Biomedical subjects
Publications and source records attributed to A Sahin.
A rare case of primary renal carcinoid tumour is presented. The diagnosis was based on immunohistochemically diffuse cytoplasmic positivity for chromogranin A and neuron-specific enolase, in addition to histologic findings. Only 14 previous cases of this tumour have been documented in the literature.
To better understand the timing for presentation of allelic losses in human breast carcinogenesis, we compared the allelotypic profile of 23 in situ ductal carcinomas with that of 29 invasive ductal carcinomas. We also compared the allelotype of the invasive ductal breast carcinomas with that of 23 invasive lobular breast carcinomas. These studies were performed by means of microsatellite length polymorphisms from microdissected paraffin sections. We observed that involvement of chromosome arms 1p, 3p, 3q, 6p, 16p, 18p, 18q, 22q, and possibly 6q and 11p appear to be late events in breast cancer progression because allelic losses or imbalances affecting these areas were observed with very low frequency at the in situ stage. On the other hand, allelic imbalances and losses affecting chromosome arms 7p, 16q, 17p, and 17q appear to be early abnormalities because they were observed in approximately 25-30% of ductal carcinoma in situ lesions. Allelic losses and imbalances affecting the 8p arm were frequently observed in invasive lobular breast carcinomas. It was also interesting that microsatellite instability, also known as replication error (RER) phenotype, was found to occur at a high frequency in invasive lobular breast carcinomas because 9 of 23 (39%) were RER+, compared with 7 of 52 (13.5%) RER+ of breast cancers with ductal differentiation (P = 0.012, chi 2 test). Our findings provide for the first time molecular evidence suggesting that invasive lobular breast carcinomas may arise by a different mechanism of carcinogenesis than ductal carcinomas.
The analysis of haemoglobin is routine in medical laboratories for the purpose of assessing blood disorders and related pathologies. Haemoglobin is structurally diverse and possesses many variant forms, some disease-producing. With recent improvements in technology, capillary electrophoresis is now being adapted in the clinical laboratory. This paper describes the analysis of haemoglobin variants using uncoated fused-silica capillaries. The effects of using different buffer salts at different concentrations with different buffer pH values to separate haemoglobin variants in these capillaries are described.
Forty-nine women with ductal carcinoma in situ (DCIS) treated with lumpectomy and irradiation were studied retrospectively. The median age was 50 years (range, 29 to 73 years) and the median follow-up time from initiation of therapy was 86 months (range, 17 to 230 months). Twelve patients presented with palpable masses (0.4 to 4 cm), three with breast thickening, and three with nipple discharge. In 31 patients the tumors were detected by mammography. Intraoperatively, excision of lesions was confirmed by specimen x-ray (38 specimens) or gross inspection (five specimens) and was recorded to be complete. No record was available in the other six patients. Margins of excision free of DCIS were microscopically confirmed in 25 specimens. The size of impalpable DCIS lesions recorded in 25 patients ranged from 0.4 to 5.0 cm (mean, 1.5 cm). Using Lagios' classification system, there were 18 classic comedocarcinomas, high nuclear grade (NG) with necrosis; seven cribriform/papillary, high NG with necrosis; 17 cribriform/micropapillary, intermediate NG with or without necrosis; and seven cribriform/micropapillary, low NG without necrosis. In two patients residual malignant calcifications were present on the postoperative mammogram. Disease recurred in the treated breast at the site of incision in five patients at 18 months and 8, 11, and 12 (two patients) years from initial therapy. The rate of local disease recurrence was 2% at 5 years and 6% at 10 years; three recurrences showed invasive ductal carcinoma and two were DCIS. To evaluate risk factors the following characteristics were considered: necrosis, NG, histological type, periductal fibrosis, periductal lymphoid infiltrate, margin status, age, and method of tumor detection. The end points chosen were recurrence and death from any cause (because only one patient died of disease). Although the recurrences were attributed to residual disease in two patients, of the clinical and pathological parameters evaluated, only periductal fibrosis showed a significant relationship with outcome, with a P value < or = .05 by the Wilcoxon test. On the other hand, using the proportional hazards model, necrosis was a significant predictor for recurrence (P = .02), as was the pair fibrosis and tumor detection when taken together (P = .05). Fibrosis significantly associated with high NG, Lagios' histological subtypes I and II, periductal lymphoid infiltrate, and necrosis (P < or = .0006).(ABSTRACT TRUNCATED AT 400 WORDS)
OBJECTIVES: We examined the serum ferritin levels in 158 patients with renal cell carcinoma and 101 healthy control subjects between 1987 and 1994 to investigate the value of this intracellular protein as a tumor marker. METHODS: Preoperative and postoperative serum ferritin values were analyzed and the patients were stratified to three groups accordingly: group 1, patients with normal values (N-N); group 2, those with preoperative high and postoperative normal (H-N); and group 3, those with preoperative normal or high with postoperative high ferritin levels (H-H). RESULTS: The mean serum ferritin level in 101 healthy control subjects was 85.7 +/- 63.6 ng/mL (range, 3.7 to 265.2). The upper limit of normal, which was calculated by adding 2 standard deviations to the mean was 219.9 ng/mL. Mean serum ferritin in patients with renal cell carcinoma was 274.2 +/- 276.3 ng/mL, which was significantly higher than that of control values (P < 0.01). The sensitivity, specificity, and overall accuracy rate for ferritin increase was 94%, 50%, and 61%, respectively. Multivariate analysis showed that the aforementioned grouping and stage of the disease were the two independent prognostic parameters. Preoperative ferritin levels lost its significance on multivariate analysis. CONCLUSIONS: Our study shows that although serum ferritin was a useful tool in diagnosing and staging patients, it was not ideal in early stages. However serum ferritin seems to be more valuable for follow-up; postoperative values, indeed, predict the prognosis.
