Primary primitive neuroectodermal tumor of the breast.
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Adult↗
Biomedical subjects
Rex C Bentley
Publications and source records attributed to Rex C Bentley.
Genetic modeling of human rhabdomyosarcoma.
Rhabdomyosarcoma, a malignancy showing features of skeletal muscle differentiation, is the most common soft tissue sarcoma of childhood. The identification of distinct clinical presentation patterns, histologic tumor types, and risk groups suggests that rhabdomyosarcoma is a collection of highly related sarcomas rather than a single entity. In an effort to understand this seemingly heterogeneous malignancy, we constructed a genetically defined but malleable model of rhabdomyosarcoma by converting less differentiated human skeletal muscle cell precursors (SkMC) and committed human skeletal muscle myoblasts (HSMM) into their malignant counterparts by targeting pathways altered in rhabdomyosarcoma. Whereas the two cell types were both tumorigenic, SkMCs gave rise to highly heterogeneous tumors occasionally displaying features of rhabdomyosarcoma, whereas HSMMs formed rhabdomyosarcoma-like tumors with an embryonal morphology, capable of invasion and metastasis. Thus, despite introducing the same panel of genetic changes, altering the skeletal muscle cell of origin led to different tumor morphologies, suggesting that cell of origin may dictate rhabdomyosarcoma tumor histology. The ability to now genetically induce human rhabdomyosarcoma-like tumors provides a representative model to dissect the molecular mechanisms underlying this cancer.
Adolescent↗
Anthropometric measurements and epithelial ovarian cancer risk in African-American and White women.
Previous studies of anthropometric factors and ovarian cancer risk have been inconsistent and none have evaluated the association among African-American women. Data from a population-based, case-control study of 593 cases and 628 controls were used to evaluate ovarian cancer risk in relation to weight, height, body mass index (BMI) and waist-to-hip ratio (WHR). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed and established risk factors were adjusted for using logistic regression models, stratified by race. Among all races, weight at age 18, WHR, weight and BMI one year prior to interview were associated with elevated ovarian cancer risk. When stratified by race, the association between WHR and ovarian was similar among Whites and among African Americans. However, African-American women in the fourth quartile of height had an elevated risk of ovarian cancer (OR = 3.2; 95% CI = 1.3-7.8), but this risk was not apparent in Whites (OR = 1.0; 95% CI = 0.7-1.4). These findings support the hypothesis that obesity is an important risk factor of ovarian cancer among African-Americans and Whites and also suggest that height may be a risk factor specific to African-Americans.
Adult↗
Transforming growth factor beta receptor I polyalanine repeat polymorphism does not increase ovarian cancer risk.
OBJECTIVES: It has been suggested that the 6A allele of the type I TGFbeta receptor (TGFbetaR1) polyalanine repeat tract polymorphism may increase susceptibility to various types of cancer including ovarian cancer. METHODS: The TGFbetaR1 polyalanine polymorphism was genotyped in 588 ovarian cancer cases and 614 controls from a population-based case-control study in North Carolina. RESULTS: Significant racial differences in the frequency of the 6A allele were observed between Caucasian (10.7%) and African-American (2.4%) controls (P < 0.001). One or two copies of the 6A allele of the TGFbetaR1 polyalanine polymorphism was carried by 18% of all controls and 19% of cases, and there was no association with ovarian cancer risk (OR = 1.07, 95% CI 0.80-1.44). The odds ratio for 6A homozygotes was 1.81 (95% CI 0.655.06), but these comprised only 0.98% of controls and 1.70% of cases. CONCLUSIONS: The 6A allele of the TGFbetaR1 polyalanine polymorphism does not appear to increase ovarian cancer risk. Larger studies would be needed to exclude the possibility that the small fraction of individuals who are 6A homozygotes have an increased risk of ovarian or other cancers.
Adult↗
Acoustic radiation force impulse (ARFI) imaging of the gastrointestinal tract.
