PubMed Health⌕ Search

Biomedical subjects

W F McCarthy

Publications and source records attributed to W F McCarthy.

28 records · Page 2Linked to original sources

Immunohistochemical expression of P53 tumor suppressor gene protein in adult germ cell testis tumors: clinical correlation in stage I disease.

P53 tumor suppressor gene protein immunostaining was evaluated in the primary tumor of adult testicular germ cell cancer to assess if P53 expression would serve as a clinically useful tumor marker. Representative archival tissues from 152 orchiectomy specimens were studied for P53 immunohistochemistry. Seminoma and nonseminomatous germ cell tumor constituents revealed P53 expression via immunohistochemistry in 90% and 94% of the cases, respectively. For seminoma, there was a trend toward decreased P53 expression with advancing stage. For nonseminomatous germ cell tumor, although all cellular components showed variable P53 expression, P53 expression in embryonal carcinoma constituents increased among stages of disease. A third of pathological stage I cancer patients exhibited 2+ or greater P53-embryonal staining compared with 61% with stage II (p = 0.0670) and 67% with stage III (p = 0.0815) disease, respectively (Kruskal-Wallis, 2-sided test). As a secondary objective, we wanted to determine if P53 immunohistochemistry would be useful to predict occult disease in clinical stage I nonseminomatous germ cell tumor. This group was studied for P53-embryonal immunohistochemistry, the presence of vascular invasion and the quantitative determination of percentage of embryonal carcinoma in the primary tumor in a multivariate fashion to assess if these tests could be clinically useful to predict occult disease. Degree of P53 immunostaining of the embryonal component in the primary tumor was statistically greater for stage II by univariate logistic regression analysis (p = 0.0362). Similarly, the per cent embryonal cancer (p = 0.0002) and vascular invasion (p = 0.0005) were highly significant as predictors of occult stage II disease via the univariate testing. By multivariate logistic regression analysis, the model consisting of per cent embryonal cancer and vascular invasion provided the best prediction of occult disease in the clinical stage I cohort. In addition, this model had the highest sensitivity and specificity of all multivariate models considered. The addition of P53-embryonal staining did not improve predictability nor sensitivity/specificity. The P53 tumor suppressor gene protein is expressed to some degree in most testicular germ cell tumors and degree of staining/expression varies according to stage of disease. From the standpoint of a clinically useful primary tumor risk factor for predicting occult disease, vascular invasion by the tumor and percentage of embryonal carcinoma component in the tumor are more useful than P53 immunohistochemistry.

Adult↗

Diagnostic considerations in molar gestations.

Hydatidiform moles (HMs) are classified as partial or complete based on a combination of gross, histologic, and karyotypic features. Adherence to strict and reproducible diagnostic criteria is needed to ensure accurate diagnosis and minimize interpathologist variability. Using the kappa statistic as a measure of agreement, the morphologic, flow cytometric, and clinical features of 80 cases of HM or suspected HM were analyzed sequentially by three pathologists to evaluate intrapathologist and interpathologist variability. Poor interpathologist agreement was obtained when histology alone was used for diagnosis. The combination of gross morphology and histology resulted in poor to good agreement. Good interpathologist agreement was obtained, however, when objective data (DNA content determined by flow cytometry) were included in the analysis. Our data indicate that pathologist concordance is maximized when the diagnosis is based on a combination of morphology and DNA content.

Adolescent↗

Flow cytometric and quantitative histological parameters to predict occult disease in clinical stage I nonseminomatous testicular germ cell tumors.