With the advanced imaging techniques, the sensitive assays for tumor markers and the curability of small-volume metastatic disease with cis-platinum-based chemotherapy, surveillance has gained popularity in clinical stage-I non-seminomatous germ-cell tumors. This study reports our experience on 58 patients who have been included in a surveillance protocol. Patients with normal tumor-marker levels following surgery, no evidence of metastases on the CT scans of the abdomen and the chest and no residual tumor at the surgical margin were followed. Relapsing patients were treated with cis-platinum-based combination chemotherapy. Of the 58 patients, 17 relapsed (29.3%) in a period of 2-18 months (median 5 months). None of the relapsing patients later presented with evidence of disease in the follow-up period 14-79 months (median 39 months) after chemotherapy. Prognostic factors were evaluated by univariate analysis and the data for risk factors, such as the presence of embryonal carcinoma, absence of yolk-sac elements and scrotal violation, were evaluated by multivariate analysis. Statistical analysis showed that none of the risk factors were significantly different in predicting the relapse. Of the 6 relapsing patients with preorchiectomy elevated tumor-marker levels, 4 had shown a slower decline in tumor-marker levels than expected and they all relapsed with elevated levels of the same tumor markers. A surveillance-only policy actually seems to be a safe and logical approach if the patients are properly selected and cooperate fully.
Microcystin and related toxic peptides produced by cyanobacteria (blue-green algae) are potent and selective inhibitors of protein phosphatases 1 and 2A. We adapted existing enzymatic techniques to analyze the liver of rainbow trout after oral administration of hepatotoxic cyanobacteria. Liver tissue was removed 3 and 12 hours after treatment, and phosphatase activity was determined in liver extracts, using a specific phosphoprotein substrate. In all samples from fish exposed to toxic cyanobacteria, phosphatase activity was suppressed, whereas the control enzyme, lactate dehydrogenase, present in the same liver extract, was not affected by cyanobacteria. Thus, experimental poisoning by hepatotoxic cyanobacteria resulted in an abnormally low ratio of phosphatase to lactate dehydrogenase activity in the liver extracts. These results indicate that specific inhibition of phosphatases 1 and 2A may provide a useful diagnostic tool to determine the early effects of cyanobacteria toxic peptides directly in liver samples from poisoned animals. Although this test was developed with rainbow trout, it should be possible to extend the analysis of liver phosphatase activity to other species, including sheep and cattle, which are frequently affected by hepatotoxic cyanobacteria.
Sialyl-Tn (STn) antigen represents an aberrant glycosylation product of cell surface mucin in adenocarcinomas. We studied its expression in 40 breast carcinomas (35 of which included in situ carcinomas) by performing immunostaining with B72.3 monoclonal antibody. STn expression was observed in 50% of cases and was equally frequent in in situ and in invasive carcinomas. Positive STn staining significantly correlated with high nuclear grade (P = 0.001), aneuploidy (P < 0.001) and high S-phase fraction (P = 0.02). No correlation was observed between STn staining and age, menopausal status, presence of invasive component, or hormone receptor positivity. STn staining may provide an objective marker of dedifferentiation of breast tumors and should be investigated further for its prognostic value in breast cancers and as a biomarker of malignant transformation of breast epithelium.
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Mesoblastic nephroma is the most common renal tumor in infancy but is infrequent in the adult. It has a typical histological pattern but its histogenesis is unknown. We report a case of mesoblastic nephroma in an eighteen year old man who was treated by conservative surgery.
We report a case of renal cell carcinoma presenting with bilateral adrenal masses diagnosed by ultrasonography four years after nephrectomy. The histopathological examination of the trucut biopsy specimens obtained percutaneously by ultrasound guidance revealed bilateral adrenal mestastases of renal cell carcinoma.