The evaluation of lesions in the gastrointestinal (GI) tract using ultrasound can suffer from poor contrast between healthy and diseased tissue. Acoustic Radiation Force Impulse (ARFI) imaging provides information about the mechanical properties of tissue using brief, high-intensity, focused ultrasound to generate radiation force and ultrasonic correlation-based methods to track the resulting tissue displacement. Using conventional linear arrays, ARFI imaging has shown improved contrast over B-mode images when applied to solid masses in the breast and liver. The purpose of this work is to (1) investigate the potential for ARFI imaging to provide improvements over conventional B-mode imaging of GI lesions and (2) demonstrate that ARFI imaging can be performed with an endocavity probe. ARFI images of an adenocarcinoma of the gastroesophageal (GE) junction, status-post chemotherapy and radiation treatment, demonstrate better contrast between healthy and fibrotic/malignant tissue than standard B-mode images. ARFI images of healthy gastric, esophageal, and colonic tissue specimens differentiate normal anatomic tissue layers (i.e., mucosal, muscularis and adventitial layers), as confirmed by histologic evaluation. ARFI imaging of ex vivo colon and small bowel tumors portray interesting contrast and structure that are not as well defined in B-mode images. An endocavity probe created ARFI images to a depth of over 2 cm in tissue-mimicking phantoms, with maximum displacements of 4 microm. These findings support the clinical feasibility of endocavity ARFI imaging to guide diagnosis and staging of disease processes in the GI tract.
Adenocarcinoma↗
Estrogen receptor alpha (ESR1) mutant A908G is not a common feature in benign and malignant proliferations of the breast.
Alterations in estrogen responsive pathways are thought to contribute to benign and malignant breast disease. It has been reported previously that more than a third of typical epithelial hyperplasia lesions harbor the missense mutation A908G in the estrogen receptor alpha (ESR1) gene. This substitution of an arginine for a lysine at codon 303 was reported to confer mitogenic hypersensitivity to estrogen. To explore this finding further, we analyzed ESR1 for this mutation in a series of breast tissues ranging from typical hyperplasia to invasive cancer. In contrast to previous studies, no evidence for this mutation was found in 36 invasive cancers, 11 in situ carcinomas, 14 epithelial hyperplasias with atypia, 11 epithelial hyperplasias without atypia, and 11 breast cancer cell lines. These results indicate that ESR1 mutant A908G does not occur with significant frequency in either benign or malignant proliferations of breast epithelia.
Base Sequence↗
Acoustic radiation force impulse imaging of the mechanical properties of arteries: in vivo and ex vivo results.
We present results of a pilot study of ex vivo and in vivo acoustic radiation force impulse (ARFI) imaging demonstrating measurements of the mechanical properties of the carotid and popliteal arteries. The results were obtained on a modified commercial scanner, providing coregistered B-mode and color Doppler images. 2D and 1D through time images are formed from the measurements of tissues' response to very brief and localized applications of radiation force. The images show good correlation with B-mode and, in ex vivo studies, pathology-based characterizations of vessel geometry and plaque stiffness. In vivo measurements of arterial response during both systole and diastole are presented. We address implementation issues and discuss potential applications of this new vascular imaging method.
Biomechanical Phenomena↗
Radical hysterectomy and pelvic lymphadenectomy for stage IB2 cervical cancer.
OBJECTIVE: We wished to evaluate survival and adverse outcomes of patients with stage IB2 cervical cancer treated primarily with radical hysterectomy and lymphadenectomy. METHODS: A review was performed of all patients undergoing primary radical hysterectomy for stage IB2 cervical cancer at two institutions from 1987 to 2002. Patients were stratified into low, intermediate (Gynecologic Oncology Group protocol 92 criteria), and high-risk (positive nodes, margins, or parametria) groups. Survival and progression-free interval were analyzed using the Kaplan-Meier method and multivariate analysis. RESULTS: Seventy-two patients underwent primary type III radical hysterectomy and lymphadenectomy (72 pelvic, 58 pelvic and paraaortic). Patients were classified as low (n = 6), intermediate (n = 49), or high (n = 17) risk for recurrence. Adjuvant therapy was administered to 94%, 12%, and 0% of the high-, intermediate-, and low-risk groups, respectively. Five-year survival was 72%, while 5-year progression-free survival was 63%. Five-year overall and progression-free survival by risk group were 47% and 40% (high-risk), 80% and 66% (intermediate-risk), 100% and 100% (low-risk). Predictors of survival in multivariate analysis were Caucasian race (P = 0.001), older age (P = 0.017), inner 2/3 cervical wall invasion (P = 0.045), and absence of lymph-vascular invasion (P < 0.001). Major complications were experienced by 10/72 (13.9%) patients. Among 34 patients who received radiation therapy, two (5.9%) experienced complications attributable to radiation. CONCLUSIONS: Radical hysterectomy and lymphadenectomy followed by tailored adjuvant therapy is a reasonable alternative to primary radiotherapy for stage IB2 cervical cancer. Patients with low- and intermediate-risk factors have satisfactory results after primary surgical management. A prospective randomized trial will clarify the optimal mode of initial therapy for patients with stage IB2 disease.
