Biomedical subjects

Susan J Maygarden

Publications and source records attributed to Susan J Maygarden.

8 recordsLinked to original sources

PubMed2006

Pathologic findings from the Breast Cancer Surveillance Consortium: population-based outcomes in women undergoing biopsy after screening mammography.

BACKGROUND: To the authors' knowledge, a comprehensive analysis of pathology outcomes after screening mammography, as it is practiced clinically in the U.S. general population, has not been performed. METHODS: Breast Cancer Surveillance Consortium data from 1996-2001 were used to identify pathology specimens that were obtained within 1 year of screening mammograms performed on 786,846 women ages 40-89 years. The pathology results were classified as invasive carcinoma, ductal carcinoma in situ (DCIS), or benign. The associations between overall pathology outcomes and invasive tumor size and lymph node status were analyzed by age and mammography assessment category. RESULTS: The rates of both recommending and performing a biopsy varied little with age. The 1,664,032 screening mammograms were followed by 26,748 known biopsies (1.6%) and 8815 diagnoses of breast carcinoma (0.53%). Overall, 81% of carcinomas were invasive, and 78% of those were pathologically lymph node-negative tumors, in contrast to the 66% prevalence observed in the Surveillance, Epidemiology, and End Results (SEER) data during the same period. Most invasive tumors measured between 0 mm and 10 mm (35%) or between 11 mm and 20 mm (36%) in greatest dimension, and 92% and 78% were lymph node-negative tumors, respectively: Biopsy results that were classified as malignant increased with age (P < 0.0001) and were most likely to follow Breast Imaging, Reporting, and Diagnosis System Category 5 and 4 assessments, respectively. Ductal hyperplasia (19.6%), fibroadenoma (18.5%), and other benign findings (56.1%) were the most common benign diagnoses. CONCLUSIONS: Pathologically negative lymph nodes were more prevalent in this mammographically screened population than in the overall SEER population. The prevalence of invasive carcinoma, DCIS, and benign findings presented herein establish a range of expected biopsy outcomes for women after screening mammography in the general U.S. population.

Adult↗

PubMed2005

Steroid 5alpha-reductase isozymes I and II in recurrent prostate cancer.

PURPOSE: Prostate cancer recurs during androgen deprivation therapy despite reduced circulating androgens. We showed that recurrent prostate cancer tissue has testosterone levels similar to androgen-stimulated benign prostate, whereas dihydrotestosterone levels were reduced 82% to 1.45 nmol/L, sufficient for androgen receptor activation. The altered testosterone/dihydrotestosterone ratio in recurrent prostate cancer suggests loss of 5alpha-reducing capability. The aim of this study was to characterize steroid 5alpha-reductase isozymes I (S5alphaRI) and II (S5alphaRII) in prostate tissues. EXPERIMENTAL DESIGN: A tissue microarray was constructed from 22 recurrent prostate cancer specimens and matched pairs of androgen-stimulated benign prostate and androgen-stimulated prostate cancer from 23 radical prostatectomy specimens. Immunoblots were constructed from eight recurrent prostate cancers, eight androgen-stimulated benign prostate, and eight androgen-stimulated prostate cancer specimens. Isozyme expression was examined in microarray sections and immunoblots using S5alphaRI and S5alphaRII polyclonal antibodies. Isozyme activities were measured in 12 recurrent prostate cancer, 12 androgen-stimulated benign prostate, and 12 androgen-stimulated prostate cancer specimens. RESULTS: Nuclear immunostaining exhibited higher S5alphaRI expression than S5alphaRII in recurrent prostate cancer, androgen-stimulated benign prostate, and androgen-stimulated prostate cancers (P < 0.0001); mean expression was 125, 150, and 115 for S5alphaRI versus 10, 29, and 37 for S5alphaRII, respectively. Cytoplasmic immunostaining was moderate and similar for both isozymes in the three tissue types (P > 0.05). Immunoblots confirmed immunohistochemistry; S5alphaRI was expressed in recurrent prostate cancer specimens and S5alphaRII was not detected. The activity of S5alphaRI (114.4 pmol/mg epithelial protein/minute) was 3.7-fold higher than S5alphaRII (30.7 pmol/mg epithelial protein/minute) in recurrent prostate cancer specimens. CONCLUSIONS: Expression levels and isozyme activity shifts from S5alphaRII toward S5alphaRI in recurrent prostate cancer. Dual inhibition of S5alphaRI and S5alphaRII should reduce dihydrotestosterone biosynthesis and may prevent or delay growth of recurrent prostate cancer.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed2005

Gleason grading and volume estimation in prostate needle biopsy specimens: evolving issues.

