time polymerase chain reaction (RT-PCR) analysis. HER2 protein expression and HER2 gene amplification were also determined by immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH). Archival material from 80 formalin-fixed paraffin-embedded (FFPE) breast cancer tumor tissues was used for the study. None of the cases had metastases at the initial diagnosis. HER2-positive cases were treated with trastuzumab with/without chemotherapy. RESULTS: Of 80 breast cancer cases 39 (48.7%) were HER2-positive and had trastuzumab treatment. Of these 39 cases 11 (28.2%) were trastuzumab-resistant and 28 (71.8%) were not, 17 (43.6%) were recurrent cases and 22 (56.4%) were not. Three patients died during follow-up. p95HER2 mean ratio was 11.01±19.73 in 11 cases which were trastuzumab-resistant, while p95HER2 mean ratio was 1.99±1.37 in 28 cases without trastuzumab resistance. If p95HER2 ratio was low, there was no trastuzumab resistance. However, when p95HER2 ratio was high, there was trastuzumab resistance (p=0.210, Mann-Whitney U test). CONCLUSION: p95HER2 was correlated with trastuzumab resistance, but it was not an independent factor of trastuzumab resistance. We claim that p95HER2 is sensitive but not specific for the prediction of trastuzumab resistance.

Acute coronary syndrome in two patients with mechanical valve prostheses.

We report 2 similar cases of embolic myocardial infarction due to thrombus on a mechanical prosthesis despite anticoagulation therapy. In our first case, aspiration of the thrombus was performed successfully. Our second patient was given medical treatment with target international normalized ratio values between 3.5 and 4.0.

Value of expression of insulin-like growth factor-1 receptor in gastric adenocarcinomas and normal gastric tissues.

BACKGROUND/AIMS: Insulin-like growth factor-1 receptor (IGF-1R) plays critical roles in cell proliferation, differentiation, apoptosis, and transformation. Suppression of IGF-1R by means of antisense methods and specific antibodies causes cell apoptosis and growth inhibition of cancer cells. The present study aims to investigate whether there is a difference between normal and cancerous tissue with respect to IGF-1R expression and to assess the relationship between IGF-1R expression and tumor stage, degree of differentiation, and lymph node metastasis by examining IGF-1R expression in cancerous and normal tissues of gastric adenocarcinoma cases of different stages. MATERIALS AND METHODS: By using immunohistochemical methods, IGF-1Rb (H-60) (1/100, Santa Cruz Biotechnology, SC-9038, Texas,USA) expression was investigated in paraffin-embedded blocks obtained from total/partial gastrectomy material pertaining to 47 gastric adenocarcinoma cases. IGF-1R expression was evaluated semi-quantitatively in terms of intensity and distribution in both normal and cancerous tissues. RESULTS: Insulin-like growth factor-1 receptor expression mean score was 5.38 and 8.40 for cancerous and for normal gastric tissues, respectively. IGF-1R expression decreased significantly in cancerous tissues compared normal tissue (p:0.001). When all cases with and without lymph node metastasis were analyzed, IGF-1R expression was observed to decrease for cases with lymph node metastasis compared to those without lymph node metastasis (p:0.035). CONCLUSION: Insulin-like growth factor-1 receptor expression in gastric cancer tissue has proven to be considerably lower than IGF-1R expression in normal gastric mucosa. Metastatic progression reduces IGF-1R expression gradually in cancer tissue.

Regulatory T cells and their prognostic value in hepatopancreatobiliary tumours.