Adult↗
Polymorphisms in BRCA1 and BRCA2 and risk of epithelial ovarian cancer.
PURPOSE: Because inherited BRCA1 or BRCA2 mutations strikingly increase ovarian cancer risk, polymorphisms in these genes could represent low penetrance susceptibility alleles. Previous studies of the BRCA2 N372H polymorphism suggested that HH homozygotes have a modestly increased risk of both breast and ovarian cancer. We have examined whether BRCA2 N372H or common amino acid-changing polymorphisms in BRCA1 predispose to ovarian cancer. EXPERIMENTAL DESIGN: A population-based, case control study of ovarian cancer was performed in North Carolina. Cases included 312 women with ovarian cancer (76% invasive and 24% borderline) and 401 age- and race-matched controls. Blood DNA from subjects was genotyped for BRCA2 N372H and BRCA1 Q356R and P871L. RESULTS: There was no association between BRCA2 N372H and risk of borderline or invasive epithelial ovarian cancer. The overall odds ratio (OR) for HH homozygotes was 0.8 [95% confidence interval (CI) = 0.4-1.5] and was similar in all subsets, including invasive serous cases. In addition, neither the BRCA1 Q356R (OR = 0.9, 95% CI 0.5-1.4) nor P871L (OR = 0.9, 95% CI 0.6-1.9) polymorphisms were associated with ovarian cancer risk. There was a significant racial difference in allele frequencies of the P871L polymorphism (P = 0.64 in Caucasians, L = 0.76 in African-Americans, P < 0.0001). CONCLUSIONS: In this population-based, case control study, common amino acid changing BRCA1 and 2 polymorphisms were not found to affect the risk of developing ovarian cancer.
Adenocarcinoma, Clear Cell↗
Pathology of gestational trophoblastic disease.
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Choriocarcinoma↗
Accuracy of MRI in the detection of residual breast cancer after neoadjuvant chemotherapy.
OBJECTIVE: This study was undertaken to evaluate the ability of MRI to accurately show residual primary breast malignancy in women treated with neoadjuvant chemotherapy. MATERIALS AND METHODS: Twenty-one patients with locally advanced primary breast carcinoma underwent contrast-enhanced MRI before and after treatment with neoadjuvant anthracycline-based chemotherapy. For each patient, the maximum extent of the MRI abnormality was measured both before and after treatment. These measurements were subsequently compared with physical examination findings and histologic results to determine the ability of MRI to accurately reveal tumor extent after neoadjuvant chemotherapy. RESULTS: MRI after chemotherapy showed a correlation coefficient of 0.75 with histology, which was better than physical examination (r = 0.61). MRI underestimated the extent of residual tumor in two patients by more than 1 cm (including one false-negative examination), was within 1 cm in 12 of 21 patients, and overestimated tumor extent by more than 1 cm in seven of 21 patients. CONCLUSION: MRI can show residual malignancy after neoadjuvant chemotherapy better than physical examination, particularly in patients who have not had a complete clinical response to therapy.
Adult↗
Increased sectioning of pathologic specimens with ductal carcinoma in situ of the breast: are there clinical consequences?
To assess if there has been increased sectioning of pathologic specimens with ductal carcinoma in situ (DCIS), identify sources of this change, and consider the clinical consequences, pathologic data from patients who underwent initial excisional biopsies at our institution and were referred to the radiation oncology department with DCIS from 1992-2002 were retrospectively reviewed. One hundred forty-four of 480 patients with DCIS were eligible for review. Specimen size was recorded as length, to the nearest 0.1 cm, in 3 dimensions. Specimen volume was approximated by the product of the 3 dimensions of the specimen. The primary endpoint was the number of microscopic sections taken from gross specimens, corrected for specimen size. Other analysis included margin status, use of a previous stereotactic needle biopsy, and whether a subsequent repeat excision was performed. Over time, there was an increase in size of the excisional biopsy specimens (mean of 49 cm3 from 1992 to 1994 and 90 cm3 from 2001 to 2002; P = 0.045). Mean numbers of slides per centimeter of specimen were 2.5, 2.7, 3.9, and 5.8 for the intervals 1992-1994, 1995-1997, 1998-2000, and 2001-2002, respectively (P < 0.001 for 1992-1997 vs. 1998-2002). Adjusting for volume, the increase over time in the number of slides per specimen was statistically significant (parameter significance, P < 0.001). For a given volume, the number of slides increased approximately 9.1% per year, on average, during the study period. The positive margin rates were 52%, 46%, 23%, and 25% from 1992 to 1994, from 1995 to 1997, from 1998 to 2000, and from 2001 to 2002, respectively. The degree of sectioning, corrected for specimen length and volume, increased over time.
