Biomedical subjects

Susan Groshen

Publications and source records attributed to Susan Groshen.

60 records · Page 4Linked to original sources

PubMed2002

Potential role of platelet FcgammaRIIA in collagen-mediated platelet activation associated with atherothrombosis.

Collagen-mediated platelet activation contributes significantly to coronary and cerebrovascular thrombus formation associated with atherosclerotic plaque destabilization. Recent clinical and laboratory observations support a potential role for the platelet Fc receptor (FcgammaRIIA) in this process. The purpose of this study was to elucidate any association between platelet Fc receptor (FcR) expression levels and both atherosclerosis risk factors (ARFs) along with collagen-dependent platelet activation. Age and gender-independent variation has been described in the expression of this receptor that is stable over time. Platelet Fc surface expression was compared between patients experiencing an acute coronary or cerebrovascular event, healthy patients with two or more ARFs, and healthy patients with fewer than two ARFs. Platelet FcR expression was significantly and stably (6-52 weeks, mean 20 weeks) increased in 101 patients with acute myocardial infarction, unstable angina, or ischemic stroke syndrome (P<0.001) and 38 healthy patients with two or more ARFs (P=0.027) compared with 109 healthy patients with fewer than two ARFs. Patients with diabetes mellitus from all groups had significantly increased platelet FcR expression over those without diabetes (P<0.0001). Platelet aggregation studies suggested a correlation between number of ARFs per patient, platelet Fc expression levels, and relative sensitivity to collagen stimulation. Platelet FcR surface expression is increased in patients with an acute coronary or cerebrovascular event, non-acutely ill patients with two or more ARFs, and in patients with diabetes mellitus. Increased platelet FcR expression may therefore contribute towards risk for atherothrombotic events.

Adult↗

PubMed2002

Comparison of different antibodies for detection of progesterone receptor in breast cancer.

Monoclonal antibodies directed against human estrogen receptor (ER) and progesterone receptor (PR) have been used extensively for biochemical and immunohistochemical detection of receptors independent of hormone-binding assays. These antibodies have been valuable both for experimental work and for detection of receptors in clinical breast cancer specimens. The purpose of this study was to characterize the sensitivity and specificity of different antibodies for detection of PR by immunohistochemistry (IHC) of formalin-fixed paraffin breast carcinoma sections. The panel of twelve antibodies included two new ones (PgR636 and PgR1294) produced prospectively to be resistant to formalin fixation and paraffin embedding. Fifty-nine breast carcinomas, having known PR levels by biochemical ligand-binding assay, were used to prepare multitumor paraffin-embedded tissue blocks for characterization of the PR antibodies. Of all the antibodies tested, both PgR636 and PgR1294 stained the highest percentage of breast carcinomas known to be positive by the biochemical assay (95-98%) and they exhibited the highest concordance with the biochemical assay (88-90%). The PgR636 and PgR1294 antibodies, along with one other, PR 88, also gave the highest intensity of nuclear staining, while PgR636 and PgR1294 stained the highest mean percentage of tumor cell nuclei. Antigen retrieval was not necessary for PR immunostaining by PgR636 and PgR1294 in most tumors and other tissues examined, but did slightly increase the staining intensity. The majority of the other antibodies tested were highly dependent on antigen retrieval; only PR 88 and KD 68 antibodies approached the performance of PgR636 and PgR1294 without antigen retrieval. These results indicate that PgR636 and PgR1294 are optimal antibodies for IHC detection of PR in routine paraffin tissue blocks.

Animals↗

PubMed2002

Thrombospondin-1 expression in patients with pathologic stage T3 prostate cancer undergoing radical prostatectomy: association with p53 alterations, tumor angiogenesis, and tumor progression.

OBJECTIVES: To investigate thrombospondin-1 (TSP) expression in patients with prostate cancer undergoing radical prostatectomy. TSP is a p53-dependent inhibitor of tumor angiogenesis. Previous studies have demonstrated that TSP expression is significantly associated with the microvessel density (MVD) count, p53 expression, and disease-specific and overall survival in patients with invasive bladder cancer undergoing radical cystectomy. METHODS: Radical prostatectomy specimens from 85 patients with pathologic Stage T3 disease were analyzed for TSP expression, p53 nuclear reactivity, and MVD using antigen-retrieval immunohistochemistry. The median follow-up after surgery was 10.6 years (range 1.8 to 15.4). Disease recurrence was defined as a prostate-specific antigen level of 0.2 ng/mL or greater on two consecutive occasions after surgery. TSP expression was graded as present or absent on the basis of the immunoreactivity in the extracellular matrix by persons unaware of the clinical outcome. Specimens were considered p53 positive (altered) if more than 10% of the tumor cells demonstrated nuclear reactivity. The chi-square test was used to determine whether the associations were significant between the pathologic tumor characteristics and the immunohistochemical findings. The log-rank test was used to determine the associations between the immunohistochemical findings and disease recurrence. RESULTS: TSP and p53 were graded as positive in 21 (26%) and 16 (19%) tumors, respectively. The median MVD count was 111.5. No significant associations were found among p53 status, TSP expression, and MVD. Seminal vesicle invasion and Gleason pattern 4 or 5 disease were significant predictors of disease recurrence. A trend was noted toward a higher rate of disease recurrence for patients with altered p53 expression (p53 positive) or increased MVD. TSP expression was not associated with disease recurrence. CONCLUSIONS: We found no significant association between TSP expression and p53 status, MVD count, or outcome after radical prostatectomy for patients with pathologic Stage T3 prostate cancer. Our data suggest that p53 and MVD may be associated with outcome in these patients. Additional studies are needed to identify reliable molecular markers of outcome for patients with this disease.

