Banu Sis

Desmoplasia measured by computer assisted image analysis: an independent prognostic marker in colorectal carcinoma.

Aims: The assessment of desmoplasia by traditional semiquantitative methods does not provide reliable prognostic data. The aim of this study was to quantify desmoplasia by computerised image analysis in primary colorectal carcinomas and to investigate its ability to predict overall survival. Methods: In total, 112 colorectal adenocarcinomas, with a median follow up of 66 months, were studied. The representative tumour sections were stained by the van Gieson method, which stains collagen rich stroma red. For quantitative histochemical measurement, digital images were analysed by a computerised image analysis program to calculate the percentage of red stained tissue area. The percentage of desmoplasia (PD) was related to conventional clinicopathological prognostic factors and overall survival. Results: The mean (SD) PD was 4.85 (3.37). PD was found to be significantly associated with lymph vessel and venous invasion. By Kaplan–Meier analysis, PD was associated with survival—patients with PD > 4 had a shorter survival than those with PD ⩽ 4. In multivariate analysis, tumour stage, distant metastasis, and PD emerged as independent prognostic factors. Conclusion: Desmoplasia measured by image analysis seems to be a significant prognostic indicator in patients with colorectal carcinoma and the improved method described in this study would be useful for routine prognostication.

BRCA1, C-erbB-2, and H-ras gene expressions in young women with breast cancer. An immunohistochemical study.

Young age does not seem to be directly related to the aggressiveness of the disease among patients with breast cancer. Identification and analysis of the alterations in a susceptibility gene expression in breast cancer occurring in young women may allow identification of those patients in whom tumors will show an aggressive clinical course. The purpose of the present study was to evaluate the association of BRCA1, H-ras, and c-erbB-2 gene expression with clinicopathologic parameters of prognosis in breast cancer. Formalin-fixed, paraffin-embedded tissue from 35 patients with breast cancer younger than 35 years were immunohistochemically stained for BRCA1, H-ras, and c-erbB-2 expression with monoclonal antibodies. For each antibody, immunoreactivity was assessed by a semiquantitative scoring system. Each case was also graded according to the modified Bloom-Richardson criteria and evaluated for Ki-67 labeling index, hormonal status, tumor size, distant metastasis, and axillary lymph node involvement. Strong expression of c-erbB-2 and H-ras were observed in 9 cases (25.7%) and 13 cases (37.2%), respectively. Loss of BRCA1 expression was found in five cases (14.3%). Statistical analysis showed that loss of BRCA1 expression was significantly associated with higher Ki-67 labeling index and greater tumor size. In addition, stronger H-ras expression was significantly associated with lymph node involvement and distant metastasis. However, c-erbB-2 immunoreactivity did not show statistical significance with any prognostic parameters. We conclude that, although care must be taken not to overstate the importance of our results in view of the lack of information on clinical outcome, alterations in BRCA1 and H-ras gene expression might be of prognostic importance because of the role of H-ras protein on metastatic behavior and the role of BRCA1 protein on tumor growth. However, c-erbB-2 expression seems to be of no importance in the prognosis of breast cancer occurring in young women.

Does angiogenesis predict recurrence in superficial transitional cell carcinoma of the bladder

OBJECTIVES To investigate the role of angiogenesis in predicting tumor recurrence and its correlation with established clinicopathologic prognostic factors in superficial transitional cell carcinoma of the bladder. METHODS The paraffin sections of 80 superficial papillary transitional cell bladder carcinoma specimens were stained with CD31 antibody to label the vascular endothelium using the standard streptavidin-biotin-immunoperoxidase method. The vascular surface density (VSD) equivalent to the vascular surface area per unit of tissue volume and number of vessels per square millimeter of stroma (NVES) were assessed by means of stereology, and these morphometric parameters of angiogenesis were statistically analyzed to interpret the relation to tumor recurrence in addition to tumor stage, grade, size, and number and the presence of carcinoma in situ. RESULTS VSD and NVES values showed no statistically significant difference between pTa and pT1 tumors or patients with and without recurrence. In contrast, VSD and NVES values were found to increase in higher grade tumors (P = 0.019). VSD values were also higher in patients with coexisting carcinoma in situ in pTa tumors (P <0.001). Tumor number and size and recurrence number and time to the first recurrence did not correlate with any vascular parameters. CONCLUSIONS Stereologic assessment of angiogenesis does not help to predict recurrence in superficial bladder cancer. Angiogenic parameters appeared to be well correlated with the conventional histologic grading system. Otherwise, the present study did not show any correlation of angiogenesis with any potential prognostic factors. This may be due to the diverse angiogenic pathways occurring in invasive and superficial tumors.

Matrix metalloproteinase-2 expression in laryngeal preneoplastic and neoplastic lesions.