BACKGROUND/AIMS: The aim of this study was to determine the prognostic values of Foxp3+ Treg cells, CD4+ Tcells and CD8+ T cells in cancer cases of gallbladder, pancreas and liver. METHODOLOGY: This study included 20 patients with gallbladder cancer, 25 patients with pancreatic cancer and 8 patients with liver cancer. Foxp3, CD4 and CD8 were immunohistochemically evaluated and compared with histopathological and clinical prognostic parameters. RESULTS: Foxp3, CD4 and CD8 expression levels were significantly higher in peritumoral areas than in intratumoral areas in patients with gallbladder, pancreas, liver cancers (p<0,05). Positivity of Foxp3, CD4 and CD8 was correlated with advanced stage (p<0,05), poor differentiation, lymphovascular invasion, perineural invasion, advanced age. Patients with high positivity of Foxp3 had a shorter disease free survival (p<0,05). CONCLUSION: Our results indicate that the ratio of Tregs/T helper cells (Foxp3+/CD4+) cells was higher in intratumoral area in hepatopancreatobiliary tumors. We conclude that intratumoral inlamatory cells might work for cancer cells, besides peritumoral cells work against cancer cells.

Carnitine protects the intestine against reperfusion injury in rats.

BACKGROUND: Although the negative effects of ischemia on anastomotic healing have been shown in many studies, there is no adequate information on the effects of reperfusion injury. Therefore, in this study, we investigated the effect of ischemia-reperfusion (IR) injury on intestinal anastomosis and the protective efficiency of carnitine in an experimental relatively short intestinal ischemia and long duration reperfusion model. METHODS: Animals were divided into three groups (n=14). Each group was separated into two subgroups. In subgroups A, morphologic injury and the number of perfused intestinal muscular microvessels were analyzed to show "no-reflow phenomenon." Intestinal resection and anastomosis were performed in subgroups B. Carnitine group (IRCarG) received 200 mg/kg intravenous carnitine 2 min prior to reperfusion. Malonyldialdehyde, nitric oxide levels in tissue and blood, collagen levels, bursting pressures, and histopathologic evaluation of anastomosis were measured in subgroups B. RESULTS: Morphologic damage was statistically lower, number of perfused microvessels and epithelial regeneration were statistically higher in IRCarG, compared with ischemia-reperfusion group (P=0.03, P=0.008, P=0.05, respectively). CONCLUSION: Carnitine application prior to reperfusion may reduce the severity of the reperfusion injury by preventing the occurrence of no-reflow phenomenon, increase the number of perfused microvessels in the ischemic intestine, and may improve epithelial regeneration in intestinal anastomosis.

Angiomyxoma: a rare tumor of the umbilical cord.

Tumors of the umbilical cord are rare anomalies and should be considered when using prenatal ultrasound for detection of cystic lesions. Differential diagnosis of umbilical cord tumors should comprise umbilical cord teratoma, hemangioma and angiomyxoma. It can also be an umbilical cord polyp, umbilical cord cyst, hernia into the cord and omphalocele, which are mostly isolated findings, except omphalocele. Angiomyxoma is a rare tumor of the umbilical cord and is associated with incresaed perinatal morbidity and mortality. We present a 22-year-old woman with a large umbilical cord tumor who underwent a caesarean section. As in our case, neither chromosomal aberrations nor elevated alphafetoprotein were found after amniocentesis or chordocentesis. Macroscopical and microscopical pathological examinations of the mass after delivery revealed an angiomyxoma with cystic degenerations in myxoid stroma.

Total removal of cervicothoracic intramedullary 160-mm-long spinal cord ependymoma: a rare case report.

Ependymomas are neuroectodermal tumours arising from ependymal cells of the ventricular system, choroid plexus, filum terminale, or central canal of the spinal cord. We report on a 160-mm-long cervicothoracic intramedullary spinal cord ependymoma. The tumour was totally removed; no radiotherapy was used as an adjunctive therapy. Postoperative magnetic resonance imaging confirmed that the tumour had been totally removed.

Primary cardiac angiosarcoma with right coronary-to-right atrium fistula.