Current chemoprevention trial designs based on epidemiological risk assessment and occurrence of cancer as an endpoint are inefficient and expensive. Novel biomarkers are needed to facilitate the development of chemopreventive interventions. The following four categories of biomarkers may be useful in prevention trials: histologic and morphometric markers; phenotypic markers of dysregulated proliferation, differentiation, and cell loss; specific oncogenes and growth regulators which are qualitatively or quantitatively altered in breast cancers; and markers of genetic and epigenetic instability. Some of these markers will be generally useful regardless of the chemopreventive approach used, whereas others may be uniquely useful in trials of specific chemopreventive agents [e.g., upregulation of progesterone receptor (PR) expression in response to tamoxifen]. The development of these markers requires three phases of study: "Phase I": assessing the prevalence of the putative marker in malignant and premalignant tissue from individuals who have developed breast cancer; "Phase II": assessing in vivo modulation of the biomarker by the proposed chemopreventive agent; and "Phase III": applying the proposed biomarker in larger-scale trials of chemopreventive agent in high-risk populations, either before or after the development of a primary breast malignancy. The use of these biomarkers may also allow identification of novel targets for chemoprevention.
Ultrasonographic findings in nine cases of peritoneal mesothelioma are presented. The most common findings were sheet-like or nodular peritoneal thickening, soft tissue masses, fixation of the intestinal loops, mesenteric thickening, and minimal ascites which was disproportional to the degree of tumor dissemination. The authors found that abdominal sonography, using 3.75-7.5 MHz transducers, is a useful imaging method for diagnosis of peritoneal mesothelioma in high-risk groups.
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We reevaluated 46 patients with histopathologically proven stage A and B renal cell carcinoma, who underwent radical nephrectomy for the presence of ipsilateral adrenal gland in the surgical specimens. It turned out that 23 specimens included ipsilateral adrenals. Two patients without adrenalectomy relapsed locally, whereas no local recurrence was noted in patients whose adrenals were removed. Three years' disease-free survival rates (DFS) for patients with and without adrenalectomy were 100% and 78%, respectively. Although no statistical difference was found in terms of DFS between patients with and without adrenalectomy, we suggest the removal of the ipsilateral adrenal gland if technically feasible.
Thirteen patients with advanced urothelial transitional cell carcinoma were treated with methotrexate, vinblastine, adriamycin and cisplatin combination. No complete remissions were achieved in patients with disseminated diseases; only three out of five patients (60%) with localized tumours in the bladder or perivesical space responded completely. Localized tumour recurrences in the bladder occurred in two of three complete responders at the ninth and tenth months after chemotherapy. Four patients died during or after chemotherapy: one from disease progression and the remainder from chemotherapy complications. Authors conclude that, although 23% complete and 30.8% partial remissions were achieved with the MVAC chemotherapy, strict toxicity monitoring and careful selection of patients are essential because of its non-negligible complications.
Two cases of Leydig cell tumour of the testis with no hormonal and metastatic manifestations are presented. Clinical features of the disease are discussed.
BACKGROUND: The clinical behavior of the tumor in patients with locally advanced bladder carcinoma is unpredictable. Current predictors of clinical behavior include depth of muscle invasion, presence of vascular invasion, proliferation rate, and loss of blood group antigens. Treatment selection would be facilitated by the development of a reliable marker of tumor progression. Functional retinoblastoma (RB) gene loss has been reported to occur in bladder carcinoma, but the significance of this loss is unknown. PURPOSE: We have evaluated the frequency of functional loss of the RB gene in locally advanced bladder carcinoma and have compared the results to known prognostic factors in the same cohort. METHODS: Forty-three study patients with pathologically well-characterized, locally advanced bladder carcinoma, who were placed in a protocol incorporating surgery and chemotherapy, were studied for known clinical and pathological prognostic indicators as well as for their Rb status. Formalin-fixed and paraffin-embedded archival primary tumor tissues were used for histological and immunohistochemical analyses. RESULTS: Altered Rb protein expression was documented in 37% of the tumor specimens. The high rate of altered Rb expression found in this cohort with advanced urothelial tumors strongly suggests that RB functional loss may be associated with tumor progression in this malignancy. Altered Rb protein expression was found to be independent of other known prognostic variables. A significantly poorer tumor-free survival rate also was noted for those patients who had a tumor with an altered Rb protein with or without vascular invasion. CONCLUSION: The high frequency of Rb alteration in locally advanced bladder carcinomas, plus the fact that a significant correlation could not be found between the Rb status and other known prognostic markers in this preliminary study, suggests that altered RB expression may be an independent prognostic marker of tumor progression in bladder cancer.