Tissue polypeptide antigen in the follow-up of patients with urinary bladder cancer compared with conventional urine cytology.

The incidence of bladder cancer has demonstrated a rapid increase during the last decades. The aim of this study is to determine the clinical value of serum tissue polypeptide antigen (TPA) as a tumour marker for urinary bladder cancer in comparison with conventional urine cytology. Urine and blood samples were obtained from a total of 108 patients (group A) with a known history of bladder cancer, who presented for their routine 3 month follow-up. These 108 patients included 45 patients with high grade and 63 patients with low grade bladder cancer, and 30 patients with lower urinary tract symptoms (LUTS) and no history of bladder cancer (group B). Urine and blood samples from fifty healthy adults (group C) were also tested; this group served as the control group for estimating the normal range of serum TPA values. In all group A patients cystoscopy and/or bladder biopsies were performed. All blood and urine samples were tested for TPA and conventional urine cytology respectively. Results showed that the upper normal range for TPA was 1.0 ng/mL(0.9 ± 0.04) in the control group. For the subgroups of patients with high and low grade bladder cancer elevated serum TPA levels were found in 52% and 40% of the patients respectively. The overall serum TPA sensitivity and specificity were 50% and 85% respectively for patients with known bladder cancer (group A). We found the sensitivity of cytology for high grade bladder (GIII) carcinomas to be 72%; however when urine cytology was combined with serum TPA the overall sensitivity reached 80%. We conclude that serum TPA combined with urine cytology may be used as a prognostic marker for bladder cancer.

Contribution of nuclear morphometry by confocal laser scanning microscopy to the diagnosis of malignant bile duct strictures.

OBJECTIVE: To determine the clinical utility of nuclear morphometry by confocal laser scanning microscopy for the diagnosis of malignant biliary strictures. STUDY DESIGN: The study included 51 patients with bile duct strictures who underwent endoscopic retrograde cholangiopancreatography (ERCP). Based on the initial workup, 6 patients were diagnosed with benign strictures, and 12 patients had malignant strictures, while in the remaining 33 cases the diagnoses were inconsistent, due mainly to inadequate samples. Smears from ERCP brushings were stained for DNA with propidium iodide. Nuclear morphometry was assessed on images acquired by a confocal laser scanning microscope. Three parameters-nuclear volume, nuclear shape and nuclear staining intensity-were calculated. Based on these features, a distinctive nuclear morphometric pattern was attributed to the malignant nuclei, and its predictive value was assessed prospectively in the 33 undiagnosed cases. RESULTS: After an overall median follow-up period of 8 months, 19 patients were diagnosed with malignant strictures, and 14 patients were considered to have benign strictures. With respect to the prediction of malignancy, the sensitivity of the described method was 78%, the specificity was 63%, the positive predictive value was 64%, and the negative predictive value was 80%. CONCLUSION: Nuclear morphometry may provide significant information for the diagnosis of malignant bile duct strictures when conventional cytology fails to.

The expression of metallothioneins on imprint smears of prostate carcinoma: correlation with clinicopathologic parameters and tumor proliferative capacity.

AIMS AND BACKGROUND: Metallothioneins are a family of metalbinding cysteine-rich proteins that play an important role in cellular processes such as proliferation and apoptosis, protection against oxidative stress and metal ion homeostasis and detoxification. Recent findings suggest that metallothioneins might play a significant role in the development and progression of prostate cancer. It has been also demonstrated that Ki67 expression may have prognostic value for disease-free survival in cases of prostate carcinoma. STUDY DESIGN: Imprint smears samples obtained from 70 patients immediately after radical prostatectomy for prostatic carcinoma were immunostained with monoclonal antibodies against metallothioneins and Ki-67. Metallothionein expression was correlated with Ki-67 immunostaining, Gleason score, stage, preoperative prostate-specific antigen levels and biochemical recurrence. RESULTS: Metallothionein expression was shown to correlate strongly with Gleason score (P < 0.001) and significantly with pathological staging and Ki-67 immunostaining (P < 0.001, P < 0.05, respectively). In contrast, no significant association between metallothioneins and preoperative PSA was demonstrated. Both of the studied markers (metallothioneins and Ki-67) correlated with recurrence (P = 0.009, P = 0.006, respectively). CONCLUSIONS: The present findings support the independent predictive value of metallothioneins and Ki-67 in prostate cancer. However, additional data are needed in order to reveal the factors that influence the expression of metallothioneins in epithelial neoplastic cells and clarify their mechanism of action.

Expression of p53 in imprint smears of endometrial carcinoma.