Primary tumours of the heart are rare. About 25% of all cardiac tumours are malignant and the most common of these is the angiosarcoma. We present a 61-year-old male with a right atrial angiosarcoma that was detected on coronary angiography. The tumour showed marked vascularity and a right coronary-to-right atrium fistula, and the patient underwent surgical resection. Pathological examination of the tumour was consistent with a cardiac angiosacoma and the diagnosis was also confirmed by immuno-histochemistry. He consequently underwent chemotherapy, however the patient died 60 days after the surgery.

Phyllodes tumor of the breast in an adolescent girl.

Phyllodes tumor (PT) is an uncommon tumor in adolescent girls and young women. A case of PT in a 14-year-old girl is reported. The clinical examination showed a painless tumor that had grown during 10 months. Total excision of the mass with wide margin was performed. The diagnosis, behavior, and treatment of this rare tumor are discussed.

Intravitreal triamcinolone acetonide injection in CRVO associated with Wegener's granulomatosis.

A 33-year-old man developed unilateral non-ischemic central retinal vein occlusion associated with systemic Wegener's granulomatosis. Four milligrams of triamcinolone acetonide was injected intravitreally twice 6 months apart in conjunction with ongoing systemic immunosuppressive therapy. No change was made in the systemic immunosuppressive regimen. Wegener's granulomatosis should be considered in the differential diagnosis of central retinal vein occlusion in the young age group and intravitreal triamcinolone acetonide is a good adjunct to systemic immunosuppressive therapy that eliminates the need for modifying the systemic treatment regimen.

Matrix metalloproteinase-9,-3 and tissue inhibitor of matrix metalloproteinase-1 in colorectal cancer: relationship to clinicopathological variables.

The balance between matrix metalloproteinases (MMPs) and their physiological tissue inhibitors of matrix metalloproteinases (TIMPs) is crucial in tumour invasion and progression. The aim of this study was to investigate the levels of MMP-9, MMP-3 and TIMP-1 in colorectal cancer (CRC) and to evaluate these proteinases and their inhibitor with respect to clinicopathological variables. Activities of pro- and active MMP-9 were measured in paired tumour and distant normal tissue specimens from 43 patients with CRC using gelatin zymography. ELISA was employed for the determination of MMP-9, MMP-3 and TIMP-1 protein expressions. The activity levels of pro- and active MMP-9 and protein expression levels of MMP-9, MMP-3 and TIMP-1 were higher in tumour tissues than in the corresponding normal tissues; the differences being significant for all (p < 0.05), except TIMP-1. Similarly, active MMP-9/proMMP-9 and the ratio of protein expression level of MMP-9-TIMP-1 were found to be significantly higher in tumour tissues ( p < 0.01). Among all the clinicopathological variables investigated, significant correlations were found between MMP-9 and presence of perineural invasion, MMP-3 and lymph node status, TIMP-1 and tumour differentiation, MMP-9/TIMP-1 ratio and histological types ( p < 0.05). In conclusion, MMP-3 was not as notably increased as MMP-9 in tumour tissues. However, different roles may be attributed to MMP-9 and MMP-3 in CRC development and progression. Additionally, assessment of TIMP-1 in relation to MMPs appeared to be crucial in CRC studies to provide a basis for the re-evaluation of the clinical usefulness of TIMP-1 in colorectal cancer.

Crohn's colitis perforation due to superimposed invasive amebic colitis: a case report.

The clinical and microscopic appearances of inflammatory bowel disease may be very similar to those of amebic colitis. The coexistence of invasive amebiasis with inflammatory bowel disease may have disastrous results. Patients with inflammatory bowel disease have a greater prevalence of amebiasis, but this association is more significant for ulcerative colitis. There have been very few reports in the literature presenting the superimposition of amebiasis on Crohn's disease. In this report, a rare case of Crohn's colitis with superimposed amebiasis resulting in colonic perforation is presented. Patients with inflammatory bowel disease traveling to endemic areas may benefit from receiving a course of prophylactic anti-amebic medication.

PS2 and HSP70 expression in rectal adenocarcinomas: an immunohistochemical investigation of 45 cases.

