PubMed Health⌕ Search

Biomedical subjects

S A Bartow

Publications and source records attributed to S A Bartow.

At least 19 recordsLinked to original sources

Use of the autopsy to study ontogeny and expression of the estrogen receptor gene in human breast.

Historically, autopsies have been a valuable resource for morphologic studies of the human breast, and have been used in conjunction with radiologic evaluation and epidemiology to provide information about population prevalence of pre-malignant and malignant disease. More recently, well-preserved post-mortem breast tissue has also been used to evaluate the status of genes and their expression. Using molecular techniques and immunohistochemistry, quantitation of gene expression and localization of proteins of hormone receptors, growth factor receptors, growth factors, cell-proliferation related antigens and proto-oncogenes can be evaluated in autopsy-derived breast tissue. Expression of the estrogen receptor (ER)3 gene at the mRNA and protein product levels has been evaluated in breast tissue from infants, children, adolescent girls, and adult women in various phases of the menstrual cycle, pregnancy and post-menopausal. The results of these studies support a role for the ER gene in early as well as pubescent breast development, and also in normal cyclical and abnormal cell proliferation in the terminal-duct-lobular-units (TDLU) of adult women.

Adolescent↗

Expression of the estrogen receptor gene in developing and adult human breast.

Although studies of the estrogen receptor gene abound in rodent models and breast cancer cell lines, little is known about expression of this gene in normal human breast. Information regarding the physiology of this gene's expression is important if we are to elucidate abnormalities of the gene that may be involved in breast carcinogenesis. We evaluated levels of mRNA expression of the estrogen receptor (ER) gene and its protein product in a set of 89 breasts from clinically normal female infants, children, adolescents, and adult premenopausal and post-menopausal women. mRNA expression of the gene varied with the hormonal status. Relatively higher levels of gene transcripts were found in breasts of peri-menarchal girls, women in the luteal phase of the menstrual cycle, and in those with fibrocystic change. Higher levels were also occasionally found in breasts of infants and in most pre-adolescent children. Lower levels were seen in breasts of women in the follicular phase of the menstrual cycle, during pregnancy, and after menopause. Nuclear protein staining was common in breasts of normal children and peri-menarchal adolescents, and in post-menopausal atrophic breasts. Nuclear ER protein was infrequently detected in reproductive aged women's breasts, but was more often seen in follicular than in luteal menstrual phase or pregnant breast. ER protein was more frequently seen in post-menopausal than in pre-menopausal breasts with fibrocystic change. The results fit a model in which circulating levels of estrogen are inversely related to levels of mRNA transcribed from the estrogen receptor gene in normal physiologic states. Abnormally high levels of gene transcription may occur in some cases of fibrocystic change.

Adolescent↗

Breast mammographic pattern: a concatenation of confounding and breast cancer risk factors.

A mammographic pattern of > 25% radiodensity is associated with increased risk for breast cancer. Mammographic pattern is influenced by age, body weight, reproductive factors, and race/ethnicity. The interaction among these factors in predicting breast radiographic pattern, and their association with the presence of histologic markers of increased risk of breast cancer, is poorly defined. To elucidate the relations among epidemiologic, radiographic, and histologic markers of breast cancer risk, the authors studied these factors in an unselected forensic autopsy series, accumulated between 1978 and 1983, of 486 women aged 15-98 years at death. Older age and/or postmenopausal status was the strongest predictor of radiolucent breast pattern. Obesity, defined as a Quetelet index (weight(kg)/height(m)2) of > 25, and large breast size were also highly significant predictors of breast radiolucency. Factors related to parity were not significant predictors of breast parenchymal pattern. Native American race was an independent predictor of breast radiolucency in this population. A dense parenchymal pattern was associated with increased prevalence of marked cystic change and the presence of duct epithelial hyperplasia in women under age 35. The results support the association of breast radiodensity with ethnic/racial, reproductive, and histologic factors predictive of cancer risk. However, this association is overshadowed by the effects of obesity and aging or menopause.

Adolescent↗

Epidemiologic and genetic follow-up study of 544 Minnesota breast cancer families: design and methods.