Biopsy↗
No relationship between ovarian cancer risk and progesterone receptor gene polymorphism in a population-based, case-control study in North Carolina.
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Adult↗
Progestin-induced apoptosis in the Macaque ovarian epithelium: differential regulation of transforming growth factor-beta.
BACKGROUND: Oral contraceptive (OC) use is associated with a reduced risk of ovarian cancer. An OC component, progestin, induces apoptosis in the primate ovarian epithelium. One regulator of apoptosis is transforming growth factor-beta (TGF-beta). We determined the effect of progestin on TGF-beta expression in the primate ovarian epithelium and examined the relationship between TGF-beta expression and apoptosis. METHODS: Female cynomolgus macaques were randomly assigned to receive a diet for 35 months containing no hormones (n = 20); the OC Triphasil (n = 17); or each of its constituents, ethinyl estradiol (estrogen, n = 20) or levonorgestrel (progestin, n = 18 ), alone. Ovarian sections were immunostained with monoclonal antibodies against TGF-beta1 or TGF-beta2 plus TGF-beta3 (TGF-beta2/3) isoforms. The expression of TGF-beta isoforms in four ovarian compartments (epithelium, oocytes, granulosa cells, and hilar vascular endothelium) was compared among treatment groups. The association between TGF-beta expression and apoptosis, as determined by morphology and histochemistry, was examined in ovarian epithelium. All statistical tests were two-sided. RESULTS: Compared with ovaries from the control and estrogen-only-treated monkeys, the ovaries of progestin-treated monkeys showed 1) a marked decrease in the expression of TGF-beta1 and a concomitant increase in the expression of the TGF-beta2/3 isoforms in the ovarian epithelium (P<.001), 2) an increase in the expression of TGF-beta2/3 in the hilar vascular endothelium (P<.001), and 3) a marked decrease in TGF-beta2/3 expression in granulosa cells (P<.001). The apoptotic index of the ovarian epithelium was highly associated with the change in expression from TGF-beta1 (P<.001) to TGF-beta2/3 (P</=.002) induced by progestin treatment. CONCLUSIONS: Progestin induces differential regulation in the ovarian epithelium of TGF-beta, a change in the expression of which is highly associated with apoptosis. These data suggest a possible biologic mechanism for the protective association between OC use and reduced ovarian cancer risk.
Animals↗
Imaging-guided core needle biopsy of papillary lesions of the breast.
OBJECTIVE: Our objective was to assess the incidence of papillary lesions of the breast diagnosed at imaging-guided core needle biopsy and the need for surgical excision after a benign diagnosis. MATERIALS AND METHODS: This retrospective study included 1374 patients with consecutive suspicious breast lesions that underwent either mammography or sonographically guided large-core needle breast biopsy. Fifty-seven lesions (4%) were classified as papillary lesions. Eleven of the 57 cases were lost to follow-up (n = 6) or had not yet shown 2 years of stability (n = 5) and were excluded from this study. The remaining 46 papillary lesions constitute our study population. RESULTS: Surgical excision was performed in 17 (37%) of 46 papillary lesions. In the group of patients whose lesions were recommended for excision because carcinoma was identified at core biopsy, surgical excision revealed one false-positive and two true-positive diagnoses. In four cases, histologic diagnoses of the excisional biopsy and the core needle biopsy were discordant. One false-positive finding at core needle biopsy initially was interpreted as invasive ductal carcinoma on the basis of core needle biopsy specimens. In three false-negative findings, the initial diagnosis at core needle biopsy was upgraded after surgical excision. Two cases of papilloma with adjacent atypical ductal hyperplasia and one of atypical papilloma were upgraded to ductal carcinoma in situ after surgical excision. Imaging follow-up was performed in the remaining 29 patients. All lesions were stable or had decreased in size during the 2-year follow-up period. The negative predictive value of core needle biopsy for excluding malignancy among the papillary lesions diagnosed in our study was 93%. CONCLUSION: When the histologic diagnosis is benign, our data suggest that papillary lesions may be safely managed with imaging follow-up rather than with surgical excision. However, atypical papillary lesions or those associated with atypia require surgical excision because histologic underestimation occurs at a frequency similar to that in other atypical lesions undergoing core needle biopsy.
Biopsy, Needle↗