OBJECTIVE: To evaluate the expression of HSP70 and pS2 and to determine whether it may be an additional prognostic variable in the prediction of recurrence and survival in rectal adenocarcinomas. METHODS: The paraffin sections of 45 patients with rectal carcinoma who were treated with surgical resection were stained with HSP70 and pS2 antibodies by using the standard biotin immunoperoxidase method. Cytoplasmic staining for both antibodies was scored semiquantitatively. RESULTS: Only 16 (35.6%) tumors showed a positive cytoplasmic reaction with HSP70 antibody, while pS2 expression was observed in 26 (57.8%) tumors. There was an association between HSP70 and pS2 expression (P=0.002). No correlations were found between HSP70 and pS2 expression and tumor recurrence or overall survival and other prognostic factors. However, the type of surgical resection was significantly associated with pS2 expression status (P=0.013). Significant correlations were detected between tumor recurrence and other clinicopathologic parameters, such as clinical stage, lymph node involvement, and resection type (P=0.015, P=0.015, and P=0.03, respectively). Resection type was significantly associated with clinical outcome, recurrence, and metastasis (P=0.009, P=0.03, P<0.01, respectively). In addition, there was a statistically significant relationship between clinical stage and final outcome (P=0.005). CONCLUSIONS: The strong correlation between pS2 expression and incomplete surgical resection suggests that pS2 may be related to invasive tumor behavior and may also play a role in tumor recurrence, although this latter association did not reach statistical significance in this study. HSP70 expression does not appear to be related to tumor invasiveness or tumor recurrence.

Is rectal washout necessary in anterior resection for rectal cancer? A prospective clinical study.

BACKGROUND: Implantation of exfoliated malignant cells has been suggested as a possible mechanism of tumor recurrence in colorectal anastomoses that might be prevented by cytocidal washout. The aim of our study was to assess whether malignant cells are likely to be collected by a circular stapler introduced transanally to perform an anastomosis and to observe local recurrences during follow-up, with special attention to the washout status of patients. METHODS: Between May 1999 and March 2004, 96 patients with carcinoma of the rectum and distal sigmoid colon undergoing anterior resection under the care of three surgeons (only one of whom routinely performed rectal washout) were prospectively studied. While 38 patients had rectal washout with 5% povidone-iodine before anastomosis, 58 patients did not. A circular stapler was used for anastomosis, and the stapler was immediately rinsed in 100 ml of saline. The fluid was then classified as "acellular," "malignant cells identified," or "benign cells identified" by pathologists. RESULTS: Malignant cells were collected from the circular stapler after use in 3 patients (8%) on whom rectal washout was performed and in 2 (3%) patients who did not have rectal washout performed (P=0.631). Three patients (8%) in the washout group developed local recurrence, and 2 patients (3.4%) in the no-washout group had local recurrence (one was anastomotic recurrence) (P=0.338). The median follow-up time was 23 (range: 9-70) months. CONCLUSIONS: There were no differences in terms of the number of patients who had malignant cells collected from the circular stapler and local recurrence rates between the two groups. Although this is not a randomized study and size and mean follow-up time of the study were not sufficient, our results did not offer rational arguments in support of intraoperative rectal washout when a circular stapler is used after low anterior resection for carcinoma. Because of the limitations of our study, however, we are unable to arrive at a definite conclusion regarding rectal washout. There is a need for a randomized, controlled, large-scale, multicenter trial to establish the clinical relevance of intraoperative rectal washout.

Is there a possible relation between atrophic gastritis and premature atherosclerosis?