Matrix metalloproteinase-2 (MMP-2), a member of gelatinases, is particularly important in the digestion of nonfibrillary and denaturated collagens; thus, it may play a role in tissue remodeling and in the invasion of malignant cells. The expression of MMP-2 has not yet been described in preneoplastic lesions of the larynx thus far. The purpose of this study was to evaluate whether the expression of MMP-2 plays a role in early laryngeal carcinogenesis. Laryngectomy specimens of 20 invasive carcinoma cases were studied. The slides with atypical hyperplasia, carcinoma in situ, and invasive carcinoma were selected from laryngectomy specimens. On these slides, 23 atypical hyperplasia and 17 carcinoma in situ areas were identified. MMP-2 expression was scored immunohistochemically on paraffin tissue sections using the avidin-biotin-peroxidase method. MMP-2 expression in all three groups was statistically different. A sequential increase in MMP-2 expression correlated significantly with the hypothesis of multistep carcinogenesis. In contrast, MMP-2 expression was not related to tumor stage, lymph node metastasis, or differentiation in squamous cell carcinomas. In conclusion, this sequential increase in MMP-2 expression points to an altered expression of MMP-2 in early neoplastic transformation in laryngeal mucosa, followed by an increasing expression during the progression of the disease.

Renal medullary changes in renal allograft recipients with raised serum creatinine

Objective: To test the hypothesis that the renal medulla may reflect rejection related changes and thus have a predictive value in the assessment of acute renal allograft rejection or chronic graft damage. Methods: 75 post-transplant biopsies from 57 patients were scored according to the Banff 1997 scheme. The biopsies with adequate cortical and medullary tissue (n = 23) were selected and medullary tissues were reviewed for rejection related lesions except intimal arteritis. Chronic damage was determined by image analysis depending on periodic acid-methenamine silver (PAMS)-Masson trichrome (MT) staining. Medullary and cortical changes were compared. Results: Interstitial inflammation and tubulitis were more frequent and severe in the cortex (p<0.001). Medullary tubulitis was associated with intimal arteritis (p = 0.003, r = 0.598). Medullary interstitial inflammation (n = 8) and tubulitis (n = 4) were associated with cortical borderline changes (n = 5) or allograft rejection (n = 3). The sensitivity, specificity, and positive and negative predictive values of medullary inflammatory changes in predicting cortical allograft rejection were 43%, 69%, 37%, and 73%, respectively. A significant association was observed between medullary MT-SAP and cortical PAMS-SAP values (p = 0.02, R2 = 0.23). Conclusions: Acute rejection related lesions are more common and severe in the cortex, and the renal medulla does not sufficiently reflect cortical rejection. The positive and negative predictive values of medullary changes for allograft rejection are low, and medullary inflammation is not a reliable indicator of allograft rejection. Increased medullary fibrosis is correlated with chronic cortical damage.

Cystic schwannoma of the maxillary sinus

OBJECTIVE Although 25-45% of all schwannomas are reported to occur in the head and neck region, nasal cavity and paranasal sinus involvement is rare, with 32 such cases described till 1999. Of these cases, only three were cystic. Herein we present a cystic schwannoma of the maxillary sinus of a 66-year-old, otherwise healthy male patient. METHODS The tumor tissue was routinely processed, embedded in paraffin, and stained with H&E. Immunostaining was performed for S-100 protein, epithelial membrane antigen (EMA) and cytokeratin. RESULTS A mass with sudden enlargement, inhomogeneous enhancement with cystic areas, S-100 positive membrane-like structures lining the cystic cavity of an otherwise classical schwannoma were the main features encountered in our case. CONCLUSION We recommend that cystic schwannoma should be kept in mind in the differential diagnosis of cystic masses of the maxilla.

Toxicity Induced by he Chemical Carcinogen 7,12-Dimethylbenz[a]anthracene and the Protective Effects of Selenium in Wistar Rats

7,12-Dimethylbenz[a]anthracene (DMBA), a polycyclic aromatic hydrocarbon (PAH), has been used extensively as a tool to initiate mammary carcinogenesis and subsequent chemoprevention. On the other hand, selenium (Se) is potentially useful in oncology because this element possesses anticarcinogenic and chemopreventive properties. Se-containing enzymes such as glutathione peroxidase (GPx) play an important role in PAH metabolism and detoxification. In this study, rats were administered a single, oral dose of DMBA (12 mg). In the Se group, rats received 20 µg Se daily via gavage, starting 2 wk before the DMBA administration and continued for 1 wk. One hundred twenty days after DMBA administration the rats were sacrificed and toxicity was evaluated using histopathological and biochemical criteria. Five rats (30%) died in the DMBA group within the study period, whereas no death occurred in the DMBA–Se-treated group. Malignant tumor frequency was 33% in the DMBA group, while no malignant tumors occurred in the DMBA–Se-treated group. Some inflammatory changes rather than epithelial changes were found upon histopathological examination. GPx activity and blood urea nitrogen levels were higher and kidney GST activity was lower in the DMBA–Se-treated group compared to DMBA alone. In conclusion, Se appears to be effective in preventing some of the adverse effects associated with DMBA. This research has been partially carried out at Dokuz Eylul University School of Medicine, Learning Resources Center Research Laboratory (ARLAB). The authors thank Dr. Ali Riza Sisman for his kind contributions and Prof. Dr. Gul Guner and Dr. Sam Kacew for their helpful advice.