In 1944, a case-control family study was initiated at the Dight Institute for Human Genetics at the University of Minnesota to study the influences of childbearing breastfeeding, and hereditary susceptibility on the occurrence and age-of-onset of breast cancer. Index cases (probands) were women ascertained at the Tumor Clinic of the University of Minnesota Hospital. Medical history and life style information were obtained on probands and relatives, and all cancers were histologically verified. A total of 544 families were studied, with probands diagnosed between 1931 and 1952. All of the records and pathology slides have been maintained from the original study; for most probands this includes the original tissue blocks. We are conducting a historical cohort study of selected of selected first- and second-degree female relatives (sisters, daughters, nieces, granddaughters) of the probands and a group of control women identified as the spouses of all male first- and second-degree relatives (brothers, sons, grandsons, and nephews). The subsequent development of breast cancer is being determined to quantify the absolute risk associated with a positive family history. Current disease status is ascertained with mammography, and stromal density is measured using digital imaging. Segregation analysis will be applied to examine how non-genetic factors such as diet, exogenous hormone use, and body fat distribution influence risk in women at high risk because of family history. A subset of families are being selected for molecular analysis of the BRCA1 gene or for linkage analyses to identify putative susceptibility loci other than BRCA1. Documented cancer histories were known for at least three generations, and the current study extends the pedigrees up to four or five generations for every family, allowing a detailed description of familial risk. This cohort study of breast cancer families is likely to be important in both quantity and quality of data and will serve as a major genetic epidemiologic resource, being free of selection bias and having relevant non-genetic exposure determined in at least four generations.

Adult↗

Distinctive flow histogram pattern in molar pregnancies with elevated maternal serum human chorionic gonadotropin levels.

BACKGROUND: Flow cytometric analysis of trophoblastic tissue has shown that most partial hydatidiform moles (PMs) are triploid, whereas most complete moles (CMs) are diploid or tetraploid. Ploidy analysis can support a diagnosis of CM or PM. However, in some cases, a precise diagnosis cannot be rendered. METHODS: This study examined DNA flow histograms in 86 cases of histologically diagnosed moles and nonmoles to identify patterns specific to moles to eliminate indeterminate diagnoses. Forty hydropic abortions, 17 CMs, and 29 PMs were analyzed, and results were correlated with microscopic appearance and maternal serum human chorionic gonadotropin (HCG) levels. RESULTS: Analysis of nondiploid histologic moles in which the initial maternal serum HCG level was greater than 150,000 mIU/ml showed similar histograms in 12 of 14 cases. In these 12 specimens, a distinct aneuploid peak could not be delineated from multiple cell populations between the G0/G1 and G2/M or G0/G1diploid and G0/G1aneuploid peaks. This commonly appeared as a slope rising toward the tetraploid region. S-phase fraction values showed a trend toward higher values in the moles versus nonmoles, but the difference was not statistically significant. CONCLUSIONS: This sloping histogram pattern may reflect progression from a single aneuploid to multiple aneuploid populations. Its statistically significant correlation (P < 0.001) with high maternal serum HCG values suggests the presence of a highly metabolically active population of aneuploid trophoblast. Because it appears specific to nondiploid moles, recognition of the pattern will aid in the distinction of mole from hydropic spontaneous abortion.

Abortion, Spontaneous↗

Intralobar pulmonary sequestration: a clinical and pathological spectrum.

Pulmonary sequestration is a mass of abnormal pulmonary tissue that does not communicate with the tracheobronchial tree and is supplied by an anomalous systemic artery. Whereas extralobar sequestration is clearly congenital, intralobar sequestration, which frequently presents in older children with pathological findings showing acute and chronic inflammation, may have an acquired origin secondary to frequent infections. Several large autopsy series support an acquired etiology of intralobar sequestration. Four cases of intralobar sequestration are presented that demonstrate a spectrum of inflammatory change that support its congenital, rather than acquired origin. Case 1 was a newborn who presented with tachypnea and a right lower lobe density. Resection at 3 weeks of age showed no inflammation in the sequestration specimen. Case 2 presented as a newborn infant with congestive heart failure. Pulmonary sequestration was confirmed by arteriogram. Resection at 3 months of age showed chronic inflammation. Case 3 presented at 7 months of age with chronic pneumonia. The resected specimen demonstrated moderately severe acute and chronic inflammation. Case 4 presented as a 6 year old. The operative specimen showed extensive bronchiectatic changes with marked acute and chronic inflammation. These cases support the congenital origin of intralobar sequestration and suggest a temporal progression from no inflammation to severe acute and chronic inflammation.

Bronchopulmonary Sequestration↗

Debridement of periumbilical necrotizing fasciitis: importance of excision of the umbilical vessels and urachal remnant.

The operation of a neonate with periumbilical necrotizing fasciitis consisted of (1) excision of infected skin, fat, and fascia (including the umbilicus); (2) a limited laparotomy, with ligation and excision of the umbilical vessels and urachal remnant; and (3) placement of a temporary silastic patch over the central abdominal defect. Pathological sections confirmed the spread of infection along the vessels and urachal remnant. Excision of the vessels and urachal remnant may be crucial to survival from periumbilical necrotizing fasciitis.