BACKGROUND: In this study, we have aimed to show the possible relation between atrophic gastritis and premature atherosclerosis via hyperhomocysteinemia. MATERIALS AND METHODS: Thirty-four patients with atrophic gastritis were enrolled to the study. The control group consisted of 35 patients with non-atrophic gastritis. Classical cardiovascular disease risk factors did not significantly differ between atrophic gastritis and control subjects. The presence and degree of atrophic gastritis were assessed histologically and Helicobacter pylori infection was determined by both histologic and serologic methods. Body mass index was measured by standard technique blood fasting glucose, serum creatinine, total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, vitamin B12, folic acid, and homocysteine levels were measured by biochemical methods. Carotid intima-media thickness was measured by B-mode ultrasonography to examine the premature atherosclerosis. RESULTS: Plasma vitamin B12 levels were significantly lower (p = .00) and homocysteine levels were significantly higher (p = .01) in the atrophic gastritis group. There was no statistically significant difference in plasma folic acid levels between the two groups (p = .728). Carotid intima-media thickness was higher in the atrophic gastritis group than in the control group (0.516 mm versus 0.465 mm), but this difference did not show any statistical significance (p = .062). CONCLUSION: Our results showed that atrophic gastritis may cause hyperhomocysteinemia, which is an independent risk factor for atherosclerosis and cardiovascular diseases. However, when compared with controls, carotid intima-media thickness of the atrophic gastritis patients was found to be higher but did not reach statistically significant levels.

The clinical significance of p53, p21, and p27 expressions in rectal carcinoma.

Many checkpoint proteins that are involved in the control of the cell cycle and apoptosis have been investigated, but only a few studies have evaluated the prognostic significance of multiple factors only in rectal carcinomas. The aim of this study was to determine the role of p53, p21, and p27 protein expression as a prognostic factor in rectal carcinomas. Formalin-fixed, paraffin-embedded tissue blocks from 45 rectal adenocarcinomas with appropriate clinical and prognostic data were examined. The standard streptavidin-biotin immunoperoxidase method was used for immunostaining with p53 protein, p21 WAF1/Cip1 protein, and p27 Kip1 protein. The extent of positive p53, p21, and p27 staining was graded semiquantitatively. The clinicopathologic and prognostic features were statistically analyzed. No significant association was found between p53 status and p21 or p27 protein expression (chi2 test, P=0.42 and P=0.18 respectively). There was no correlation between the expressions of p53, p21, and p27, and conventional clinicopathologic features. The mean time interval to recurrence was 25.7+/-24.7 months (range, 0-54 months). p53, p21, and p27 expression was not associated significantly with recurrence and distant metastasis. However, a significant relationship was found between the expression of p27 protein and hepatic metastasis (independent samples t-test, P=0.007). The authors concluded that p53, p27, and p21 protein expression was not related to the clinicopathologic parameters, tumor aggressiveness, metastatic potential, and survival in rectal carcinomas. Further studies are needed to evaluate the predictors of outcome in rectal cancer, considering a variety of prognosticators.

Paclitaxel-carboplatin induced radiation recall colitis.

Some chemotherapeutic agents can "recall" the irradiated volumes by skin or pulmonary reactions in cancer patients who previously received radiation therapy. We report a recall colitis following the administration of paclitaxel-containing regimen in a patient who had been irradiated for a carcinoma of the uterine cervix. A 63-year-old woman underwent a Wertheim operation because of uterine cervix carcinoma. After 8 years of follow-up, a local recurrence was observed and she received curative external radiotherapy (45 Gy) to the pelvis. No significant adverse events were observed during the radiotherapy. Approximately one year later, she was hospitalized because of metastatic disease with multiple pulmonary nodules, and a chemotherapy regimen consisting of paclitaxel and carboplatin was administered. The day after the administration of chemotherapy the patient had diarrhea and rectal bleeding. Histological examination of the biopsy taken from rectal hyperemic lesions showed a radiation colitis. The symptoms reappeared after the administration of each course of chemotherapy and continued until the death of the patient despite the interruption of the chemotherapy. In conclusion, the probability of recall phenomena should be kept in mind in patients who received previously with pelvic radiotherapy and treated later with cytotoxic chemotherapy.