Adenocarcinoma↗

PubMed2002

The role of retinoid X receptor messenger RNA expression in curatively resected non-small cell lung cancer.

BACKGROUND: Retinoid X receptors (RXRs) have inhibitory effects on non-small cell lung cancer (NSCLC) cell growth, and RXRbeta expression is reduced in NSCLC specimens compared with normal lung tissue. We hypothesized that suppressed RXR expression might be a prognostic factor of worse clinical outcome in patients with NSCLC. EXPERIMENTAL DESIGN: Using a quantitative real-time reverse transcription-PCR (TaqMan) method, we analyzed RXRalpha, RXRbeta, and RXRgamma mRNA expression in normal lung tissue and matching tumor samples from 88 patients with NSCLC. RESULTS: The median mRNA expression levels of all three RXR subtypes were frequently decreased in tumor tissues compared with matching normal lung tissue (RXRalpha, 67%; RXRbeta, 55%; RXRgamma, 89%). The RXRalpha(P = 0.001) and RXRgamma(P < 0.001) median expression levels were significantly lower in the tumors. Patients whose tumors exhibited low RXRbeta expression levels had a statistically significant worse overall survival (P = 0.0005), whereas a trend toward worse survival was observed for patients with low RXRalpha expression. Multivariate analysis indicated that low RXRbeta expression is an independent predictor of worse survival in patients with NSCLC (P = 0.017). CONCLUSION: Suppressed mRNA expression of all three RXR subtypes is a frequent event in NSCLC. Reduced RXRbeta expression might be an important biomarker for more aggressive disease in patients with NSCLC.

Adult↗

PubMedDate not supplied

The International Bladder Cancer Bank: proposal for a new study concept.

At present, results of marker studies are often inconsistent and sometimes contradictory. Recognized problems include multiple different methods of performing the assays, different subsets of patients and different endpoints, leading to incompatible datasets. Although there has been discussion of establishing general methodological principles and guidelines (analogous to those for clinical trials) for design, conduct, analysis, and reporting of marker studies, these have not been widely implemented. There are no well-recognized prototypes or examples that the urologic researcher can use to model future marker studies. We will discuss our plans to establish a multi-institutional bladder cancer data base and virtual tumor bank as a resource for participating institutions to evaluate the biological and prognostic significance of potential markers for bladder cancer. Samples will be identified and stored at each participating institution and will be available for analysis. A standard, minimal set of patient and pathologic information will be collected. The use of common software, as part of this proposal will facilitate the data transfer of updated patient information to a central database. All contributing centers will have access to summarized information, also to simplify the process of finding collaborating partners. Prospectively collected, consistent datasets with available long-term follow-up, should provide information sooner than with a conventional prospective study. Furthermore, the quality of these data and samples may be superior to that of retrospectively collected data and samples. The proposed International Bladder Cancer Bank of specimens and data will be an effective tool during all phases of marker development.

Biomarkers, Tumor↗

PubMedDate not supplied

LEA.135 expression: identifies low-risk patients with breast ductal carcinoma in situ.

The expression of a cell surface-associated sialoglycoprotein (LEA.135), which has been shown to be significantly associated with decreased incidence of recurrence and increased overall survival of patients with primary invasive breast carcinoma, was evaluated in a retrospective study to identify subsets of patients with breast ductal carcinoma in situ (DCIS) who are at high risk of subsequently developing invasive breast carcinoma. The study was carried out by an immuno-histochemical method on formalin-fixed and paraffin-embedded tissue sections from 63 patients initially with DCIS. Pathological parameters such as DCIS histological type, nuclear grade, as well as time and type of recurrence (either a second DCIS or the diagnosis of locally invasive breast carcinoma) together with follow-up in years were available for the cohort of patients. A comparison of recurrence was made of patients whose tumor cells exhibited LEA.135 expression (24 +/- 8% recurring by 7 years), compared with those patients whose specimens showed the absence of LEA.135 expression (41 +/- 10% recurring by 7 years). A statistically significant univariant association between LEA.135 expression and the absence of recurrence of DCIS or development of locally invasive breast carcinoma was observed, suggesting a favorable prognostic significance of LEA. 135 expression (log-rank p = 0.032). It is worthy of mention that none of the LEA. 135-positive patients developed recurrence as DCIS or locally invasive breast carcinoma (0.24 +/- 0.08) after 5 years of the initial diagnosis of DCIS, whereas those from LEA. 135-negative progressively increased their recurrence at 5 years (0.30 +/- 0.09), 7 years (0.41 +/- 0.10) and 10 years (0.63 +/- 0.12). The results of this pilot study show that LEA.135 expression is significantly associated with a favorable prognosis of patients with DCIS, leading to a decreased incidence of recurrence.

Breast Neoplasms↗