Bacterial Infections↗

Aggressive angiomyxoma of the female pelvis and perineum: review of the literature.

Aggressive angiomyxoma is an uncommon neoplasm which predominantly involves the pelvis and perineum of young White females. Misdiagnosis is common. Treatment typically involves surgery, and in spite of apparently complete resection, recurrences are common. Local spread into the adjacent fascia and musculature is frequently reported, and rarely, extension into intestine and bladder. The first reported case of pubic bone involvement, including its histology, radiologic features, and operative management, is discussed. Including this patient, 26 women with this tumor have been reported in the literature and are reviewed, along with 2 previously reported cases from the University of New Mexico Tumor Registry.

Adult↗

Parity factors and prevalence of fibrocystic breast change in a forensic autopsy series.

The relationship of reproductive factors, such as nulliparous vs ever-parous status, age at first birth, and total parity, with morphologic prevalence of fibrocystic changes were examined using autopsy material from three ethnic/racial groups at varying risks for breast cancer. Although there was a trend toward a protective effect of ever-parous status, there was no statistically significant difference in the prevalence of fibrocystic disease in any group defined by parity status. The ethnic differences in the prevalence of fibrocystic changes were not explained by the differences in parity status distribution for the three ethnic/racial groups.

Adolescent↗

Radiographic microcalcification and parenchymal patterns as indicators of histologic "high-risk" benign breast disease.

Breast tissue from a forensic autopsy series of 486 women (15 to 98 years of age) was studied radiographically and by histologic sampling. Prevalence of Wolfe P2/Dy parenchymal patterns decreased with age. Radiographic nonvascular microcalcification and histologic presence of marked ductal epithelial hyperplasia and lobular microcalcification increased with age. Both of these histologic parameters of increased risk for breast cancer correlated with the presence of radiographic microcalcification and Wolfe P2/Dy parenchymal pattern. The predictive value of the radiographic parameters for presence of "high-risk" proliferative fibrocystic change increased with age.

Adolescent↗

Diagnostic and prognostic applications of oncogenes in surgical pathology.

The explosion in basic research and technology associated with oncogenes will undoubtedly have a significant impact on surgical pathology. The techniques of Southern, Northern, and Western blotting along with in situ hybridization and immunohistochemistry are all applicable to the analysis of oncogene status in human solid tumors. The oncogenes imminently affecting surgical pathology practice are those of the ras, myc, HER1-2, and int families, and putative suppressor genes such as the Rb gene. The proto-oncogene counterparts have protein products that normally play key roles in the regulation of cell proliferation, differentiation, and morphogenesis. Qualitative and quantitative alterations of these genes may be associated with the transformation and progression of human solid tumors. The new technology associated with oncogenes must go through a process of assessment to form a bridge between basic research and prudent clinical application. Pathologists should play a key role in this assessment.

Algorithms↗

Age and race related changes in mammographic parenchymal patterns.

The relationship between breast parenchymal patterns and age was examined in a nonselected, nonreferred group. The three major racial-ethnic subgroups represented have markedly different incidences of breast cancer, with Anglos (nonHispanic caucasians), Hispanics, and American Indians having higher to lower incidence rates of breast cancer, respectively. Mammograms were performed in 519 victims of nonhospital, nonnatural or unexplained deaths in New Mexico. The percentage of dense breast patterns (DY + P2) decreased with age for all groups. American Indian women showed a much earlier shift to a lower density parenchymal pattern than Anglo or Hispanic women. At older ages Indian women continued to have a slightly lower percentage of dense breast patterns than the other groups. The changes in breast parenchymal pattern with age and ethnic groups may reflect factors related to risk of breast cancer.

Adolescent↗

DNA flow cytometry in solid tumors: practical aspects and clinical applications.

Investigators are currently using techniques of DNA flow cytometry to measure ploidy status (DNA content) and proliferative potential (S phase fraction) in a wide variety of solid tumors. These measurements have shown relevance for diagnosis, prognosis, and treatment for patients with cancer. National cooperative group studies are beginning to evaluate these measurements in controlled clinical trials to further define their clinical utility as well as limitations. The purpose of this report is to discuss both practical aspects of DNA flow cytometry and clinical applications of these measurements in a variety of solid tumors. We describe in detail our methods for sample handling, processing, and interpretation of DNA histograms. Although there are multiple ways of processing samples and interpreting histograms, we present methodology and interpretations that have proven efficient and reproducible. The review of clinical applications of flow cytometry to solid tumors focuses on breast cancer, but includes a discussion of other solid tumors.