The aims of this study were to determine the expression of p53 protein in endometrial adenocarcinomas (as a potential prognostic indicator before treatment) as well as normal endometrium in imprint smears and to correlate the results with clinicopathologic parameters of primary untreated endometrial cancer patients. Two hundred fifty five patients were evaluated with endometrial imprint cytology during a 29-month period. Endometrial samples freshly resected from women who underwent total abdominal hysterectomy were studied. One hundred twenty six patients had endometrial carcinoma and 129 cases were diagnosed as normal endometrium. The expression of p53 was assessed by immunocytochemistry. Positive staining was correlated with increased surgical-pathological stage, histological grade and lymph node metastases. High expression of p53 staining was significantly more frequent in histological type II than type I endometrial adenocarcinoma. High-grade endometrial carcinoma had higher proportions and stronger intensity compared with low-grade carcinoma. Negative immunostain for p53 protein was found in proliferative, secretory, and atrophic endometrium. Immunocytochemical findings from p53 stain, in addition to cytomorphologic features, appeared to be useful in the diagnosis and in the postoperative prognosis of endometrial carcinoma in endometrial cytology, especially if combined with other markers. High p53 expression correlates with morphologic features of aggressiveness and the expression pattern of p53 correspond to the expected cyclic/atrophic pattern in normal endometrium.

Utility of Ki-67, p53, Bcl-2, and Cox-2 biomarkers for low-grade endometrial cancer and disordered proliferative/benign hyperplastic endometrium by imprint cytology.

In this report, the authors examined the characteristic features of morphology and molecular biology of Ki-67, p53, Bcl-2, and cyclooxygenase-2 (Cox-2) immunocytochemistry in low-grade endometrioid endometrial carcinoma (LG-ENEC) and disordered proliferative (DP)/benign hyperplastic (BH) endometrium. We carried out a prospective study by collecting endometrial imprints from freshly resected uteri over a 20-month period and finally 104 patients were evaluated with endometrial cytology. We focused on LG-ENECs, as well as on BH endometrium and its precursor lesion, DP endometrium, firstly because of the overlapping cytomorphology of these pathologic entities and secondly because of the lack of agreement in the differential diagnosis of atypical hyperplasia from complex hyperplasia and well-differentiated endometrial carcinoma, even in curettage specimens. Ki-67 expression of LG-ENEC showed predominance in comparison with DP/BH endometrium. Furthermore, high levels of Bcl-2 (>50%) were expressed only in DP/BH endometrium. DP/BH endometrium was negative for p53 marker, except from two cases of BH endometrium. Cox-2 expression ≥50% was found only in LG-ENECs. Using Ki-67, Bcl-2, p53, and Cox-2 markers, we managed to distinguish fully DP/BH endometrium from LG-ENEC. Higher Ki-67%/Bcl-2% rate and also higher Cox-2 expression were found in LG-ENEC cases with FIGO stage ≥ IC, than in cases with FIGO stage < IC. The immunocytochemical findings from a combination of Ki-67, p53, Bcl-2, and Cox-2, may differentiate LG-ENEC from DP/BH endometrium with overlapping cytomorphology. Immunocytochemistry appeared to be useful also for the correlation between LG-ENEC and FIGO stage.

Expression of Ki-67 as proliferation biomarker in imprint smears of endometrial carcinoma.

The aims of this study were to determine the expression of Ki-67 in type I and type II endometrial adenocarcinomas as well as normal endometrium in imprint smears and to correlate the results with clinicopathologic parameters of primary untreated endometrial cancer patients. During a 29-month period, 255 patients were evaluated with entometrial imprint cytology. Endometrial samples freshly resected from women who underwent total abdominal hysterectomy were studied. One hundred twenty-six patients had endometrial carcinoma and 129 cases were diagnosed as normal endometrium. The expression of Ki-67 was assessed by immunocytochemistry. Positive staining was correlated with increased stage, grade and lymph node metastases. High expression was more frequent in type II than type I endometrial adenocarcinoma and high-grade endometrial carcinoma had higher proportions of Ki-67 positive immunostaining compared with low-grade carcinoma. Proliferative endometrium showed high Ki-67 expression level, even higher than those of grade 1 and type I. On the other hand, secretory endometrium Ki-67 positive cells were markedly diminished and even disappeared. Completely negative staining was found to be related to atrophic endometrium. Immunocytochemical findings from Ki-67 stain, in addition to cytomorphologic features, appeared to be useful for the diagnosis of endometrial carcinoma in endometrial cytology with imprint smears. High Ki-67 expression correlates with morphologic features of aggressiveness and the expression pattern of Ki-67 correspond to the expected cyclic/atrophic pattern in normal endometrium.