The goal of this study was to determine if deoxyribonucleic acid (DNA) flow cytometric and quantitative histological parameters could predict occult metastases in clinical stage I nonseminomatous testicular cancer. Archival paraffin primary tumor tissue was available from 36 clinical stage I nonseminomatous germ cell testicular cancer patients who all had retroperitoneal lymphadenectomy and followup defining 2 groups: pathological stage I (23) and occult pathological stage II (13). Archival blocks were microdissected and individual histological components were subjected to flow cytometry. In addition, the primary histology was reevaluated for vascular invasion and per cent composition of histological components of embryonal carcinoma and other histologies. For flow cytometry parameters, no tumor was uniformly diploid, and the DNA index and per cent S phase cells were not useful in differentiating stages. Although mean per cent S phase for the aneuploid cell population and proliferative index were significantly greater for stage II cases by univariate logistic regression analysis, they are approximately 70% accurate in predicting occult disease as single tests and were not significant by multivariate analysis. The calculation of per cent embryonal carcinoma was also significantly greater in stage II cancer by univariate logistic regression testing and remained significant by multivariate analysis. Vascular invasion was marginally predictive of occult disease but was also not significant by multivariate analysis. Calculating the percentage of embryonal carcinoma of a primary testicular tumor may be a useful method to assess clinical stage I cancer patients for risk of occult disease. A larger study is needed to confirm the importance of per cent embryonal carcinoma and to clarify further if flow cytometry in combination is useful.

DNA, Neoplasm↗

Predicting prognosis of gastrointestinal smooth muscle tumors. Role of clinical and histologic evaluation, flow cytometry, and image cytometry.

Both flow cytometry (FCM) and morphometry have been proposed as techniques for predicting the prognosis of gastrointestinal (GI) smooth muscle tumors (SMTs). In particular, DNA aneuploidy by FCM has been associated with high histologic grade and shortened survival, whereas the DNA index determined by image cytometry has been proposed as a criterion for the diagnosis of malignancy. To further define the potential roles of these two techniques, we performed a variety of morphometric and FCM measurements on paraffin blocks from 122 patients with GI SMTs, with a median follow-up period of 6 years, together with assessments of tumor size and mitotic activity. None of the morphometric measurements (nuclear perimeter, area, form factor, longest diameter, average ferret diameter, equivalent diameter, and DNA index) was a significant prognostic factor when analyzed using a univariate Cox model. In contrast, the flow cytometric mean channel number, the fraction of cells in G2M, aneuploidy of the G0/G1 peak, aneuploidy of the G2M peak, tumor size, and mitotic activity index were statistically significant in univariate models, together with the patient age and sex, and whether or not the patient presented with metastases. In a multivariate model, > 10 mitotic figures per 50 high-power fields and metastases indicated a poor prognosis. If metastasis was not allowed to enter the model, the mitotic index and aneuploidy of the G2M peak portended a poor prognosis.

Female↗

Renal oncocytoma and carcinoma: failure of differentiation with CT.

The authors studied the hypothesis that oncocytoma and adenocarcinoma of the kidney can be differentiated with computed tomographic (CT) criteria and that differences would become more apparent as tumors enlarged. On contrast material-enhanced scans, homogeneous attenuation throughout the tumor and a central, sharply marginated, stellate area of low attenuation were considered predictors of oncocytoma. Any area of decreased attenuation in the tumor except for a stellate, central area was used as a predictor of adenocarcinoma. Among oncocytomas larger than 3 cm in diameter, 67% exhibited the criteria for oncocytoma and 33% met the criterion for adenocarcinoma; among smaller oncocytomas, the respective results were 82% and 18%. Among adenocarcinomas larger than 3 cm in diameter, 84% fulfilled the criterion for malignancy and 16% were incorrectly predicted to be oncocytomas; among smaller adenocarcinomas, the respective results were 58% and 42%. The authors conclude that the CT criteria used are poor predictors of the diagnosis of oncocytoma or adenocarcinoma regardless of tumor size.

Adenoma↗

Immunocytochemistry in the differential diagnosis of effusions: use of logistic regression to select a panel of antibodies to distinguish adenocarcinomas from mesothelial proliferations.