The Gleason grading system for prostate cancer is a powerful tool that can help choose therapy and predict outcome for patients. The clinical use and problem areas of the Gleason grading system are reviewed. The issues discussed include grade discrepancies between prostate biopsy and resection specimens, grading small foci of tumor, diagnosing and grading cribriform lesions, reporting the grade when 3 grades of cancer are present in a specimen, and assignment of grade when multiple cores of differing grades are present. Finally, differing ways of communicating tumor volume and the percentage of high-grade carcinoma in prostate biopsy cores are considered.

Biopsy, Needle↗

PubMed2004

Bronchial margins in lung cancer resection specimens: utility of frozen section and gross evaluation.

Pathology reports for all lobectomy and pneumonectomy specimens at UNC Hospitals between 1991 and 2000 (n=405) were reviewed for correlation between frozen section and final bronchial margin, gross distance between tumor and margin and tumor type. Frozen section was performed in 268 cases (66%). A total of 243 were true negatives (90.6 %), 16 (6.0%) were true positives, four (1.5%) were false positives and five (1.9%) were false negatives. The site of tumor in true-positive cases was mucosal (11), submucosal (three), lymphatics (one), peribronchial (one). The site of tumor in false-negative cases was submucosal (two), lymphatics (one), peribronchial (two). In 137 cases, no bronchial frozen section was performed; there was one case (0.7%) with positive margin. There was no correlation between final margin positivity and distance between gross tumor and margin. Tumor distance to margin in positive margin cases varied from grossly involved to 3 cm away. There were 72 cases in which wedge resection was performed before lobectomy in which no gross tumor remained in the lobectomy, and in all cases final bronchial margins were negative. In all, 373 of cases (92%) were nonsmall carcinomas. Of these, 10 (2.7%) had positive margins. Tumors other than nonsmall cell carcinoma accounted for a disproportionate number of positive margins. In all, 3/6 of adenoid cystic/mucoepidermoid carcinoma, 1/7 small cell carcinoma and 1/1 lymphoma cases had positive margins. In conclusion, frozen section evaluation of bronchial margins is helpful in central lung tumors. Mucosal tumor is preferentially identified in frozen section. Gross evaluation of margins is problematic, as intramucosal carcinoma or tumor in lymphatics may not be detected, but 3 cm was a 'safe' distance for gross tumor from margin. In lobectomies following wedge resection in which no gross tumor remained, all had negative margins. Salivary gland-type tumors have a high incidence of positive margins, and frozen section is particularly indicated in these tumors.

Bronchi↗

PubMed2004

Expression of annexin I, II and VII proteins in androgen stimulated and recurrent prostate cancer.

PURPOSE: We performed a comprehensive survey of annexin I, II and VII protein expression in patient matched benign prostatic epithelium (BPE), androgen stimulated prostate cancer (AS-CaP) and recurrent prostate cancer (R-CaP). MATERIALS AND METHODS: Annexin I, II and VII was immunostained in 23 matched pairs of BPE and AS-CaP specimens, and in 25 R-CaP specimens. Protein expression was assessed visually and using color digital video image analysis. RESULTS: The expression levels of annexins I and II was decreased from BPE to AS-CaP in all patients examined using visual assessment (22 of 22) or digital image analysis (18 of 18 for annexin I and 22 of 22 for annexin II). Annexin I mean optical density (MOD) decreased by 69% (0.718 to 0.222, p <0.0001) and annexin II MOD decreased by 71% (0.820 to 0.238, p <0.0001). Annexin I MOD further decreased almost 50% in R-CaP compared with AS-CaP (0.117 vs 0.222, p <0.0065) and annexin II MOD further declined by 37% (AS-CaP 0.238 vs R-CaP 0.150, p <0.0001). Annexin VII MOD showed no significant change between BPE and AS-CaP (0.229 and 0.214, respectively) but it decreased 14% in R-CaP vs AS-CaP (0.184 vs 0.214, p <0.0051). CONCLUSIONS: Annexins I and II expression are decreased in AS-CaP compared with BPE and a further reduction is observed with progression from AS-CaP to R-CaP. Annexin VII protein expression is decreased in R-CaP, although AS-CaP and BPE are similar. This study suggests that the dysregulations of annexin proteins I, II and VII are important events in prostate carcinogenesis and progression.