Breast Neoplasms↗

Prevalence of benign, atypical, and malignant breast lesions in populations at different risk for breast cancer. A forensic autopsy study.

A forensic autopsy series of 519 women more than 14 years old was studied for prevalence of benign, atypical, and occult malignant breast lesions. The women included Anglos (non-Hispanic whites), Hispanics, and American Indians from New Mexico and Eastern Arizona. These three ethnic/racial groups are at markedly different risk for the development of breast cancer (Anglo 89 of 100,000 women per year, Hispanic 45.5, and American Indian 24.9. There were striking ethnic/racial and age-related differences in both the prevalence and magnitude of all forms of nonproliferative and proliferative fibrocystic disease. The various subsets of fibrocystic disease were highly associated with each other. Such lesions as apocrine metaplasia, sclerosing adenosis, and lobular microcalcification showed as much difference according to ethnic/racial background and age as the more common cystic change and duct epithelial hyperplasia. Atypical lobular and ductal hyperplasia, carcinoma in situ, and occult invasive carcinoma were uncommon and also occurred in ethnic/racial groups in a pattern that parallels the cancer risk in those groups.

Adenofibroma↗

The New Mexico Melanoma Registry. A model of a statewide cooperative program.

The prevalence of cutaneous melanoma is high among Anglo residents of New Mexico. In order to achieve consistency in diagnosis and pathologic staging, a melanoma registry was established in 1980 in conjunction with the University of New Mexico Cancer Center. The registry functions through pathology panel review of newly diagnosed melanomas combined with collection of clinical data. Reports are submitted gratis to contributing pathologists and dermatologists. The melanoma registry works closely with the population-based New Mexico Tumor Registry. Acceptance of the melanoma registry has been excellent. We believe that in excess of 90% of new melanoma cases in the state are sent spontaneously to the registry. During 1986 approximately 150 melanomas were reviewed together with 450 atypical, benign pigmented lesions such as dysplastic nevi. In addition to pathology consultations, the registry serves an educational function and has potential for a variety of epidemiologic studies.

Data Display↗

Occult breast cancer: prevalence and radiographic detectability.

The radiographic detectability of occult breast cancer has been difficult to determine. A prospective study of breast disease was carried out that involved the performance of subcutaneous mastectomies in 519 consecutive cases of traumatic or initially unexplained death in New Mexico. Routine mammograms and radiographs of 1-cm specimens were obtained. At least 18 biopsies were performed in each subject. Carcinoma was identified in ten subjects; one subject had metastatic carcinoma from the lung, and two subjects had bilateral breast cancer, for a total of 11 breast cancers identified with microscopic examination. Two of the cancers were seen on whole-breast mammograms, and six were seen on radiographs of thin-section specimens. Four of the 11 breast cancers were apparent only on histologic study of breast tissue that was not suggestive of malignancy. No cancer was found in subjects under the age of 39 years. Five carcinomas were found in the 40-69-year age group; six were found in the 70-year and over age group. No correlation was noted between the radiographic Wolfe parenchymal patterns and the prevalence of breast cancer.

Adolescent↗

Oncogenes and surgical pathology.

The discovery of oncogenes began with identification of genetic material in viruses capable of causing neoplasia in animals. Through processes of "transduction" and "insertional mutagenesis," RNA/retroviruses may (1) alter directly, (2) alter expression of, or (3) move pieces of host cellular genome in ways that they become potential agents of neoplastic transformation. The pieces of host cellular genome, either affected in situ by viral gene insertion or transduced by the virus, are known as oncogenes. Approximately 20 oncogenes have been identified. Although they have yet to be proven to be sufficient or necessary for neoplastic transformation, the evidence for their playing a part in the transformation process is mounting. The functions of the protein products of the various oncogenes are closely related to those of proteins involved in normal cell regulatory and cycle activities. Study of the oncogene products and their functions serves to elucidate the basic character of neoplasia. The functional classes of oncogenes with specific examples of genomic amplification, altered mRNA or protein product expression, or mutational deletion associated with human neoplasia are reviewed herein. Since the techniques for detecting oncogene DNA and mRNA alterations are rapidly becoming a part of our diagnostic armamentarium, surgical pathologists should be prepared for the imminent use of such molecular techniques and information in diagnosis and prognosis of human neoplasia.

Cell Transformation, Neoplastic↗