Many studies have shown immunohistochemistry to be beneficial in discriminating between adenocarcinoma and mesothelial reactions in effusions. Although many of these studies suggest using a panel of antibodies, none of them used statistical methods to optimize their choice of assays. In the current study, stepwise logistic regression was applied to our data to select an appropriate panel of antibodies to differentiate between adenocarcinoma and all types of mesothelial proliferations. One hundred effusions (64 cases of adenocarcinoma, 27 cases of benign mesothelial proliferations, and 9 cases of malignant mesothelial proliferations) were analyzed for their reactivity with anti-EMA, anti-MFG, anti-CEA, Leu-M1, B72.3, and the newly described epithelial membrane marker BER-EP4. An abbreviated panel consisting of anti-CEA, EMA, and B72.3 was shown to be sufficient in over 95% of our cases to accurately characterize a given effusion. When all three assays are negative, a diagnosis of adenocarcinoma is extremely unlikely, while when two or three of the assays are positive a diagnosis of adenocarcinoma is almost certain. The use of stepwise logistic regression has proven useful in the design of antibody panels as an adjunct to the differential diagnosis of effusions and may be applicable to the selection of panels in other diagnostic problems.

Adenocarcinoma↗

Comparison of cardiac findings in patients with mitral valve prolapse who die suddenly to those who have congestive heart failure from mitral regurgitation and to those with fatal noncardiac conditions.

Sudden death occurs in a small but important subset of patients with mitral valve prolapse (MVP). Clinical criteria for identifying patients at risk for sudden death have been elusive. To determine if certain morphologic characteristics were present in hearts from patients with sudden cardiac death and MVP, autopsy hearts from persons with sudden death and isolated MVP who were previously asymptomatic or had a history of cardiac arrhythmias (n = 27) were compared with (1) hearts from patients with congestive heart failure (CHF) and mitral regurgitation (MR) secondary to MVP (n = 14), and (2) hearts from persons dying from non-cardiac causes in which MVP was an incidental finding (n = 19). Patients who died suddenly were younger than both patients with MR/CHF and incidental cases (37 +/- 10 vs 65 +/- 16 and 58 +/- 21 years, respectively, p less than 0.001). Mitral valve annular circumference, anterior and posterior mitral valve leaflet lengths, posterior mitral valve thickness, and presence and extent of endocardial plaque were greater in hearts from patients with sudden death than hearts from those with incidental MVP. Hearts from patients with MR/CHF weighed significantly more, had greater left and right atrial cavity sizes and left ventricular cavity diameter than hearts from both sudden death and incidental cases.

Age Factors↗

Preliminary results of three-dimensional reconstruction of previously imaged prostates.

In patients with biopsy proven prostate cancer, preoperative transrectal magnetic resonance imaging (MRI) and ultrasound were performed, followed by total prostatectomy. Generally, the findings with MRI correlated well with the histopathologic findings, including infiltration of and extension through the capsule into periprostatic tissue and the seminal vesicles. False negative results with MRI included centrally located tumors and small tumors. False positive results with MRI included lobular atrophy, cystic hyperplasia, cystic atrophy, florid glandular hyperplasia and scars with chronic inflammation.

Humans↗

Cortical gyrification in the rhesus monkey: a test of the mechanical folding hypothesis.

A quantitative measure of the degree of cortical folding was used to test the mechanical hypothesis of cortical folding and to analyze structural properties of the rhesus monkey cortex. The rhesus monkey cortex has both its maximal degree of cortical folding and the largest ratios of supragranular laminae to the lower granular and infragranular layers in the caudal cortex, over the posterior parietal-anterior occipital regions. Low values for cortical folding and for the ratios of inner and outer cortical layers characterize frontal regions. Topographically intermediate regions are intermediate in both sets of values. Ratios of the amounts of white and gray matter have a topographic pattern that differs from those of cortical folding, suggesting that the sizes of subcortical axonal bundles are not directly associated with the degree of cortical folding. Whereas differences in mean degrees of cortical folding are correlated with brain weights among species of primates, the amount of folding is not associated with brain weight within the species.

Animals↗