Aged↗

PubMed2004

Sampling strategy for prostate tissue microarrays for Ki-67 and androgen receptor biomarkers.

OBJECTIVE: To develop an optimal sampling strategy for tissue microarrays using automated digital analysis for androgen receptor (heterogeneous expression) and the cellular proliferation marker Ki-67 (homogeneous expression and evaluated by others using nonautomated methods). STUDY DESIGN: Tissue microarrays were constructed from 23 radical prostatectomy specimens and immunostained for androgen receptor expression and cellular proliferation. Automated digital image analysis was used, and the minimum number of cores necessary to capture variance change <3% was determined. Androgen receptor immunostaining was described by percent positive nuclei (PPN) and mean optical density (MOD). RESULTS: Androgen receptor PPN variance measurements showed that 5 cores should be obtained when a single block of a radical prostatectomy specimen contained cancer. If all of 15 blocks contained cancer, 2 cores should be obtained from each of 6 blocks. An optimal sampling strategy was developed for androgen receptor PPN, androgen receptor MOD and Ki-67 PPN. CONCLUSION: The selection of the number of cores to sample is a tradeoff between the number of cores available that contain cancer and the amount of work involved in the analysis. Sampling no fewer than 5 but no more than 12 cores per radical prostatectomy specimen can capture tissue heterogeneity.

Aged↗

PubMed2003

Miliary pulmonary metastases from a clinically occult pleural mesothelioma.

Mesothelioma is a rare neoplasm of the serosal membranes. Signs and symptoms of a pleural effusion typically herald discovery of the tumor. We report a case of miliary metastatic mesothelioma involving both lungs in a 54-year-old man who presented with right-sided chest discomfort, numerous pulmonary nodules detected by computed tomography of the chest, and absent pleural effusion. Immunohistochemical and electron microscopy studies performed on wedge biopsies of parenchymal pulmonary nodules led to the diagnosis of metastatic mesothelioma. Subsequent pleural evaluation and biopsy of pleural thickening noted at a site of prior chest wall trauma identified the primary neoplasm and confirmed the diagnosis as malignant epithelioid mesothelioma. The histologic appearance of discohesive epithelioid cells in a distinctly myxoid background was the clue in this case leading to the consideration of metastatic mesothelioma and a thorough immunohistochemical evaluation of the tumor. This case shows that mesothelioma may metastasize throughout the lungs in a miliary pattern and the metastases may be clinically detected before the primary pleural tumor. Metastatic mesothelioma is a consideration for metastatic pulmonary tumors of unknown origin.

Biomarkers, Tumor↗

PubMed2002

Dysregulation of annexin I protein expression in high-grade prostatic intraepithelial neoplasia and prostate cancer.

PURPOSE: To determine expression levels of annexin I (lipocortin I) in patient-matched benign prostatic epithelium (BPE), high-grade prostatic intraepithelial neoplasia (HGPIN), and prostate cancer (CaP). EXPERIMETNAL DESIGN: Annexin I protein expression was examined with a standard immunohistochemical protocol in 69 radical prostatectomy specimens, 45 of which also contained HGPIN. Immunostained sections were scored visually by a genitourinary pathologist and mean optical density was measured with digital image analysis. Real-time fluorescence quantitative PCR was used to measure expression levels of annexin I mRNA in patient-matched CaP and BPE from 14 snap-frozen, radical prostatectomy specimens. RESULTS: Annexin I protein expression was reduced in 91% (41/45) of HGPIN lesions and 94% (65/69) of invasive CaP compared with BPE in the same histological section when assessed visually. Mean absorbance was reduced significantly (P < 0.05) in 97.7% (44/45) of HGPIN lesions and 98.5% (68/69) of CaP glands compared with BPE. In 79% of cases (11/14; P < 0.05), mRNA expression was reduced in CaP as compared with patient-matched BPE. Annexin I mRNA and protein expression levels did not correlate with Gleason grade, pathological stage, or race. CONCLUSIONS: Down-regulation of annexin I protein expression is a common finding in HGPIN and CaP, suggesting that annexin I dysregulation may be an important early event in CaP initiation. Because mRNA levels are reduced in a high proportion of cases, one likely mechanism for annexin I dysregulation occurs at the level of gene transcription. Results of these studies support a valuable role for a molecular profiling approach to CaP research.

Annexin A1↗