Tc-99m-HMPAO uptake by bronchoalveolar cells.

Lung uptake of intravenously injected Tc-99m-HMPAO is observed in smokers and in lung toxicity due to various agents. We investigated the Tc-99m-HMPAO uptake of bronchoalveolar lavage (BAL) cells in the lungs after incubation inin vitro conditions (6 patients), intravenous injection (IV) (7 patients) and inhalation (INH) (6 patients) of Tc-99m-HMPAO in order to show whether BAL cells are also responsible for Tc-99m-HMPAO uptake in the lungs. Cell/supernatant (C/S) count ratio was 7.0±3.5, 29.3±40.8 and 8.4±4.5 forin vitro, IV and INH groups, respectively. C/Sin vitro showed a positive correlation with % alveolar macrophages (r=0.943, p=0.0048) and a negative correlation with % neutrophils (r=−0.945, p=0.0045). Cells/whole BAL fluid ratio correlated with the amount of daily cigarette consumption in INH group (r=0.95, p=0.0037). Tc-99m-HMPAO showed adherence to mucus after inhalation. Tc-99m-HMPAO diffuses into alveolar spaces after, injection and is present in BAL fluid and BAL cells both after injection and inhalation. Glutathione concentration and oxido-reductive state of the epithelial lining fluid and BAL cells may influence the lung uptake of Tc-99m-HMPAO.

A comparison of the prophylactic uses of topical mupirocin and nitrofurazone in murine crush contaminated wounds.

OBJECTIVES This work was conducted to study the prophylactic efficacy of 2 topical antibiotic ointments (mupirocin and nitrofurazone) against wound infection in experimental contaminated crush wounds. METHODS Male Wistar rats underwent two 2-cm incisions at the back side and randomized into 3 groups--placebo (n = 14), mupirocin (n = 14), and nitrofurazone (n = 14)--and infected with either Staphylococcus aureus or S. pyogenes. All wound edges were crushed for 5 seconds with hemostats to simulate crush injury before inoculation of the microorganisms. Half of the wounds were sutured and the other half left open. These wounds were treated 3 times daily for 6 days with topical mupirocin, nitrofurazone, or petrolatum (as placebo). At the end of 6 days, excisional biopsies were taken from wound edges and histopathologic assessments were made based on neutrophilic infiltration, edema formation, myofibroblastic proliferation, and granulation tissue formation. For the microbiologic assessments, quantitative tissue cultures were made. RESULTS In S. aureus-inoculated wounds, mupirocin showed higher antibacterial activity against bacterial colonization and reduced infection rates compared to placebo groups. The same effect was observed for the infection rates in S. pyogenes-inoculated wounds. In S. pyogenes-inoculated open wounds, nitrofurazone showed higher antibacterial activity against infection, but this effect was not observed in closed wounds. In S. pyogenes- and S. aureus-infected wounds, mupirocin treatment significantly lowered infection rates compared to nitrofurazone treatment. Histopathologic examination showed higher myofibroblastic proliferation and higher volume of granulation tissue in the nitrofurazone groups compared to the mupirocin groups. CONCLUSION Topical mupirocin application was effective against crush wound infections inoculated with S. pyogenes and S. aureus. Nitrofurazone provides better granulation tissue formation, but did not effectively prevent bacterial colonization and infection in crush contaminated wounds.

AN UNUSUAL MESENTERIC PARAGANGLIOMA PRODUCING HUMAN CHORIONIC GONADOTROPIN

Adrenal and extra-adrenal paragangliomas are uncommon neoplasms arising from the parenchymal cells of paraganglia. The presenting symptoms are mostly due to excess catecholamine secretion. Extra-adrenal paragangliomas are mostly localized in the superior para-aortic region of the abdomen. Mesenteric paragangliomas are very rare. We report an unusual case of mesenteric paraganglioma producing human chorionic gonadotropin (hCG). To the best of our knowledge, this is the first case report describing hCG secretion in an extra-adrenal paraganglioma.